{Linking permeability and mechanical damage for basalt from Mt Etna Volcano, Italy}

NASA Astrophysics Data System (ADS)

Faoro, I.; Vinciguerra, S.; Marone, C.; Elsworth, D.

2009-04-01

Volcanic edifices, such as Mt. Etna volcano (Italy), are affected from repeated episodes of pressurisation due to magma emplacement from deep reservoirs to shallow depths. This mechanism pressurizes the large aquifers within the edifice and increases the level of crack damage within the rocks of the edifice over extended periods of times. In order to improve our understanding of the complex coupling between circulating fluids and the development of crack damage, we performed flow-through tests using cylindrical cores of Etna Basalt (Etna, Italy) to evaluate permeabilty changes as a function of approach to failure under non-hydrostatic stresses at confining pressures from 5 to 60 MPa. Samples were loaded to failure by increasing increments of axial stress or by cyclic stresses of increasing amplitude. Both intact samples and pre-drilled samples (1.18mm) were tested. Under hydrostatic stresses, the permeability values of the intact sample decrease linearly with the increments of pressure and range between 5.2*10-17 m2and 1.5*10-17m2Under non-hydrostatic conditions, at low deviatoric stresses from (up to 18 MPa), the permeability values ranged between 5.5*10-17 m2and 4*10-17m2 and tended to completely recover the initial value each time the sample was unloaded, indicating an elastic regime. At higher deviatoric stresses (up to 60 MPa) the permeability values range between 2*10-17 m2 and 0.6*10-17m2. We hypothesize that from 5MPa to 40MPa axial stress, anelastic deformation mechanisms start to occur, with progressive pore collapse and opening of microfractures, resulting in a change of permeability. Under incremental uniaxial cyclic loading up to peak stresses of 160 MPa permeability decreases up to 2 orders of magnitude from initial values of 1*10-15 m2 to 2*10-14m2 Higher initial permeability values are related to the presence of an open fracture in the sample. We interpreted the reduction as a result of progressive closure of the voids space, as the axial load is incremented. Overall it is shown that permeability on Etna basalt rocks is strongly dependent on the loading conditions. Ongoing work is expected to elucidate the mechanisms relating increasing damage mechanical damage to changes of permeability.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Quantifying progression and regression of thrombotic risk in experimental atherosclerosis.

PubMed

Palekar, Rohun U; Jallouk, Andrew P; Goette, Matthew J; Chen, Junjie; Myerson, Jacob W; Allen, John S; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J; Pham, Christine T N; Wickline, Samuel A; Pan, Hua

2015-07-01

Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200-300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [(19)F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy. © FASEB.

Abnormal permeability of inner and outer mitochondrial membranes contributes independently to mitochondrial dysfunction in the liver during acute endotoxemia.

PubMed

Crouser, Elliott D; Julian, Mark W; Huff, Jennifer E; Joshi, Mandar S; Bauer, John A; Gadd, Martha E; Wewers, Mark D; Pfeiffer, Douglas R

2004-02-01

This study was designed to determine the role played by the mitochondrial permeability transition in the pathogenesis of mitochondrial damage and dysfunction in a representative systemic organ during the acute phase of endotoxemia. A well-established, normotensive feline model was employed to determine whether pretreatment with cyclosporine A, a potent inhibitor of the mitochondrial permeability transition, normalizes mitochondrial ultrastructural injury and dysfunction in the liver during acute endotoxemia. The Ohio State University Medical Center research laboratory. Random source, adult, male conditioned cats. Hemodynamic resuscitation and maintenance of acid-base balance and tissue oxygen availability were provided, as needed, to minimize the potentially confounding effects of tissue hypoxia and/or acidosis on the experimental results. Treatment groups received isotonic saline vehicle (control; n = 6), lipopolysaccharide (3.0 mg/kg, intravenously; n = 8), or cyclosporine A (6.0 mg/kg, intravenously; n = 6) or tacrolimus (FK506, 0.1 mg/kg, intravenously; n = 4) followed in 30 mins by lipopolysaccharide (3.0 mg/kg, intravenously). Liver samples were obtained 4 hrs posttreatment, and mitochondrial ultrastructure, function, and cytochrome c, Bax, and ceramide contents were assessed. As expected, significant mitochondrial injury was apparent in the liver 4 hrs after lipopolysaccharide treatment, despite maintenance of regional tissue oxygen availability. Namely, mitochondria demonstrated high-amplitude swelling and exhibited altered respiratory function. Cyclosporine A pretreatment attenuated lipopolysaccharide-induced mitochondrial ultrastructural abnormalities and normalized mitochondrial respiratory control, reflecting protection against inner mitochondrial membrane damage. However, an abnormal permeability of outer mitochondrial membranes to cytochrome c was observed in all lipopolysaccharide-treated groups and was associated with increased mitochondrial concentrations of Bax and ceramide. These studies confirm that liver mitochondria are early targets of injury during endotoxemia and that inner and outer mitochondrial membrane damage occurs through different mechanisms. Inner mitochondrial membrane damage appears to relate to the mitochondrial permeability transition, whereas outer mitochondrial membrane damage can occur independent of the mitochondrial permeability transition. Preliminary evidence suggests that Bax may participate in lipopolysaccharide-induced outer mitochondrial membrane damage, but further investigations are needed to confirm this.

Hydromechanical behavior of Estaillades carbonate : directional permeability, stress-path and microstructural heterogeneity effects, yield and failure envelopes

NASA Astrophysics Data System (ADS)

Dautriat, J.; Dimanov, A.; Gland, N.; Raphanel, J.

2009-04-01

The influence of stress paths representative of reservoir conditions on the mechanical behavior and the coupled permeability evolutions of a carbonate has been investigated. In order to predict the permeability evolutions under triaxial loading, we have developed a triaxial cell designed to allow the measurements of the permeability in three orthogonal directions, along and transverse to the maximum principal stress direction. A set of core specimens are mechanically loaded following different stress paths characterized by a constant ratio K between horizontal and vertical stress. Our experimental set-up allows the monitoring of the petrophysical and geomechanical parameters during loading, before and post sample damage. The tested rock is an analog reservoir carbonate, the Estaillades Limestone, characterized macroscopically by a porosity around 29% and a moderate permeability around 150mD. From our experimental results, the failure envelope of this carbonate is determined and the evolutions of the directional permeability are examined in the (p',q) diagram. According to the followed stress path, permeability reductions can be limited or drastic. In addition, we have performed microstructural analyses on deformed samples and in-situ observations during loading inside a SEM in order to identify the micromechanisms responsible for the evolutions of porosity and permeability. For instance, we show the importance of local heterogeneities on initiation of damage and of pore collapse. In the near-elastic domain, brittle damage induces limited directional permeability modifications; whereas, at higher stress, depending on the value of K, shear induced dilation or shear induced compaction mechanisms are activated. The highest permeability drop occurred for the hydrostatic compression (K=1), in the compaction regime, characterized by pore collapse mechanisms affecting preferentially the macroporosity. A failure model is proposed and the failure envelope is determined in the (p',q) plane. A new expression of the failure envelope is also discussed which includes a dependency of the deviatoric stress with the stress-path parameter.

Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism.

PubMed

Leite, A Z; Sipahi, A M; Damião, A O; Coelho, A M; Garcez, A T; Machado, M C; Buchpiguel, C A; Lopasso, F P; Lordello, M L; Agostinho, C L; Laudanna, A A

2001-02-01

The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested. To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage. The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline. Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate. Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.

Numerical Simulation of Hydraulic Fracturing in Low-/High-Permeability, Quasi-Brittle and Heterogeneous Rocks

NASA Astrophysics Data System (ADS)

Pakzad, R.; Wang, S. Y.; Sloan, S. W.

2018-04-01

In this study, an elastic-brittle-damage constitutive model was incorporated into the coupled fluid/solid analysis of ABAQUS to iteratively calculate the equilibrium effective stress of Biot's theory of consolidation. The Young's modulus, strength and permeability parameter of the material were randomly assigned to the representative volume elements of finite element models following the Weibull distribution function. The hydraulic conductivity of elements was associated with their hydrostatic effective stress and damage level. The steady-state permeability test results for sandstone specimens under different triaxial loading conditions were reproduced by employing the same set of material parameters in coupled transient flow/stress analyses of plane-strain models, thereby indicating the reliability of the numerical model. The influence of heterogeneity on the failure response and the absolute permeability was investigated, and the post-peak permeability was found to decrease with the heterogeneity level in the coupled analysis with transient flow. The proposed model was applied to the plane-strain simulation of the fluid pressurization of a cavity within a large-scale block under different conditions. Regardless of the heterogeneity level, the hydraulically driven fractures propagated perpendicular to the minimum principal far-field stress direction for high-permeability models under anisotropic far-field stress conditions. Scattered damage elements appeared in the models with higher degrees of heterogeneity. The partially saturated areas around propagating fractures were simulated by relating the saturation degree to the negative pore pressure in low-permeability blocks under high pressure. By replicating previously reported trends in the fracture initiation and breakdown pressure for different pressurization rates and hydraulic conductivities, the results showed that the proposed model for hydraulic fracture problems is reliable for a wide range of pressurization rates and permeability conditions.

Membrane permeability and the loss of germination factor from Neurospora crassa at low water activities

NASA Technical Reports Server (NTRS)

Charlang, G.; Horowitz, N. H.

1974-01-01

Neurospora crassa conidia incubating in buffer at low water activities release a germination-essential component as well as 260-nm absorbing and ninhydrin-positive materials, regardless of whether an electrolyte or nonelectrolyte is used to reduce water activity. Chloroform and antibiotics known to increase cell-membrane permeability have a similar effect. This suggests that membrane damage occurs in media of low water activity and that an increase in permeability is responsible for the release of cellular components. The damage caused in media of low water activity is nonlethal in most cases, and the conidia recover when transferred to nutrient medium.

Estimating retinal vascular permeability using the adiabatic approximation to the tissue homogeneity model with fluorescein videoangiography

NASA Astrophysics Data System (ADS)

Tichauer, Kenneth M.; Osswald, Christian R.; Dosmar, Emily; Guthrie, Micah J.; Hones, Logan; Sinha, Lagnojita; Xu, Xiaochun; Mieler, William F.; St. Lawrence, Keith; Kang-Mieler, Jennifer J.

2015-06-01

Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today's treatment standards. As a result, there is a push to develop new, "sub-clinical" methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.

Geometry of the Nojima fault at Nojima-Hirabayashi, Japan - I. A simple damage structure inferred from borehole core permeability

USGS Publications Warehouse

Lockner, David A.; Tanaka, Hidemi; Ito, Hisao; Ikeda, Ryuji; Omura, Kentaro; Naka, Hisanobu

2009-01-01

The 1995 Kobe (Hyogo-ken Nanbu) earthquake, M = 7.2, ruptured the Nojima fault in southwest Japan. We have studied core samples taken from two scientific drillholes that crossed the fault zone SW of the epicentral region on Awaji Island. The shallower hole, drilled by the Geological Survey of Japan (GSJ), was started 75 m to the SE of the surface trace of the Nojima fault and crossed the fault at a depth of 624 m. A deeper hole, drilled by the National Research Institute for Earth Science and Disaster Prevention (NIED) was started 302 m to the SE of the fault and crossed fault strands below a depth of 1140 m. We have measured strength and matrix permeability of core samples taken from these two drillholes. We find a strong correlation between permeability and proximity to the fault zone shear axes. The half-width of the high permeability zone (approximately 15 to 25 m) is in good agreement with the fault zone width inferred from trapped seismic wave analysis and other evidence. The fault zone core or shear axis contains clays with permeabilities of approximately 0.1 to 1 microdarcy at 50 MPa effective confining pressure (10 to 30 microdarcy at in situ pressures). Within a few meters of the fault zone core, the rock is highly fractured but has sustained little net shear. Matrix permeability of this zone is approximately 30 to 60 microdarcy at 50 MPa effective confining pressure (300 to 1000 microdarcy at in situ pressures). Outside this damage zone, matrix permeability drops below 0.01 microdarcy. The clay-rich core material has the lowest strength with a coefficient of friction of approximately 0.55. Shear strength increases with distance from the shear axis. These permeability and strength observations reveal a simple fault zone structure with a relatively weak fine-grained core surrounded by a damage zone of fractured rock. In this case, the damage zone will act as a high-permeability conduit for vertical and horizontal flow in the plane of the fault. The fine-grained core region, however, will impede fluid flow across the fault.

Doxycycline Attenuates Lipopolysaccharide-Induced Microvascular Endothelial Cell Derangements.

PubMed

Wiggins-Dohlvik, Katie; Stagg, Hayden W; Han, Min Suk; Alluri, Himakarnika; Oakley, Ryan P; Anasooya Shaji, Chinchusha; Davis, Matthew L; Tharakan, Binu

2016-06-01

Lipopolysaccharide (LPS) is known to induce vascular derangements. The pathophysiology involved therein is unknown, but matrix metalloproteinases (MMPs) may be an important mediator. We hypothesized that in vitro LPS provokes vascular permeability, damages endothelial structural proteins, and increases MMP activity; that in vivo LPS increases permeability and fluid requirements; and that the MMP inhibitor doxycycline mitigates such changes. Rat lung microvascular endothelial cells were divided into four groups: control, LPS, LPS plus doxycycline, and doxycycline. Permeability, structural proteins β-catenin and Filamentous-actin, and MMP-9 activity were examined. Sprauge Dawley rats were divided into sham, IV LPS, and IV LPS plus IV doxycycline groups. Mesenteric postcapillary venules were observed. Blood pressure was measured as animals were resuscitated and fluid requirements were compared. Statistical analysis was conducted using Student's t-test and ANOVA. In vitro LPS increased permeability, damaged adherens junctions, induced actin stress fiber formation, and increased MMP-9 enzyme activity. In vivo, IV LPS administration induced vascular permeability. During resuscitation, significantly more fluid was necessary to maintain normotension in the IV LPS group. Doxycycline mitigated all derangements observed. We conclude that LPS increases permeability, damages structural proteins, and increases MMP-9 activity in endothelial cells. Additionally, endotoxemia induces hyperpermeability and increases the amount of IV fluid required to maintain normotension in vivo. Doxycycline mitigates such changes both in vitro and in vivo. Our findings illuminate the possible role of matrix metalloproteinases in the pathophysiology of lipopolysaccharide-induced microvascular hyperpermeability and pave the way for better understanding and treatment of this process.

Three-dimensional analysis of a faulted CO 2 reservoir using an Eshelby-Mori-Tanaka approach to rock elastic properties and fault permeability

DOE PAGES

Nguyen, Ba Nghiep; Hou, Zhangshuan; Last, George V.; ...

2016-09-29

This work develops a three-dimensional multiscale model to analyze a complex CO 2 faulted reservoir that includes some key geological features of the San Andreas and nearby faults southwest of the Kimberlina site. The model uses the STOMP-CO 2 code for flow modeling that is coupled to the ABAQUS® finite element package for geomechanical analysis. A 3D ABAQUS® finite element model is developed that contains a large number of 3D solid elements with two nearly parallel faults whose damage zones and cores are discretized using the same continuum elements. Five zones with different mineral compositions are considered: shale, sandstone, faultmore » damaged sandstone, fault damaged shale, and fault core. Rocks’ elastic properties that govern their poroelastic behavior are modeled by an Eshelby-Mori-Tanka approach (EMTA). EMTA can account for up to 15 mineral phases. The permeability of fault damage zones affected by crack density and orientations is also predicted by an EMTA formulation. A STOMP-CO 2 grid that exactly maps the ABAQUS® finite element model is built for coupled hydro-mechanical analyses. Simulations of the reservoir assuming three different crack pattern situations (including crack volume fraction and orientation) for the fault damage zones are performed to predict the potential leakage of CO 2 due to cracks that enhance the permeability of the fault damage zones. Here, the results illustrate the important effect of the crack orientation on fault permeability that can lead to substantial leakage along the fault attained by the expansion of the CO 2 plume. Potential hydraulic fracture and the tendency for the faults to slip are also examined and discussed in terms of stress distributions and geomechanical properties.« less

Three-dimensional analysis of a faulted CO 2 reservoir using an Eshelby-Mori-Tanaka approach to rock elastic properties and fault permeability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Ba Nghiep; Hou, Zhangshuan; Last, George V.

This work develops a three-dimensional multiscale model to analyze a complex CO 2 faulted reservoir that includes some key geological features of the San Andreas and nearby faults southwest of the Kimberlina site. The model uses the STOMP-CO 2 code for flow modeling that is coupled to the ABAQUS® finite element package for geomechanical analysis. A 3D ABAQUS® finite element model is developed that contains a large number of 3D solid elements with two nearly parallel faults whose damage zones and cores are discretized using the same continuum elements. Five zones with different mineral compositions are considered: shale, sandstone, faultmore » damaged sandstone, fault damaged shale, and fault core. Rocks’ elastic properties that govern their poroelastic behavior are modeled by an Eshelby-Mori-Tanka approach (EMTA). EMTA can account for up to 15 mineral phases. The permeability of fault damage zones affected by crack density and orientations is also predicted by an EMTA formulation. A STOMP-CO 2 grid that exactly maps the ABAQUS® finite element model is built for coupled hydro-mechanical analyses. Simulations of the reservoir assuming three different crack pattern situations (including crack volume fraction and orientation) for the fault damage zones are performed to predict the potential leakage of CO 2 due to cracks that enhance the permeability of the fault damage zones. Here, the results illustrate the important effect of the crack orientation on fault permeability that can lead to substantial leakage along the fault attained by the expansion of the CO 2 plume. Potential hydraulic fracture and the tendency for the faults to slip are also examined and discussed in terms of stress distributions and geomechanical properties.« less

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Experimental postseismic recovery of fractured rocks assisted by calcite sealing

NASA Astrophysics Data System (ADS)

Aben, F. M.; Doan, M.-L.; Gratier, J.-P.; Renard, F.

2017-07-01

Postseismic recovery within fault damage zones involves slow healing of coseismic fractures leading to permeability reduction and strength increase with time. To better understand this process, experiments were performed by long-term fluid percolation with calcite precipitation through predamaged quartz-monzonite samples subjected to upper crustal conditions of stress and temperature. This resulted in a P wave velocity recovery of 50% of its initial drop after 64 days. In contrast, the permeability remained more or less constant for the duration of the experiment. Microstructures, fluid chemistry, and X-ray microtomography demonstrate that incipient calcite sealing and asperity dissolution are responsible for the P wave velocity recovery. The permeability is unaffected because calcite precipitates outside of the main flow channels. The highly nonparallel evolution of strength recovery and permeability suggests that fluid conduits within fault damage zones can remain open fluid conduits after an earthquake for much longer durations than suggested by the seismic monitoring of fault healing.

Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-19F-NMR.

PubMed

Dickinson, Elizabeth; Arnold, John R P; Fisher, Julie

2017-02-01

The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using 19 F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.

The effect of abnormal hemoglobins on the membrane regulation of cell hydration.

PubMed

Clark, M R; Shohet, S B

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.

Microvascular Permeability of Skeletal Muscle After Eccentric Contraction-Induced Muscle Injury: In Vivo Imaging Using Two-Photon Laser Scanning Microscopy.

PubMed

Hotta, Kazuki; Behnke, Bradley Jon; Masamoto, Kazuto; Shimotsu, Rie; Onodera, Naoya; Yamaguchi, Akihiko; Poole, David C; Kano, Yutaka

2018-05-03

Via modulation of endothelial integrity and vascular permeability in response to damage skeletal muscle microvessels play a crucial permissive role in tissue leukocyte invasion. However, direct visual evidence of altered microvascular permeability of skeletal muscle has not been technically feasible impairing mechanistic understanding of these responses. Two-photon laser scanning microscopy (TPLSM) allows three-dimensional in vivo imaging of skeletal muscle microcirculation. We hypothesized that the regulation of microvessels permeability in vivo is temporally related to acute inflammatory and regenerative processes following muscle injury. To test our hypothesis, tibialis anterior muscle of anesthetized male Wistar rats were subjected to eccentric contractions (ECC) via electrical stimulation. The skeletal muscle microcirculation was imaged by an intravenously infused fluorescent dye (rhodamine b isothiocyanate dextran) to assess microvascular permeability via TPLSM 1, 3 and 7 days after ECC. Immunohistochemistry on muscle sections was performed to determine the proportion of VEGF-A positive fibers in the damaged muscle. Compared with control rats, the volumetrically-determined interstitial leakage of fluorescent dye (5.1 {plus minus} 1.4, 5.3 {plus minus} 1.2 vs. 0.51 {plus minus} 0.14 μm 3 x 10 6 , P < 0.05 respectively days 1 and 3 vs. control) and percentage of VEGF-A positive fibers in the damaged muscle (10 {plus minus} 0.4, 22 {plus minus} 1.1 vs. 0%; days 1 and 3 vs. control) were significantly higher on days 1 and 3 after ECC. The interstitial leakage volume returned to control by day 7. These results suggest that microvascular hyperpermeability assessed by in vivo TPLSM imaging is associated with ECC-induced muscle damage and increased VEGF expression.

Simulations of Brady's-Type Fault Undergoing CO2 Push-Pull: Pressure-Transient and Sensitivity Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jung, Yoojin; Doughty, Christine

Input and output files used for fault characterization through numerical simulation using iTOUGH2. The synthetic data for the push period are generated by running a forward simulation (input parameters are provided in iTOUGH2 Brady GF6 Input Parameters.txt [InvExt6i.txt]). In general, the permeability of the fault gouge, damage zone, and matrix are assumed to be unknown. The input and output files are for the inversion scenario where only pressure transients are available at the monitoring well located 200 m above the injection well and only the fault gouge permeability is estimated. The input files are named InvExt6i, INPUT.tpl, FOFT.ins, CO2TAB, andmore » the output files are InvExt6i.out, pest.fof, and pest.sav (names below are display names). The table graphic in the data files below summarizes the inversion results, and indicates the fault gouge permeability can be estimated even if imperfect guesses are used for matrix and damage zone permeabilities, and permeability anisotropy is not taken into account.« less

Change in permeability of the plasma membrane of blood cells in irradiated animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shevchenko, A.S.; Kobyalko, V.O.; Lazarev, N.M.

1994-11-01

The Chernobyl nuclear disaster showed the exposure of the thyroid gland to radioactive iodine is an important factor of radiation damage to animals. Examination of domestic animals showed a marked inhibition of thyroid hormone secretion and changes in red cell membrane permeability for calcium in the absence of marked hematological shifts. At the same time the disturbed thyroid statis is associated with changes in some structural and functional parameters of blood cells. This research on calves shows that radiation damage to the thyroid produces a modifying effect on blood cell membrane permeability for calcium during both the acute and latemore » periods following exposure to 131I. 15 refs., 2 figs., 1 tab.« less

Soil quality as a factor of the distribution of damages at the meizoseismal area of the Kozani-Grevena 1995 earthquake, in Greece ( Ms = 6.6)

NASA Astrophysics Data System (ADS)

Christaras, B.; Dimitriou, An; Lemoni, Hel

The physical and mechanical properties of the soil formations were related to the damages observed in Kozani and Grevena area, in Northern Greece, after the earth-quake of 13th May 1995 ( Ms = 6.6). Properties such as grain size distribution, plasticity, shear strength, compression index, permeability and ultrasonic velocity were measured in order to classify the suitability of the soil formations, for urban planning, and correlate their mechanical behaviour with the damages observed in the construction. According to our observations, a great number of recent buildings were damaged also in areas far away from the seismotectonic zones, where silty and clayey soils dominate, presenting very low permeability, low ultrasonic velocity together with high plasticity and compressibility.

The effect of offset on fracture permeability of rocks from the Southern Andes Volcanic Zone, Chile

NASA Astrophysics Data System (ADS)

Pérez-Flores, P.; Wang, G.; Mitchell, T. M.; Meredith, P. G.; Nara, Y.; Sarkar, V.; Cembrano, J.

2017-11-01

The Southern Andes Volcanic Zone (SVZ) represents one of the largest undeveloped geothermal provinces in the world. Development of the geothermal potential requires a detailed understanding of fluid transport properties of its main lithologies. The permeability of SVZ rocks is altered by the presence of fracture damage zones produced by the Liquiñe-Ofqui Fault System (LOFS) and the Andean Transverse Faults (ATF). We have therefore measured the permeability of four representative lithologies from the volcanic basement in this area: crystalline tuff, andesitic dike, altered andesite and granodiorite. For comparative purposes, we have also measured the permeability of samples of Seljadalur basalt, an Icelandic rock with widely studied and reported hydraulic properties. Specifically, we present the results of a systematic study of the effect of fractures and fracture offsets on permeability as a function of increasing effective pressure. Baseline measurements on intact samples of SVZ rocks show that the granodiorite has a permeability (10-18 m2), two orders of magnitude higher than that of the volcanic rocks (10-20 m2). The presence of throughgoing mated macro-fractures increases permeability by between four and six orders of magnitude, with the highest permeability recorded for the crystalline tuff. Increasing fracture offset to produce unmated fractures results in large increases in permeability up to some characteristic value of offset, beyond which permeability changes only marginally. The increase in permeability with offset appears to depend on fracture roughness and aperture, and these are different for each lithology. Overall, fractured SVZ rocks with finite offsets record permeability values consistent with those commonly found in geothermal reservoirs (>10-16 m2), which potentially allow convective/advective flow to develop. Hence, our results demonstrate that the fracture damage zones developed within the SVZ produce permeable regions, especially within the transtensional NE-striking fault zones, that have major importance for geothermal energy resource potential.

Quantifying progression and regression of thrombotic risk in experimental atherosclerosis

PubMed Central

Palekar, Rohun U.; Jallouk, Andrew P.; Goette, Matthew J.; Chen, Junjie; Myerson, Jacob W.; Allen, John S.; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Pham, Christine T. N.; Wickline, Samuel A.; Pan, Hua

2015-01-01

Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200–300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [19F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy.—Palekar, R. U., Jallouk, A. P., Goette, M. J., Chen, J., Myerson, J. W., Allen, J. S., Akk, A., Yang, L., Tu, Y., Miller, M. J., Pham, C. T. N., Wickline, S. A., Pan, H. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. PMID:25857553

When it is too hot for photosynthesis: heat-induced instability of photosynthesis in relation to respiratory burst, cell permeability changes and H₂O₂ formation.

PubMed

Hüve, Katja; Bichele, Irina; Rasulov, Bahtijor; Niinemets, Ulo

2011-01-01

Photosynthesis rate (A(n)) becomes unstable above a threshold temperature, and the recovery upon return to low temperature varies because of reasons not fully understood. We investigated responses of A(n), dark respiration and chlorophyll fluorescence to supraoptimal temperatures of varying duration and kinetics in Phaseolus vulgaris asking whether the instability of photosynthesis under severe heat stress is associated with cellular damage. Cellular damage was assessed by Evans blue penetration (enhanced membrane permeability) and by H₂O₂ generation [3,3'-diaminobenzidine 4HCl (DAB)-staining]. Critical temperature for dark fluorescence (F(0) ) rise (T(F)) was at 46-48 °C, and a burst of respiration was observed near T(F). However, A(n) was strongly inhibited already before T(F) was reached. Membrane permeability increased with temperature according to a switch-type response, with enhanced permeability observed above 48 °C. Experiments with varying heat pulse lengths and intensities underscored the threshold-type loss of photosynthetic function, and indicated that the degree of photosynthetic deterioration and cellular damage depended on accumulated heat-dose. Beyond the 'point of no return', propagation of cellular damage and reduction of photosynthesis continued upon transfer to lower temperatures and photosynthetic recovery was slow or absent. We conclude that instability of photosynthesis under severe heat stress is associated with time-dependent propagation of cellular lesions. © 2010 Blackwell Publishing Ltd.

Control of the permeability of fractures in geothermal rocks

NASA Astrophysics Data System (ADS)

Faoro, Igor

This thesis comprises three journal articles that will be submitted for publication (Journal of Geophysical Research-Solid Earth). Their respective titles are: "Undrained through Drained Evolution of Permeability in Dual Permeability Media" by Igor Faoro, Derek Elsworth and Chris Marone, "Evolution of Stiffness and Permeability in Fractures Subject to Thermally-and Mechanically-Activated Dissolution" by Igor Faoro, Derek Elsworth Chris Marone; "Linking permeability and mechanical damage for basalt from Mt. Etna volcano (Italy)" by Igor Faoro, Sergio Vinciguerra, Chris Marone and Derek Elsworth. Undrained through Drained Evolution of Permeability in Dual Permeability Media: temporary permeability changes of fractured aquifers subject to earthquakes have been observed and recorded worldwide, but their comprehension still remains a complex issue. In this study we report on flow-through fracture experiments on cracked westerly cores that reproduce, at laboratory scale, those (steps like) permeability changes that have been recorded when earthquakes occur. In particular our experiments show that under specific test boundary conditions, rapid increments of pore pressure induce transient variations of flow rate of the fracture whose peak magnitudes decrease as the variations of the effective stresses increase. We identify that the observed hydraulic behavior of the fracture is due to two principal mechanisms of origin; respectively mechanical (shortening of core) and poro-elastic (radial diffusion of the pore fluid into the matrix of the sample) whose interaction cause respectively an instantaneous opening and then a progressive closure of the fracture. Evolution of Stiffness and Permeability in Fractures Subject to Thermally-and Mechanically-Activated Dissolution: we report the results of radial flow-through experiments conducted on heated samples of Westerly granite. These experiments are performed to examine the influence of thermally and mechanically activated dissolution on the mechanical (stiffness) and transport (stress-permeability) characteristics of fractures. The sample is thermally stressed to 80 °C and measurements of the constrained axial stress acting on the sample and of the flow rate of the fracture are recorded with time. Net efflux of dissolved mineral mass is also measured periodically to provide a record of rates of net mass removal. During the experiment the fracture permeability shows high sensitivity to the changing conditions of stress and temperature but no significant permanent variation of permeability have been recorded once the thermal cycle ends. Linking permeability and mechanical damage for basalt from Mt. Etna volcano (Italy): volcanic edifices, such as Mt. Etna volcano (Italy), are affected from repeated episodes of pressurization due to magma emplacement from deep reservoirs to shallow depths. This mechanism pressurizes the large aquifers within the edifice and increases the level of crack damage within the rocks of the edifice over extended periods of times. In order to improve our understanding of the complex coupling between circulating fluids and the development of crack damage we performed flow-through tests using cylindrical cores of Etna Basalt (Etna, Italy) cyclically loaded either by constant increments of the principal stress: sigma1 (deviatoric condition), or by increments of the effective confining pressure: sigma1 = sigma 2 = sigma3 (isostatic conditions). Under hydrostatic stresses, the permeability values of the intact sample decrease linearly with the increments of pressure and range between 5.2*10-17 m2 and 1.5*10-17m2. At deviatoric stresses (up to 60 MPa) the permeability from the initial value of 5*10-17 m2 slightly decays to the minimum value of 2*10 -17 m2 observed when the axial deviatoric stresses range between 40 MPa and 60 MPa. For higher deviatoric stresses, increases to 10-16 m2 are then observed up to the peak stress at 92 MPa. After failure the permeability persisted steady at the value of 8*10-16 m2 for the whole duration of the test, independently from the applied stress. We interpreted the decrease observed as due to the progressive closure of the voids space, as the axial load is incremented.

Mechanisms of ultraviolet disinfection and chlorination of Escherichia coli: Culturability, membrane permeability, metabolism, and genetic damage.

PubMed

Xu, Limei; Zhang, Chongmiao; Xu, Pengcheng; Wang, Xiaochang C

2018-03-01

Traditional culture methods may underestimate the tolerance of microorganisms to disinfectants because of the existence of viable but nonculturable or sublethally injured cells after disinfection. The selection of a strict method is crucial for the evaluation of disinfection performance. The actions of 2 typical disinfectants - ultraviolet (UV) and chlorine - on the fecal indicator Escherichia coli were investigated by the detection of culturability, membrane permeability, metabolic activity, deoxyribonucleic acid (DNA), and messenger ribonucleic acid (mRNA). During UV disinfection, the irreversible damages in the cell membrane and cellular adenosine triphosphate (ATP) were negligible at low UV doses (<80mJ/cm 2 ). However, membrane permeability was damaged at low doses of chlorine (<5mg/L), leading to leakage of cellular ATP. Our study showed that a slight lesion in DNA was detected even at high doses of UV (400mJ/cm 2 ) and chlorine (>5mg/L) treatments. The decay of mRNA was more rapid than that of DNA. The degradation level of mRNA depended on the choice of target genes. After exposure to 50mJ/cm 2 UV dose or 5mg/L chlorine for 30min, the DNA damage repair function (RecA mRNA) was inhibited. The mRNA involved in the DNA damage repair function can be a potential indicator of bacterial viability. Copyright © 2017. Published by Elsevier B.V.

Karaya gum electrocardiographic electrodes for preterm infants.

PubMed Central

Cartlidge, P H; Rutter, N

1987-01-01

Changes in transepidermal water loss were used to measure skin damage caused by removal of electrocardiograph electrodes in 20 preterm infants. Electrodes secured by conventional adhesive damaged the skin, leading to a potentially dangerous increase in skin permeability. In contrast, those secured by karaya gum caused no skin damage. PMID:3435167

Fault reactivation by fluid injection considering permeability evolution in fault-bordering damage zones

NASA Astrophysics Data System (ADS)

Yang, Z.; Yehya, A.; Rice, J. R.; Yin, J.

2017-12-01

Earthquakes can be induced by human activity involving fluid injection, e.g., as wastewater disposal from hydrocarbon production. The occurrence of such events is thought to be, mainly, due to the increase in pore pressure, which reduces the effective normal stress and hence the strength of a nearby fault. Change in subsurface stress around suitably oriented faults at near-critical stress states may also contribute. We focus on improving the modeling and prediction of the hydro-mechanical response due to fluid injection, considering the full poroelastic effects and not solely changes in pore pressure in a rigid host. Thus we address the changes in porosity and permeability of the medium due to the changes in the local volumetric strains. Our results also focus on including effects of the fault architecture (low permeability fault core and higher permeability bordering damage zones) on the pressure diffusion and the fault poroelastic response. Field studies of faults have provided a generally common description for the size of their bordering damage zones and how they evolve along their direction of propagation. Empirical laws, from a large number of such observations, describe their fracture density, width, permeability, etc. We use those laws and related data to construct our study cases. We show that the existence of high permeability damage zones facilitates pore-pressure diffusion and, in some cases, results in a sharp increase in pore-pressure at levels much deeper than the injection wells, because these regions act as conduits for fluid pressure changes. This eventually results in higher seismicity rates. By better understanding the mechanisms of nucleation of injection-induced seismicity, and better predicting the hydro-mechanical response of faults, we can assess methodologies and injection strategies to avoid risks of high magnitude seismic events. Microseismic events occurring after the start of injection are very important indications of when injection should be stopped and how to avoid major events. Our work contributes to the assessment or mitigation of seismic hazard and risk, and our long-term target question is: How to not make an earthquake?

[Effect of damage integrity rat brain synaptic membranes on the functional activity GABA(A)-receptor/Cl(-)-ionophore complex in the CNC].

PubMed

Rebrov, I G; Kalinina, M V

2013-01-01

Functional activity of the CGABA(A)-receptor/Cl(-) ionophore complex was investigated the muscimol-stimulated entry of the radioactive isotope 36Cl(-) in synaptoneurosomes in changing the structure and permeability of neuronal membranes. Integrity of the membranes was damaged by removal of Ca(+2) and Mg(+2) from the incubation medium and by the method of freezing-thawing synaptoneurosomes. In both cases, an increase in basal 36Cl(-) entry into synaptoneurosomes, indicating increased nonspecific permeability of neuronal membranes, and decreased activity the CABA(A)-receptor/Cl(-) ionophore complex. The conclusion about the relationship of processes damage neuronal membranes and reducing the inhibitory processes in the epileptic focus.

Resin Film Infusion (RFI) Process Modeling for Large Transport Aircraft Wing Structures

NASA Technical Reports Server (NTRS)

Knott, Tamara W.; Loos, Alfred C.

2000-01-01

Resin film infusion (RFI) is a cost-effective method for fabricating stiffened aircraft wing structures. The RFI process lends itself to the use of near net shape textile preforms manufactured through a variety of automated textile processes such as knitting and braiding. Often, these advanced fiber architecture preforms have through-the-thickness stitching for improved damage tolerance and delamination resistance. The challenge presently facing RFI is to refine the process to ensure complete infiltration and cure of a geometrically complex shape preform with the high fiber volume fraction needed for structural applications. An accurate measurement of preform permeability is critical for successful modeling of the RFI resin infiltration process. Small changes in the permeability can result in very different infiltration behavior and times. Therefore, it is important to accurately measure the permeabilities of the textile preforms used in the RFI process. The objective of this investigation was to develop test methods that can be used to measure the compaction behavior and permeabilities of high fiber volume fraction, advanced fiber architecture textile preforms. These preforms are often highly compacted due to through-the-thickness stitching used to improve damage tolerance. Test fixtures were designed and fabricated and used to measure both transverse and in-plane permeabilities. The fixtures were used to measure the permeabilities of multiaxial warp knit and triaxial braided preforms at fiber volume fractions from 55% to 65%. In addition, the effects of stitching characteristics, thickness, and batch variability on permeability and compaction behavior were investigated.

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

46 CFR 174.207 - Damaged stability criteria.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Permeability of spaces. The permeability of a floodable space must be as specified by Table 174.207(b) of this...) Equipped with arrangements, such as stop check-valves, to prevent progressive flooding of the spaces with... permit progressive flooding of the spaces with which they connect. (d) Buoyancy of superstructure. For...

Low resistivity and permeability in actively deforming shear zones on the San Andreas Fault at SAFOD

USGS Publications Warehouse

Morrow, Carolyn A.; Lockner, David A.; Hickman, Stephen H.

2015-01-01

The San Andreas Fault Observatory at Depth (SAFOD) scientific drillhole near Parkfield, California crosses the San Andreas Fault at a depth of 2.7 km. Downhole measurements and analysis of core retrieved from Phase 3 drilling reveal two narrow, actively deforming zones of smectite-clay gouge within a roughly 200 m-wide fault damage zone of sandstones, siltstones and mudstones. Here we report electrical resistivity and permeability measurements on core samples from all of these structural units at effective confining pressures up to 120 MPa. Electrical resistivity (~10 ohm-m) and permeability (10-21 to 10-22 m2) in the actively deforming zones were one to two orders of magnitude lower than the surrounding damage zone material, consistent with broader-scale observations from the downhole resistivity and seismic velocity logs. The higher porosity of the clay gouge, 2 to 8 times greater than that in the damage zone rocks, along with surface conduction were the principal factors contributing to the observed low resistivities. The high percentage of fine-grained clay in the deforming zones also greatly reduced permeability to values low enough to create a barrier to fluid flow across the fault. Together, resistivity and permeability data can be used to assess the hydrogeologic characteristics of the fault, key to understanding fault structure and strength. The low resistivities and strength measurements of the SAFOD core are consistent with observations of low resistivity clays that are often found in the principal slip zones of other active faults making resistivity logs a valuable tool for identifying these zones.

Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.

PubMed

Proia, Patrizia; Schiera, Gabriella; Salemi, Giuseppe; Ragonese, Paolo; Savettieri, Giovanni; Di Liegro, Italia

2009-12-01

An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the permeability of the BBB model, as indicated by the decrease of the transendothelial electrical resistance (TEER). Moreover, as shown by both immunofluorescence and Western blot analyses, BBB breaking is accompanied by a decrease of the synthesis as well as the peripheral localization of occludin, a structural protein of the tight junctions that are responsible for BBB properties.

Chloride Permeability of Damaged High-Performance Fiber-Reinforced Cement Composite by Repeated Compressive Loads.

PubMed

Lee, Byung Jae; Hyun, Jung Hwan; Kim, Yun Yong; Shin, Kyung Joon

2014-08-11

The development of cracking in concrete structures leads to significant permeability and to durability problems as a result. Approaches to controlling crack development and crack width in concrete structures have been widely debated. Recently, it was recognized that a high-performance fiber-reinforced cement composite (HPFRCC) provides a possible solution to this inherent problem of cracking by smearing one or several dominant cracks into many distributed microcracks under tensile loading conditions. However, the chloride permeability of HPFRCC under compressive loading conditions is not yet fully understood. Therefore, the goal of the present study is to explore the chloride diffusion characteristics of HPFRCC damaged by compressive loads. The chloride diffusivity of HPFRCC is measured after being subjected to various repeated loads. The results show that the residual axial strain, lateral strain and specific crack area of HPFRCC specimens increase with an increase in the damage induced by repeated loads. However, the chloride diffusion coefficient increases only up to 1.5-times, whereas the specific crack area increases up to 3-times with an increase in damage. Although HPFRCC shows smeared distributed cracks in tensile loads, a significant reduction in the diffusion coefficient of HPFRCC is not obtained compared to plain concrete when the cyclic compressive load is applied below 85% of the strength.

Oil permeability variations on lagoon sand beaches in the Patos-Guaíba system in Rio Grande do Sul, Brazil.

PubMed

Oliveira, Elaine Baroni; Nicolodi, João Luiz

2017-02-15

Permeability is the ability of a sediment deposit to allow fluids to pass through it. It depends on the local types of sediments. When the fluid is oil, high permeability implies greater interaction with the site and more extensive damage, which makes recovery most difficult. Knowledge of permeability oscillations is necessary to understand oil behavior and improve cleanup techniques. The goal is to determine oil permeability variations on lagoon sand beaches. Oil permeability tests were performed at the beach face, using a Modified Phillip Dunne Permeameter and parameters were sampled. Permeability of lagoon beaches is driven by grain diameter and roundness, soil compaction, and depth of the water table. Factors that enhance permeability include: sand sorting, vertical distribution of sediments and gravel percentage. High permeability on lagoon beaches is related to polymodal distribution, to the sediment package, and to the system's low mobility. Copyright © 2016 Elsevier Ltd. All rights reserved.

Permeability Evolution of Slowly Slipping Faults in Shale Reservoirs

NASA Astrophysics Data System (ADS)

Wu, Wei; Reece, Julia S.; Gensterblum, Yves; Zoback, Mark D.

2017-11-01

Slow slip on preexisting faults during hydraulic fracturing is a process that significantly influences shale gas production in extremely low permeability "shale" (unconventional) reservoirs. We experimentally examined the impacts of mineralogy, surface roughness, and effective stress on permeability evolution of slowly slipping faults in Eagle Ford shale samples. Our results show that fault permeability decreases with slip at higher effective stress but increases with slip at lower effective stress. The permeabilities of saw cut faults fully recover after cycling effective stress from 2.5 to 17.5 to 2.5 MPa and increase with slip at constant effective stress due to asperity damage and dilation associated with slip. However, the permeabilities of natural faults only partially recover after cycling effective stress returns to 2.5 MPa and decrease with slip due to produced gouge blocking fluid flow pathways. Our results suggest that slowly slipping faults have the potential to enhance reservoir stimulation in extremely low permeability reservoirs.

Numerical Investigation of the Turbulent Wind Flow Through Elevated Windbreak

NASA Astrophysics Data System (ADS)

Agarwal, Ashish; Irtaza, Hassan

2018-06-01

Analysis of airflow through elevated windbreaks is presented in this paper. Permeable nets and impermeable film increases considerable wind forces on the windbreaks which is susceptible to damage during high wind. A comprehensive numerical investigation has been carried out to analyze the effects of wind on standalone elevated windbreak clad with various permeable nets and an impermeable film. The variation of airflow behavior around and through permeable nets and airflow behavior around impermeable film were also been investigated. Computational fluid dynamics techniques using Reynolds Averaged Navier-Stokes equations has been used to predict the wind force coefficient and thus wind forces on panels supporting permeable nets and impermeable film for turbulent wind flow. Elevated windbreak panels were analyzed for seven different permeable nets having various solidity ratio, specific permeability and aerodynamic resistant coefficients. The permeable nets were modelled as porous jump media obeying Forchheimer's law and an impermeable film modelled as rigid wall.

Numerical Investigation of the Turbulent Wind Flow Through Elevated Windbreak

NASA Astrophysics Data System (ADS)

Agarwal, Ashish; Irtaza, Hassan

2018-04-01

Analysis of airflow through elevated windbreaks is presented in this paper. Permeable nets and impermeable film increases considerable wind forces on the windbreaks which is susceptible to damage during high wind. A comprehensive numerical investigation has been carried out to analyze the effects of wind on standalone elevated windbreak clad with various permeable nets and an impermeable film. The variation of airflow behavior around and through permeable nets and airflow behavior around impermeable film were also been investigated. Computational fluid dynamics techniques using Reynolds Averaged Navier-Stokes equations has been used to predict the wind force coefficient and thus wind forces on panels supporting permeable nets and impermeable film for turbulent wind flow. Elevated windbreak panels were analyzed for seven different permeable nets having various solidity ratio, specific permeability and aerodynamic resistant coefficients. The permeable nets were modelled as porous jump media obeying Forchheimer's law and an impermeable film modelled as rigid wall.

Acute carbon tetrachloride induced lysosomal membrane damage and the membrane protecting effect of a new dihydroquinoline-type antioxidant.

PubMed

Toncsev, H; Pollák, Z; Kiss, A; Sréter, L; Fehér, J

1982-01-01

The authors examined the damage of lysosomal membrane caused by acute CCl4 intoxication by in vitro methods. They measured the acid phosphatase as well as beta-glucuronidase enzyme levels and determined the rate of release of these two enzymes. The in vivo changes in enzyme activity were extrapolated from the in vitro results. The CCl4 causes a significant increase in the permeability and rigidity of the lysosomal membrane. By oral and/or intraperitoneal administration of MTDQ the state of permeability can be improved or even corrected. On the basis of their results, the authors conclude that the lysosomal damage caused by CCl4 is mediated by peroxidation of lipids and the lysosomal membrane can be stabilised by MTDQ.

Geometry of the Nojima fault at Nojima-Hirabayashi, Japan - II. Microstructures and their implications for permeability and strength

USGS Publications Warehouse

Moore, Diane E.; Lockner, D.A.; Ito, H.; Ikeda, R.; Tanaka, H.; Omura, K.

2009-01-01

Samples of damage-zone granodiorite and fault core from two drillholes into the active, strike-slip Nojima fault zone display microstructures and alteration features that explain their measured present-day strengths and permeabilities and provide insight on the evolution of these properties in the fault zone. The least deformed damage-zone rocks contain two sets of nearly perpendicular (60-90?? angles), roughly vertical fractures that are concentrated in quartz-rich areas, with one set typically dominating over the other. With increasing intensity of deformation, which corresponds generally to increasing proximity to the core, zones of heavily fragmented rock, termed microbreccia zones, develop between prominent fractures of both sets. Granodiorite adjoining intersecting microbreccia zones in the active fault strands has been repeatedly fractured and locally brecciated, accompanied by the generation of millimeter-scale voids that are partly filled with secondary minerals. Minor shear bands overprint some of the heavily deformed areas, and small-scale shear zones form from the pairing of closely spaced shear bands. Strength and permeability measurements were made on core collected from the fault within a year after a major (Kobe) earthquake. Measured strengths of the samples decrease regularly with increasing fracturing and fragmentation, such that the gouge of the fault core and completely brecciated samples from the damage zone are the weakest. Permeability increases with increasing disruption, generally reaching a peak in heavily fractured but still more or less cohesive rock at the scale of the laboratory samples. Complete loss of cohesion, as in the gouge or the interiors of large microbreccia zones, is accompanied by a reduction of permeability by 1-2 orders of magnitude below the peak values. The core samples show abundant evidence of hydrothermal alteration and mineral precipitation. Permeability is thus expected to decrease and strength to increase somewhat in active fault strands between earthquakes, as mineral deposits progressively seal fractures and fill pore spaces. ?? Birkh??user Verlag, Basel 2009.

Acute high-intensity interval running increases markers of gastrointestinal damage and permeability but not gastrointestinal symptoms.

PubMed

Pugh, Jamie N; Impey, Samuel G; Doran, Dominic A; Fleming, Simon C; Morton, James P; Close, Graeme L

2017-09-01

The purpose of this study was to investigate the effects of high-intensity interval running on markers of gastrointestinal (GI) damage and permeability alongside subjective symptoms of GI discomfort. Eleven male runners completed an acute bout of high-intensity interval training (HIIT) (eighteen 400-m runs at 120% maximal oxygen uptake) where markers of GI permeability, intestinal damage, and GI discomfort symptoms were assessed and compared with resting conditions. Compared with rest, HIIT significantly increased serum lactulose/rhamnose ratio (0.051 ± 0.016 vs. 0.031 ± 0.021, p = 0.0047; 95% confidence interval (CI) = 0.006 to 0.036) and sucrose concentrations (0.388 ± 0.217 vs. 0.137 ± 0.148 mg·L -1 ; p < 0.001; 95% CI = 0.152 to 0.350). In contrast, urinary lactulose/rhamnose (0.032 ± 0.005 vs. 0.030 ± 0.005; p = 0.3; 95% CI = -0.012 to 0.009) or sucrose concentrations (0.169% ± 0.168% vs. 0.123% ± 0.120%; p = 0.54; 95% CI = -0.199 to 0.108) did not differ between HIIT and resting conditions. Plasma intestinal-fatty acid binding protein (I-FABP) was significantly increased (p < 0.001) during and in the recovery period from HIIT whereas no changes were observed during rest. Mild symptoms of GI discomfort were reported immediately and at 24 h post-HIIT, although these symptoms did not correlate to GI permeability or I-FABP. In conclusion, acute HIIT increased GI permeability and intestinal I-FABP release, although these do not correlate with symptoms of GI discomfort. Furthermore, by using serum sampling, we provide data showing that it is possible to detect changes in intestinal permeability that is not observed using urinary sampling over a shorter time-period.

Fluid Overpressure and Earthquakes Triggering in the Natural Laboratory of the Northern Apennines: Integration of Field and Laboratory Data

NASA Astrophysics Data System (ADS)

de Paola, N.; Collettini, C.; Faulkner, D.

2007-12-01

The integration of seismic reflection profiles with well-located earthquakes show that the mainshocks of the 1997-1998 Colfiorito seismic sequence (Central Italy) nucleated at a depth of ~6 km within the Triassic Evaporites (TE, anhydrites and dolostones), where CO2 at near lithostatic pressure has been encountered in two deep boreholes (4 km). In order to investigate the deformation processes operating at depth in the source region of the Colfiorito earthquakes we have characterized: 1) fault zone structure by studying exhumed outcrops of the temperature, 100 MPa confining pressure (Pc), and range of pore fluid pressures (Pf). Permeability and porosity development was continuously measured throughout the deformation experiments. The architecture of large fault zones within the TE is given by a distinct fault core, where most of the shear strain has been accommodated, surrounded by a geometrically complex and heterogeneous damage zone. Brittle deformation within the fault core is extremely localized along principal slip surfaces associated with dolomite rich cataclasite seams, running parallel to the fault zone. The damage zone is characterized by adjacent zones of heavily fractured rocks (dolostones) and foliated rocks displaying little fracturing (anhydrites). Static permeability measurements on anhydrite samples show increasing values of permeability for decreasing values of Pe, (k = 10E-20 - 10E-22 m2). During single cycle loading tests the permeability values immediately prior to failure are about three orders of magnitude higher than the initial values. The field data suggests that during the seismic cycle, the permeability of the dolostones, within the damage zone, is likely to be high and controlled by mesoscale fracture patterns. Conversely, the permeability of the anhydrites, due to the absence of mesoscale fracture patterns within Ca-sulphates layers, may be potentially as low as the values measured in the lab experiments (k = 10E-17 - 10E-22 m2). This suggests that fluid overpressure can be maintained in this lithology, within the damage zone, as far as the co-seismic period. Our observations and results can be applied to explain the seismicity of the Northern Apennines and other regions where fluids overpressures play a key role in triggering fault instability and earthquakes.

Fluid Overpressure and Earthquakes Triggering in the Natural Laboratory of the Northern Apennines: Integration of Field and Laboratory Data

NASA Astrophysics Data System (ADS)

de Paola, N.; Collettini, C.; Faulkner, D.

2004-12-01

The integration of seismic reflection profiles with well-located earthquakes show that the mainshocks of the 1997-1998 Colfiorito seismic sequence (Central Italy) nucleated at a depth of ~6 km within the Triassic Evaporites (TE, anhydrites and dolostones), where CO2 at near lithostatic pressure has been encountered in two deep boreholes (4 km). In order to investigate the deformation processes operating at depth in the source region of the Colfiorito earthquakes we have characterized: 1) fault zone structure by studying exhumed outcrops of the temperature, 100 MPa confining pressure (Pc), and range of pore fluid pressures (Pf). Permeability and porosity development was continuously measured throughout the deformation experiments. The architecture of large fault zones within the TE is given by a distinct fault core, where most of the shear strain has been accommodated, surrounded by a geometrically complex and heterogeneous damage zone. Brittle deformation within the fault core is extremely localized along principal slip surfaces associated with dolomite rich cataclasite seams, running parallel to the fault zone. The damage zone is characterized by adjacent zones of heavily fractured rocks (dolostones) and foliated rocks displaying little fracturing (anhydrites). Static permeability measurements on anhydrite samples show increasing values of permeability for decreasing values of Pe, (k = 10E-20 - 10E-22 m2). During single cycle loading tests the permeability values immediately prior to failure are about three orders of magnitude higher than the initial values. The field data suggests that during the seismic cycle, the permeability of the dolostones, within the damage zone, is likely to be high and controlled by mesoscale fracture patterns. Conversely, the permeability of the anhydrites, due to the absence of mesoscale fracture patterns within Ca-sulphates layers, may be potentially as low as the values measured in the lab experiments (k = 10E-17 - 10E-22 m2). This suggests that fluid overpressure can be maintained in this lithology, within the damage zone, as far as the co-seismic period. Our observations and results can be applied to explain the seismicity of the Northern Apennines and other regions where fluids overpressures play a key role in triggering fault instability and earthquakes.

Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat.

PubMed

Somasundaram, S; Sigthorsson, G; Simpson, R J; Watts, J; Jacob, M; Tavares, I A; Rafi, S; Roseth, A; Foster, R; Price, A B; Wrigglesworth, J M; Bjarnason, I

2000-05-01

The pathogenesis of NSAID-induced gastrointestinal damage is believed to involve a nonprostaglandin dependent effect as well as prostaglandin dependent effects. One suggestion is that the nonprostaglandin mechanism involves uncoupling of mitochondrial oxidative phosphorylation. To assess the role of uncoupling of mitochondrial oxidative phosphorylation in the pathogenesis of small intestinal damage in the rat. We compared key pathophysiologic events in the small bowel following (i) dinitrophenol, an uncoupling agent (ii) parenteral aspirin, to inhibit cyclooxygenase without causing a 'topical' effect and (iii) the two together, using (iv) indomethacin as a positive control. Dinitrophenol altered intestinal mitochondrial morphology, increased intestinal permeability and caused inflammation without affecting gastric permeability or intestinal prostanoid levels. Parenteral aspirin decreased mucosal prostanoids without affecting intestinal mitochondria in vivo, gastric or intestinal permeability. Aspirin caused no inflammation or ulcers. When dinitrophenol and aspirin were given together the changes in intestinal mitochondrial morphology, permeability, inflammation and prostanoid levels and the macro- and microscopic appearances of intestinal ulcers were similar to indomethacin. These studies allow dissociation of the contribution and consequences of uncoupling of mitochondrial oxidative phosphorylation and cyclooxygenase inhibition in the pathophysiology of NSAID enteropathy. While uncoupling of enterocyte mitochondrial oxidative phosphorylation leads to increased intestinal permeability and low grade inflammation, concurrent decreases in mucosal prostanoids appear to be important in the development of ulcers.

Permeability of Granite Including Macro-Fracture Naturally Filled with Fine-Grained Minerals

NASA Astrophysics Data System (ADS)

Nara, Yoshitaka; Kato, Masaji; Niri, Ryuhei; Kohno, Masanori; Sato, Toshinori; Fukuda, Daisuke; Sato, Tsutomu; Takahashi, Manabu

2018-03-01

Information on the permeability of rock is essential for various geoengineering projects, such as geological disposal of radioactive wastes, hydrocarbon extraction, and natural hazard risk mitigation. It is especially important to investigate how fractures and pores influence the physical and transport properties of rock. Infiltration of groundwater through the damage zone fills fractures in granite with fine-grained minerals. However, the permeability of rock possessing a fracture naturally filled with fine-grained mineral grains has yet to be investigated. In this study, the permeabilities of granite samples, including a macro-fracture filled with clay and a mineral vein, are investigated. The permeability of granite with a fine-grained mineral vein agrees well with that of the intact sample, whereas the permeability of granite possessing a macro-fracture filled with clay is lower than that of the macro-fractured sample. The decrease in the permeability is due to the filling of fine-grained minerals and clay in the macro-fracture. It is concluded that the permeability of granite increases due to the existence of the fractures, but decreases upon filling them with fine-grained minerals.

A novel enzyme-based acidizing system: Matrix acidizing and drilling fluid damage removal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harris, R.E.; McKay, D.M.; Moses, V.

1995-12-31

A novel acidizing process is used to increase the permeability of carbonate rock cores in the laboratory and to remove drilling fluid damage from cores and wafers. Field results show the benefits of the technology as applied both to injector and producer wells.

33 CFR Appendix B to Part 157 - Subdivision and Stability Assumptions

Code of Federal Regulations, 2012 CFR

2012-07-01

... liquids from damaged compartments. (b) The permeabilities are assumed as follows: Intended space use... space located aft is involved in the damage assumption. The machinery space is calculated as a single... between adjacent transverse bulkheads except the machinery space. (b) The extent and the character of the...

33 CFR Appendix B to Part 157 - Subdivision and Stability Assumptions

Code of Federal Regulations, 2011 CFR

2011-07-01

... liquids from damaged compartments. (b) The permeabilities are assumed as follows: Intended space use... space located aft is involved in the damage assumption. The machinery space is calculated as a single... between adjacent transverse bulkheads except the machinery space. (b) The extent and the character of the...

33 CFR Appendix B to Part 157 - Subdivision and Stability Assumptions

Code of Federal Regulations, 2014 CFR

2014-07-01

... liquids from damaged compartments. (b) The permeabilities are assumed as follows: Intended space use... space located aft is involved in the damage assumption. The machinery space is calculated as a single... between adjacent transverse bulkheads except the machinery space. (b) The extent and the character of the...

33 CFR Appendix B to Part 157 - Subdivision and Stability Assumptions

Code of Federal Regulations, 2010 CFR

2010-07-01

... liquids from damaged compartments. (b) The permeabilities are assumed as follows: Intended space use... space located aft is involved in the damage assumption. The machinery space is calculated as a single... between adjacent transverse bulkheads except the machinery space. (b) The extent and the character of the...

33 CFR Appendix B to Part 157 - Subdivision and Stability Assumptions

Code of Federal Regulations, 2013 CFR

2013-07-01

... liquids from damaged compartments. (b) The permeabilities are assumed as follows: Intended space use... space located aft is involved in the damage assumption. The machinery space is calculated as a single... between adjacent transverse bulkheads except the machinery space. (b) The extent and the character of the...

Permeability evolution of shale during spontaneous imbibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, N.; Karpyn, Z. T.; Liu, S.

Shales have small pore and throat sizes ranging from nano to micron scales, low porosity and limited permeability. The poor permeability and complex pore connectivity of shales pose technical challenges to (a) understanding flow and transport mechanisms in such systems and, (b) in predicting permeability changes under dynamic saturation conditions. This paper presents quantitative experimental evidence of the migration of water through a generic shale core plug using micro CT imaging. In addition, in-situ measurements of gas permeability were performed during counter-current spontaneous imbibition of water in nano-darcy permeability Marcellus and Haynesville core plugs. It was seen that water blocksmore » severely reduced the effective permeability of the core plugs, leading to losses of up to 99.5% of the initial permeability in experiments lasting 30 days. There was also evidence of clay swelling which further hindered gas flow. When results from this study were compared with similar counter-current gas permeability experiments reported in the literature, the initial (base) permeability of the rock was found to be a key factor in determining the time evolution of effective gas permeability during spontaneous imbibition. With time, a recovery of effective permeability was seen in the higher permeability rocks, while becoming progressively detrimental and irreversible in tighter rocks. Finally, these results suggest that matrix permeability of ultra-tight rocks is susceptible to water damage following hydraulic fracturing stimulation and, while shut-in/soaking time helps clearing-up fractures from resident fluid, its effect on the adjacent matrix permeability could be detrimental.« less

Permeability evolution of shale during spontaneous imbibition

DOE PAGES

Chakraborty, N.; Karpyn, Z. T.; Liu, S.; ...

2017-01-05

Shales have small pore and throat sizes ranging from nano to micron scales, low porosity and limited permeability. The poor permeability and complex pore connectivity of shales pose technical challenges to (a) understanding flow and transport mechanisms in such systems and, (b) in predicting permeability changes under dynamic saturation conditions. This paper presents quantitative experimental evidence of the migration of water through a generic shale core plug using micro CT imaging. In addition, in-situ measurements of gas permeability were performed during counter-current spontaneous imbibition of water in nano-darcy permeability Marcellus and Haynesville core plugs. It was seen that water blocksmore » severely reduced the effective permeability of the core plugs, leading to losses of up to 99.5% of the initial permeability in experiments lasting 30 days. There was also evidence of clay swelling which further hindered gas flow. When results from this study were compared with similar counter-current gas permeability experiments reported in the literature, the initial (base) permeability of the rock was found to be a key factor in determining the time evolution of effective gas permeability during spontaneous imbibition. With time, a recovery of effective permeability was seen in the higher permeability rocks, while becoming progressively detrimental and irreversible in tighter rocks. Finally, these results suggest that matrix permeability of ultra-tight rocks is susceptible to water damage following hydraulic fracturing stimulation and, while shut-in/soaking time helps clearing-up fractures from resident fluid, its effect on the adjacent matrix permeability could be detrimental.« less

Normal reference values for regional pulmonary peripheral airspace epithelial permeability. Influence of pneumonectomy and the smoking habit.

PubMed

Todisco, T; Dottorini, M; Rossi, F; Baldoncini, A; Palumbo, R

1989-01-01

Peripheral airspace epithelial permeability (PAEP) to diethylentriaminopentacetate (DTPA), an index of pulmonary integrity, was measured in 3 groups of subjects for different purposes: (1) to establish vertical regional reference values; (2) to determine the physiological role of acute doubling of total pulmonary blood flow; (3) to quantify the pulmonary epithelial damage in smokers and the possibility of lung protection by an agent stimulating surfactant production. This study broadens previous knowledge of PAEP. First of all, regional reference values are given for young normal nonsmoking subjects and the existence of a vertical gradient of PAEP is confirmed. Furthermore, this study shows that this gradient is independent of the vertical blood flow gradient, since an acute increase of total blood flow in pneumonectomized patients does not modify the regional distribution of PAEP. Finally, it is confirmed that the cigarette smoker's lung is more permeable than the controls and that probably a drug-stimulating surfactant production gives some protection against damage due to chronic smoking.

Sub-Lethal Dose of Shiga Toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cytoarchitecture

PubMed Central

Pinto, Alipio; Cangelosi, Adriana; Geoghegan, Patricia A.; Tironi-Farinati, Carla; Brener, Gabriela J.; Goldstein, Jorge

2016-01-01

Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic–uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however, the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood–brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test), and ultrastructural analysis (transmission electron microscope). Intravenous administration of vehicle (control group), sub-lethal dose of 0.5 and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n = 6). Blood–brain barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1 ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance. PMID:26904009

Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells.

PubMed

Hirotani, Yoshihiko; Ikeda, Kenji; Kato, Ryuji; Myotoku, Michiaki; Umeda, Takashi; Ijiri, Yoshio; Tanaka, Kazuhiko

2008-09-01

Indirect evidence suggests that lactoferrin (Lf), a major iron-binding protein in human milk, induces enterocyte growth and proliferation, depending on its concentration and affects the function and permeability of the intestinal mucosa. The bacterial endotoxin (lipopolysaccharide, LPS) is known to cause mucosal hyperpermeability in vivo. However, protective effects of Lf against LPS-mediated intestinal mucosal damage and barrier function in epithelial cells are not yet fully clarified. The aim of this study was to investigate whether Lf can reduce the cellular injury and alter epithelial hyperpermeability caused by LPS in human intestinal Caco-2 cells. When cell viability was measured by a WST-1 assay (tetrazolium salt-based assay), the protective effects against LPS-induced damage to Caco-2 cells were observed at doses of 800 and 1000 microg/ml Lf. The barrier function of Caco-2 monolayer tight junctions was assessed by measuring transepithelial electrical resistance (TEER) and permeability of FITC-labeled dextran 4000 (FD-4). The treatment of Caco-2 cells with Lf at doses of 400 and 1000 microg/ml significantly increased TEER as compared to treatment with LPS alone for 2 h (p<0.05). Further, at doses of 400 and 1000 microg/ml, Lf inhibited the enhancement of LPS-mediated permeability in Caco-2 cell monolayer. The results of this study suggest that Lf may have protective effects against LPS-mediated intestinal mucosal damage and impairment of barrier function in intestinal epithelial cells.

Acoustic Cavitation-Based Monitoring of the Reversibility and Permeability of Ultrasound-Induced Blood-Brain Barrier Opening

PubMed Central

Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.

2015-01-01

Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n = 60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 days thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: 1) the duration of the BBB opening (r2 = 0.77); 2) the permeability of the opened BBB (r2 = 0.82); 3) the likelihood of safe opening (P < 0.05, safe opening compared to cases of damage; P < 0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r2 = 0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions. PMID:26562661

Relationship between lesion formation and permeability of rat gastric mucosa to H+ and other cations.

PubMed

Bunce, K T; McCarthy, J J; Spraggs, C F; Stables, R

1982-02-01

The relationship between lesion formation and ionic permeability has been investigated in rat gastric mucosa in vivo. Changes in these parameters were measured in the mucosa treated topically with prostaglandins E2 and A2 and/or aspirin. Particular attention was paid to the net flux of H+ ions across the gastric mucosa. The effect of aspirin concentrations of 5 mM, 20 mM and '40 mM' (the latter, a suspension in a saturated solution) was investigated. Aspirin concentrations of 20 mM and '40 mM' produced a marked increase in lesion formation and increased the net mucosal to serosal flux of H+ ions. Aspirin 5 mM produced a significant increase in lesion formation but did not cause a significant change in net H+ ion flux. This result suggests that aspirin can have a direct irritant effect on the gastric mucosa and that the back diffusion of H+ ions is not a pre-requisite for the development of overt mucosal ulceration. The effect of topically applied prostaglandin E2 (PGE2) on aspirin-induced gastric mucosal damage was investigated. Concentrations of PGE2 of 10(-5) M and 10(-4) M ameliorated aspirin-induced damage, but these changes were not necessarily accompanied by a significant reduction in net H+ ion flux. Again, this result is not consistent with a direct relationship between lesion formation and mucosal permeability to H+ ions. Since PGA2 did not ameliorate aspirin-induced mucosal damage, the protective effect of PGE2 could not be attributed to its conversion to PGA2 in the acidic environment of the gastric lumen. 5 Changes in gastric mucosal potential difference (p.d.) and net fluxes of Na+ and K+ ions may occur without a concomitant change in the permeability of the gastric mucosa to acid back-diffusion. Thus, the assumption cannot be made that a change in the permeability of the gastric mucosa to one particular ion reflects a general increase in ionic permeability.

Three-dimensional characterization of microporosity and permeability in fault zones hosted in heterolithic succession

NASA Astrophysics Data System (ADS)

Riegel, H. B.; Zambrano, M.; Jablonska, D.; Emanuele, T.; Agosta, F.; Mattioni, L.; Rustichelli, A.

2017-12-01

The hydraulic properties of fault zones depend upon the individual contributions of the damage zone and the fault core. In the case of the damage zone, it is generally characterized by means of fracture analysis and modelling implementing multiple approaches, for instance the discrete fracture network model, the continuum model, and the channel network model. Conversely, the fault core is more difficult to characterize because it is normally composed of fine grain material generated by friction and wear. If the dimensions of the fault core allows it, the porosity and permeability are normally studied by means of laboratory analysis or in the other case by two dimensional microporosity analysis and in situ measurements of permeability (e.g. micro-permeameter). In this study, a combined approach consisting of fracture modeling, three-dimensional microporosity analysis, and computational fluid dynamics was applied to characterize the hydraulic properties of fault zones. The studied fault zones crosscut a well-cemented heterolithic succession (sandstone and mudstones) and may vary in terms of fault core thickness and composition, fracture properties, kinematics (normal or strike-slip), and displacement. These characteristics produce various splay and fault core behavior. The alternation of sandstone and mudstone layers is responsible for the concurrent occurrence of brittle (fractures) and ductile (clay smearing) deformation. When these alternating layers are faulted, they produce corresponding fault cores which act as conduits or barriers for fluid migration. When analyzing damage zones, accurate field and data acquisition and stochastic modeling was used to determine the hydraulic properties of the rock volume, in relation to the surrounding, undamaged host rock. In the fault cores, the three-dimensional pore network quantitative analysis based on X-ray microtomography images includes porosity, pore connectivity, and specific surface area. In addition, images were used to perform computational fluid simulation (Lattice-Boltzmann multi relaxation time method) and estimate the permeability. These results will be useful for understanding the deformation process and hydraulic properties across meter-scale damage zones.

Palaeopermeability anisotropies of a strike-slip fault damage zone: 3D Insights of quantitative fluid flow from µCT analysis.

NASA Astrophysics Data System (ADS)

Gomila, R.; Arancibia, G.; Nehler, M.; Bracke, R.; Morata, D.

2017-12-01

Fault zones and their related structural permeability are a key aspect in the migration of fluids through the continental crust. Therefore, the estimation of the hydraulic properties (palaeopermeability conditions; k) and the spatial distribution of the fracture mesh within the damage zone (DZ) are critical in the assessment of fault zones behavior for fluids. The study of the real spatial distribution of the veinlets of the fracture mesh (3D), feasible with the use of µCT analyses, is a first order factor to unravel both, the real structural permeability conditions of a fault-zone, and the validation of previous (and classical) estimations made in 2D analyses in thin-sections. This work shows the results of a fault-related fracture mesh and its 3D spatial distribution in the damage-zone of the Jorgillo Fault (JF), an ancient subvertical left-lateral strike-slip fault exposed in the Atacama Fault System in northern Chile. The JF is a ca. 20 km long NNW-striking strike-slip fault with sinistral displacement of ca. 4 km. The methodology consisted of drilling 5 mm vertically oriented plugs at several locations within the JF damage zone. Each specimen was scanned with an X-Ray µCT scanner, to assess the fracture mesh, with a voxel resolution of ca. 4.5 µm in the 3D reconstructed data. Tensor permeability modeling, using Lattice-Boltzmann Method, through the segmented microfracture mesh show GMkmin (geometric mean values) of 2.1x10-12 and 9.8x10-13 m2, and GMkmax of 6.4x10-12 and 2.1x10-12 m2. A high degree of anisotropy of the DZ permeability tensor both sides of the JF (eastern and western side, respectively) is observed, where the k values in the kmax plane are 2.4 and 1.9 times higher than the kmin direction at the time of fracture sealing. This style of anisotropy is consistent with the obtained for bedded sandstones supporting the idea that damage zones have an analogous effect - but vertically orientated - on bulk permeability (in low porosity rocks) as stratigraphic layering, where across-strike khorizontal of a fault is lower when compared with the kvertical and kfault parallel. Acknowledgements: This work is a contribution to FONDAP-CONICYT Project 15090013 and CONICYT- BMBF International Scientific Collaborative Research Program Project PCCI130025/FKZ01DN14033. R.G. Ph.D. is funded by CONICYT Scholarship 21140021.

Theoretical predicting of permeability evolution in damaged rock under compressive stress

NASA Astrophysics Data System (ADS)

Vu, M. N.; Nguyen, S. T.; To, Q. D.; Dao, N. H.

2017-05-01

This paper outlines an analytical model of crack growth induced permeability changes. A theoretical solution of effective permeability of cracked porous media is derived. The fluid flow obeys Poisseuille's law along the crack and Darcy's law in the porous matrix. This solution exhibits a percolation threshold for any type of crack distribution apart from a parallel crack distribution. The physical behaviour of fluid flow through a cracked porous material is well reproduced by the proposed model. The presence of this effective permeability coupling to analytical expression of crack growth under compression enables the modelling of the permeability variation due to stress-induced cracking in a porous rock. This incorporation allows the prediction of the permeability change of a porous rock embedding an anisotropic crack distribution from any initial crack density, that is, lower, around or upper to percolation threshold. The interaction between cracks is not explicitly taken into account. The model is well applicable both to micro- and macrocracks.

A multiscale model of distributed fracture and permeability in solids in all-round compression

NASA Astrophysics Data System (ADS)

De Bellis, Maria Laura; Della Vecchia, Gabriele; Ortiz, Michael; Pandolfi, Anna

2017-07-01

We present a microstructural model of permeability in fractured solids, where the fractures are described in terms of recursive families of parallel, equidistant cohesive faults. Faults originate upon the attainment of tensile or shear strength in the undamaged material. Secondary faults may form in a hierarchical organization, creating a complex network of connected fractures that modify the permeability of the solid. The undamaged solid may possess initial porosity and permeability. The particular geometry of the superposed micro-faults lends itself to an explicit analytical quantification of the porosity and permeability of the damaged material. The model is the finite kinematics version of a recently proposed porous material model, applied with success to the simulation of laboratory tests and excavation problems [De Bellis, M. L., Della Vecchia, G., Ortiz, M., Pandolfi, A., 2016. A linearized porous brittle damage material model with distributed frictional-cohesive faults. Engineering Geology 215, 10-24. Cited By 0. 10.1016/j.enggeo.2016.10.010]. The extension adds over and above the linearized kinematics version for problems characterized by large deformations localized in narrow zones, while the remainder of the solid undergoes small deformations, as typically observed in soil and rock mechanics problems. The approach is particularly appealing as a means of modeling a wide scope of engineering problems, ranging from the prevention of water or gas outburst into underground mines, to the prediction of the integrity of reservoirs for CO2 sequestration or hazardous waste storage, to hydraulic fracturing processes.

Thermodynamically consistent model of brittle oil shales under overpressure

NASA Astrophysics Data System (ADS)

Izvekov, Oleg

2016-04-01

The concept of dual porosity is a common way for simulation of oil shale production. In the frame of this concept the porous fractured media is considered as superposition of two permeable continua with mass exchange. As a rule the concept doesn't take into account such as the well-known phenomenon as slip along natural fractures, overpressure in low permeability matrix and so on. Overpressure can lead to development of secondary fractures in low permeability matrix in the process of drilling and pressure reduction during production. In this work a new thermodynamically consistent model which generalizes the model of dual porosity is proposed. Particularities of the model are as follows. The set of natural fractures is considered as permeable continuum. Damage mechanics is applied to simulation of secondary fractures development in low permeability matrix. Slip along natural fractures is simulated in the frame of plasticity theory with Drucker-Prager criterion.

Influence of the spatial distribution of cementation on the permeability and mechanical attributes of sedimentary and fault rocks

NASA Astrophysics Data System (ADS)

Mozley, P.; Yoon, H.; Williams, R. T.; Goodwin, L. B.

2015-12-01

The spatial distribution of pore-filling authigenic minerals (cements) is highly variable and controlled in large part by the mineralogy of the cements and host sediment grains. Two end-member distributions of cements that commonly occur in sedimentary material are: (1) concretionary, in which precipitation occurred in specific zones throughout the sediment, with intervening areas largely uncemented; and (2) grain-rimming, in which precipitation occurred on grain-surfaces relatively uniformly throughout the rock. Concretions form in rocks in which sediment grains have a different composition from the cement, whereas rim cements form in those that have the same composition. Both the mechanical attributes and permeability of a given volume of rock are affected to a much greater extent by grain rimming cements, which have a significant impact on properties at even low abundances. Concretionary cements have little impact on bulk properties until relatively large volumes have precipitated (~80% cemented) and concretions begin to link up. Precipitation of cement in fault zones also impacts both mechanical and hydrologic properties. Cementation will stiffen and strengthen unlithified sediment, thereby controlling the locus of fracturing in protolith or damage zones. Where fracture networks form in fault damage zones, they are initially high permeability elements. However, progressive cementation greatly diminishes fracture permeability, resulting in cyclical permeability variation linked to fault slip. To quantitatively describe the interactions of groundwater flow, permeability, and patterns and abundance of cements, we use pore-scale modeling of coupled fluid flow, reactive transport, and heterogeneous mineral-surface reactions. By exploring the effects of varying distributions of porosity and mineralogy, which impact patterns of cementation, we provide mechanistic explanations of the interactions of coupled processes under various flow and chemistry conditions.

Comparison of Series of Vugs and Non-vuggy Synthetic Porous Media on Formation Damage

NASA Astrophysics Data System (ADS)

Khan, H.; DiCarlo, D. A.; Prodanovic, M.

2017-12-01

Produced water reinjection (PWRI) is an established cost-effective oil field practice where produced water is injected without any cleanup, for water flooding or disposal. Resultantly the cost of fresh injection fluid and/or processing produced water is saved. A common problem with injection of unprocessed water is formation damage in the near injection zone due to solids (fines) entrapment, causing a reduction in permeability and porosity of the reservoir. Most studies have used homogeneous porous media with unimodal grain sizes, while real world porous media often has a wide range of pores, up to and including vugs in carbonaceous rocks. Here we fabricate a series of vugs in synthetic porous media by sintering glass beads with large dissolvable inclusions. The process is found to be repeatable, allowing a similar vug configuration to be tested for different flow conditions. Bi-modal glass bead particles (25 & 100 micron) are injected at two different flow rates and three different injection concentrations. Porosity, permeability and effluent concentration are determined using CT scanning, pressure measurements and particle counting (Coulter counter), respectively. Image analysis is performed on the CT images to determine the change in vug size for each flow condition. We find that for the same flow conditions, heterogeneous media with series of vugs have an equal or greater permeability loss compared to homogeneous porous media. A significant change in permeability is observed at the highest concentration and flow rate as more particles approach the filter quickly, resulting in a greater loss in permeability in the lower end of the core. Image analysis shows the highest loss in vug size occurs at the low flow rate and highest concentration. The lower vug is completely blocked for this flow case. For all flow cases lower values of porosity are observed after the core floods. At low flow rate and medium concentration, a drastic loss in porosity is observed in the lower part of the core, after the vuggy zone. This trough is also distinctly clear in the homogeneous core for the same flow conditions. This study focuses on understanding the effect of pore heterogeneity on formation damage. We conclude that more damage is done deeper in vuggy formations at high flow rates, resulting in shorter injection cycle prior to clean up.

Physicochemical basis for dilated intercellular spaces in non-erosive acid-damaged rabbit esophageal epithelium.

PubMed

Tobey, N A; Gambling, T M; Vanegas, X C; Carson, J L; Orlando, R C

2008-01-01

Dilated intercellular spaces (DIS) within esophageal epithelium (EE) is a histopathologic feature of non-erosive reflux disease and early lesion in acid-damaged rabbit EE associated with increased paracellular permeability. Its cause remains unknown, but the lesion's morphology suggests a significant fluid shift into the intercellular spaces (ICS). Since water follows osmotic forces and consequently ion movements, we explored the role of active (ion) transport and ion gradients in its pathogenesis. This was done by quantifying the effect of inhibited active transport and altered ion gradients on electrical resistance (R(T)) and ICS diameter in acid-exposed Ussing-chambered rabbit EE. Compared with normal Ringer, pH 7.5, 30 minutes of luminal HCl (100 mmol/L), pH 1.1, increased permeability (R(T): +5 +/- 4% vs-52 +/- 4%) and ICS diameter (0.25 +/- 0.01 microm vs 0.42 +/- 0.02 microm), but had no effect on cell morphology or diameter. Ouabain pretreatment significantly reduced active transport but had no effect on the acid-induced changes. However, negating the chloride gradient created by luminal HCl either by adding choline chloride, 100 mmol/L, serosally or by replacing luminal HCl, pH 1.1, with luminal H(2)SO(4), pH 1.1, prevented the development of DIS while maintaining the increase in permeability. DIS was also prevented in the presence of a 100 mmol/L (choline) chloride gradient by luminal exposure at neutral pH. DIS in HCl-damaged EE is caused by an H(+)-induced increase in epithelial permeability; this enables Cl(-) to diffuse along its gradient into the ICS, creating an osmotic force for water movement into and (hydrostatic) dilation of the ICS.

Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

PubMed

Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

2017-04-03

Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Kollidon VA64, a membrane-resealing agent, reduces histopathology and improves functional outcome after controlled cortical impact in mice.

PubMed

Mbye, Lamin H; Keles, Eyup; Tao, Luyang; Zhang, Jimmy; Chung, Joonyong; Larvie, Mykol; Koppula, Rajani; Lo, Eng H; Whalen, Michael J

2012-03-01

Loss of plasma membrane integrity is a feature of acute cellular injury/death in vitro and in vivo. Plasmalemma-resealing agents are protective in acute central nervous system injury models, but their ability to reseal cell membranes in vivo has not been reported. Using a mouse controlled cortical impact (CCI) model, we found that propidium iodide-positive (PI+) cells pulse labeled at 6, 24, or 48 hours maintained a degenerative phenotype and disappeared from the injured brain by 7 days, suggesting that plasmalemma permeability is a biomarker of fatal cellular injury after CCI. Intravenous or intracerebroventricular administration of Kollidon VA64, poloxamer P188, or polyethylene glycol 8000 resealed injured cell membranes in vivo (P<0.05 versus vehicle or poloxamer P407). Kollidon VA64 (1 mmol/L, 500 μL) administered intravenously to mice 1  hour after CCI significantly reduced acute cellular degeneration, chronic brain tissue damage, brain edema, blood-brain barrier damage, and postinjury motor deficits (all P<0.05 versus vehicle). However, VA64 did not rescue pulse-labeled PI+ cells from eventual demise. We conclude that PI permeability within 48 hours of CCI is a biomarker of eventual cell death/loss. Kollidon VA64 reduces secondary damage after CCI by mechanisms other than or in addition to resealing permeable cells.

Fault zone hydrogeologic properties and processes revealed by borehole temperature monitoring

NASA Astrophysics Data System (ADS)

Fulton, P. M.; Brodsky, E. E.

2015-12-01

High-resolution borehole temperature monitoring can provide valuable insight into the hydrogeologic structure of fault zones and transient processes that affect fault zone stability. Here we report on results from a subseafloor temperature observatory within the Japan Trench plate boundary fault. In our efforts to interpret this unusual dataset, we have developed several new methods for probing hydrogeologic properties and processes. We illustrate how spatial variations in the thermal recovery of the borehole after drilling and other spectral characteristics provide a measure of the subsurface permeability architecture. More permeable zones allow for greater infiltration of cool drilling fluids, are more greatly thermally disturbed, and take longer to recover. The results from the JFAST (Japan Trench Fast Drilling Project) observatory are consistent with geophysical logs, core data, and other hydrologic observations and suggest a permeable damage zone consisting of steeply dipping faults and fractures overlays a low-permeability clay-rich plate boundary fault. Using high-resolution time series data, we have also developed methods to map out when and where fluid advection occurs in the subsurface over time. In the JFAST data, these techniques reveal dozens of transient earthquake-driven fluid pulses that are spatially correlated and consistently located around inferred permeable areas of the fault damage zone. These observations are suspected to reflect transient fluid flow driven by pore pressure changes in response to dynamic and/or static stresses associated with nearby earthquakes. This newly recognized hydrologic phenomenon has implications for understanding subduction zone heat and chemical transport as well as the redistribution of pore fluid pressure which influences fault stability and can trigger other earthquakes.

Synergistic effects of hydrogen peroxide and ethanol on cell viability loss in PC12 cells by increase in mitochondrial permeability transition.

PubMed

Lee, Chung Soo; Kim, Yun Jeong; Ko, Hyun Hee; Han, Eun Sook

2005-07-15

The promoting effect of ethanol against the cytotoxicity of hydrogen peroxide (H2O2) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with H2O2 resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. In PC12 cells and dopaminergic neuroblastoma SH-SY5Y cells, the promoting effect of ethanol on the H2O2-induced cell death was increased with exposure time. Ethanol promoted the nuclear damage, change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to H2O2 in PC12 cells. Catalase, carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the H2O2 and ethanol-induced mitochondrial dysfunction and cell injury. The results show that the ethanol treatment promotes the cytotoxicity of H2O2 against PC12 cells. Ethanol may enhance the H2O2-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that ethanol as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by oxidants.

Fracture-permeability behavior of shale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carey, J. William; Lei, Zhou; Rougier, Esteban

The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition tomore » the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.« less

Fracture-permeability behavior of shale

DOE PAGES

Carey, J. William; Lei, Zhou; Rougier, Esteban; ...

2015-05-08

The fracture-permeability behavior of Utica shale, an important play for shale gas and oil, was investigated using a triaxial coreflood device and X-ray tomography in combination with finite-discrete element modeling (FDEM). Fractures generated in both compression and in a direct-shear configuration allowed permeability to be measured across the faces of cylindrical core. Shale with bedding planes perpendicular to direct-shear loading developed complex fracture networks and peak permeability of 30 mD that fell to 5 mD under hydrostatic conditions. Shale with bedding planes parallel to shear loading developed simple fractures with peak permeability as high as 900 mD. In addition tomore » the large anisotropy in fracture permeability, the amount of deformation required to initiate fractures was greater for perpendicular layering (about 1% versus 0.4%), and in both cases activation of existing fractures are more likely sources of permeability in shale gas plays or damaged caprock in CO₂ sequestration because of the significant deformation required to form new fracture networks. FDEM numerical simulations were able to replicate the main features of the fracturing processes while showing the importance of fluid penetration into fractures as well as layering in determining fracture patterns.« less

Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening

NASA Astrophysics Data System (ADS)

Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C.; Konofagou, Elisa E.

2015-12-01

Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r2  =  0.77) (2) the permeability of the opened BBB (r2  =  0.82) (3) the likelihood of safe opening (P  <  0.05, safe opening compared to cases of damage; P  <  0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r2  =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.

Acoustic cavitation-based monitoring of the reversibility and permeability of ultrasound-induced blood-brain barrier opening.

PubMed

Sun, Tao; Samiotaki, Gesthimani; Wang, Shutao; Acosta, Camilo; Chen, Cherry C; Konofagou, Elisa E

2015-12-07

Cavitation events seeded by microbubbles have been previously reported to be associated with MR- or fluorescent-contrast enhancement after focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening. However, it is still unknown whether bubble activity can be correlated with the reversibility (the duration of opening and the likelihood of safe reinstatement) and the permeability of opened BBB, which is critical for the clinical translation of using passive cavitation detection to monitor, predict and control the opening. In this study, the dependence of acoustic cavitation on the BBB opening duration, permeability coefficient and histological damage occurrence were thus investigated. Transcranial pulsed FUS at 1.5 MHz in the presence of systemically circulating microbubbles was applied in the mouse hippocampi (n  =  60). The stable and inertial cavitation activities were monitored during sonication. Contrast-enhanced MRI was performed immediately after sonication and every 24 h up to 6 d thereafter, to assess BBB opening, brain tissue permeability and potential edema. Histological evaluations were used to assess the occurrence of neurovascular damages. It was found that stable cavitation was well correlated with: (1) the duration of the BBB opening (r(2)  =  0.77); (2) the permeability of the opened BBB (r(2)  =  0.82); (3) the likelihood of safe opening (P  <  0.05, safe opening compared to cases of damage; P  <  0.0001, no opening compared to safe opening). The inertial cavitation dose was correlated with the resulting BBB permeability (r(2)  =  0.72). Stable cavitation was found to be more reliable than inertial cavitation at assessing the BBB opening within the pressure range used in this study. This study demonstrates that the stable cavitation response during BBB opening holds promise for predicting and controlling the restoration and pharmacokinetics of FUS-opened BBB. The stable cavitation response therefore showed great promise in predicting the BBB opening duration, enabling thus control of opening according to the drug circulation time. In addition, avoiding adverse effects in the brain and assessing the pharmacokinetics of the compounds delivered can also be achieved by monitoring and controlling the stable cavitation emissions.

Simultaneous flow of gas and water in a damage-susceptible argillaceous rock

NASA Astrophysics Data System (ADS)

Nguyen, T. S.

2011-12-01

A research project has been initiated by the Canadian Nuclear Safety Commission (CNSC) to study the influence of gas generation and migration on the long term safety of deep geological repositories for radioactive wastes. Such facilities rely on multiple barriers to isolate and contain the wastes. Depending on the level of radioactivity of the wastes, those barriers include some or all of the following: corrosion and structurally resistant containers, low permeability seals around the emplacements rooms, galleries and shaft, and finally the host rock formations. Large quantities of gas may be generated from the degradation of the waste forms or the corrosion of the containers. The generated gas pressures, if sufficiently large, can induce cracks and microcracks in the engineered and natural barriers and affect their containment functions. The author has developed a mathematical model to simulate the above effects. The model must be calibrated and validated with laboratory and field experiments in order to provide confidence in its future use for assessing the effects of gas on the long term safety of nuclear wastes repositories. The present communication describes the model and its use in the simulation of laboratory and large scale in-situ gas injection experiments in an argillaceous rock, known as Opalinus clay, from Mont Terri, Switzerland. Both the laboratory and in-situ experiments show that the gas flow rate substantially increases when the injection pressure is higher than the confining stress. The above observation seems to indicate that at high gas injection pressures, damage could possibly be induced in the rock formation resulting in an important increase in its permeability. In order to simulate the experiments, we developed a poro-elastoplastic model, with the consideration of two compressible pore fluids (water and gas). The bulk movement of the pore fluids is assumed to obey the generalized Darcy's law, and their respective degree of saturation is represented by the Van Genuchten's functions. The solid skeleton is assumed to be elastoplastic, with degradation of the strength and elastic modulus accompanied by an increase in permeability when damage is accumulated. The model can predict the three distinct flow regimes found in the experiments: a low flow regime where gas movement is restricted to the injection zone, a moderate flow regime when damage is limited, and a high flow regime when damage induces a substantial increase in the permeability.

Development of Hydrologic Characterization Technology of Fault Zones (in Japanese; English)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karasaki, Kenzi; Onishi, Tiemi; Wu, Yu-Shu

2008-03-31

Through an extensive literature survey we find that there is very limited amount of work on fault zone hydrology, particularly in the field using borehole testing. The common elements of a fault include a core, and damage zones. The core usually acts as a barrier to the flow across it, whereas the damage zone controls the flow either parallel to the strike or dip of a fault. In most of cases the damage zone isthe one that is controlling the flow in the fault zone and the surroundings. The permeability of damage zone is in the range of two tomore » three orders of magnitude higher than the protolith. The fault core can have permeability up to seven orders of magnitude lower than the damage zone. The fault types (normal, reverse, and strike-slip) by themselves do not appear to be a clear classifier of the hydrology of fault zones. However, there still remains a possibility that other additional geologic attributes and scaling relationships can be used to predict or bracket the range of hydrologic behavior of fault zones. AMT (Audio frequency Magneto Telluric) and seismic reflection techniques are often used to locate faults. Geochemical signatures and temperature distributions are often used to identify flow domains and/or directions. ALSM (Airborne Laser Swath Mapping) or LIDAR (Light Detection and Ranging) method may prove to be a powerful tool for identifying lineaments in place of the traditional photogrammetry. Nonetheless not much work has been done to characterize the hydrologic properties of faults by directly testing them using pump tests. There are some uncertainties involved in analyzing pressure transients of pump tests: both low permeability and high permeability faults exhibit similar pressure responses. A physically based conceptual and numerical model is presented for simulating fluid and heat flow and solute transport through fractured fault zones using a multiple-continuum medium approach. Data from the Horonobe URL site are analyzed to demonstrate the proposed approach and to examine the flow direction and magnitude on both sides of a suspected fault. We describe a strategy for effective characterization of fault zone hydrology. We recommend conducting a long term pump test followed by a long term buildup test. We do not recommend isolating the borehole into too many intervals. We do recommend ensuring durability and redundancy for long term monitoring.« less

Micro-Raman spectroscopy study of the effect of Mid-Ultraviolet radiation on erythrocyte membrane.

PubMed

Li, N; Li, S X; Guo, Z Y; Zhuang, Z F; Li, R; Xiong, K; Chen, S J; Liu, S H

2012-07-02

Mid-Ultraviolet (UVB) has a significant influence on human health. In this study, human erythrocytes were exposed to UVB to investigate the effects of UVB radiation on erythrocytes membrane. And Micro-Raman spectroscopy was employed to detect the damage. Principal component analysis (PCA) was used to classify the control erythrocytes and the irradiated erythrocytes. Results showed that the erythrocytes membrane was damaged by Mid-Ultraviolet (UVB) radiation. The intensity of the Raman peaks at 1126 cm(-1) and 1082 cm(-1) were used to calculate the Longitudinal Order-Parameters in Chains (S(trans)) which can present the liquidity and ionic permeability of erythrocyte membrane. After UVB radiation for 30 min, both the liquidity and ionic permeability decreased. At the same time, the intensity of the peaks at 1302 cm(-1) (α-helix), 1254 cm(-1) (random coil), 1452 cm(-1) and 1430 cm(-1) (CH(2)/CH(3) stretch) have also changed which indicated the membrane protein also been damaged by UVB. In the whole process of radiation, the more UVB radiation dose the more damage on the erythrocyte membrane. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of Streptomycin Administration on Increases in Skeletal Muscle Fiber Permeability and Size Following Eccentric Muscle Contractions.

PubMed

Hayao, Keishi; Tamaki, Hiroyuki; Nakagawa, Kouki; Tamakoshi, Keigo; Takahashi, Hideaki; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

2018-06-01

The purpose of this study was to investigate the preventive effect of streptomycin (Str) administration on changes in membrane permeability and the histomorphological characteristics of damaged muscle fibers following eccentric contraction (ECC ). Eighteen 7-week-old male Fischer 344 rats were randomly assigned to three groups: control (Cont), ECC, and ECC with Str (ECC + Str). The tibialis anterior (TA) muscles in both ECC groups were stimulated electrically and exhibited ECC. Evans blue dye (EBD), a marker of muscle fiber damage associated with increased membrane permeability, was injected 24 hr before TA muscle sampling. The number of EBD-positive fibers, muscle fiber cross-sectional area (CSA), and roundness were determined via histomorphological analysis. The ECC intervention resulted in an increased fraction of EBD-positive fibers, a larger CSA, and decreased roundness. The fraction of EBD-positive fibers was 79% lower in the ECC + Str group than in the ECC group. However, there was no difference in the CSA and roundness of the EBD-positive fibers between the two ECC groups. These results suggest that Str administration can reduce the number of myofibers that increase membrane permeability following ECC, but does not ameliorate the extent of fiber swelling in extant EBD-positive fibers. Anat Rec, 301:1096-1102, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Development of an ion-pair to improve the colon permeability of a low permeability drug: Atenolol.

PubMed

Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

2016-10-10

To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation. Copyright © 2016 Elsevier B.V. All rights reserved.

Pathogenesis of NSAID-induced gastric damage: Importance of cyclooxygenase inhibition and gastric hypermotility

PubMed Central

Takeuchi, Koji

2012-01-01

This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase in mucosal permeability, neutrophil infiltration and oxyradical production, and eventually producing gastric lesions. These lesions are prevented by pretreatment with PGE2 and antisecretory drugs, and also via an atropine-sensitive mechanism, not related to antisecretory action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach, the combined administration of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases prostaglandin E2 (PGE2) production and causes gastric hypermotility and an increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions, including adrenalectomy, arthritis, and Helicobacter pylori-infection. In summary, gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility, and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition. PMID:22611307

Pretreatment Blood Brain Barrier Damage and Post Treatment Intracranial Hemorrhage in Patients Receiving IV tPA

PubMed Central

Leigh, Richard; Jen, Shyian S.; Hillis, Argye E.; Krakauer, John W.; Barker, Peter B.

2014-01-01

Background and Purpose Early blood brain barrier (BBB) damage after acute ischemic stroke (AIS) has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of BBB damage evident on pre-tPA MRI scans was related to the degree of post-tPA ICH in patients with AIS. Methods Analysis was performed on a database of patients with AIS provided by the STIR and VISTA Imaging Investigators. Patients with perfusion-weighted imaging (PWI) lesions >10mL and negative gradient-recalled echo (GRE) imaging prior to IV tPA were included. Post processing of the PWI source images was performed to estimate changes in BBB permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up GRE images were reviewed for evidence of ICH and divided into three groups according to ECASS criteria: no hemorrhage (NH), hemorrhagic infarction (HI), and parenchymal hematoma (PH). Results 75 patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as HI, and nine were classified as PH. The mean permeability (±standard deviations), expressed as an index of contrast leakage, was 17.0%±8.8 in the NH group, 19.4%±4.0 in the HI group, and 24.6%±4.5 in the PH group. Permeability was significantly correlated with ICH grade in univariate (p=0.007) and multivariate (p=0.008) linear regression modeling. Conclusions A PWI-derived index of BBB damage measured prior to IV tPA is associated with the severity of ICH after treatment in patients with AIS. PMID:24876245

Structural architecture and petrophysical properties of the Rocca di Neto extensional fault zone developed in the shallow marine sediments of the Crotone Basin (Southern Apennines, Italy).

NASA Astrophysics Data System (ADS)

Pizzati, Mattia; Balsamo, Fabrizio; Iacumin, Paola; Swennen, Rudy; Storti, Fabrizio

2017-04-01

In this contribution we describe the architecture and petrophysical properties of the Rocca di Neto extensional fault zone in loose and poorly lithified sediments, located in the Crotone forearc basin (south Italy). To this end, we combined fieldwork with microstructural observations, grain size analysis, and in situ permeability measurements. The studied fault zone has an estimated maximum displacement of 80-90 m and separates early Pleistocene age (Gelasian) sands in the footwall from middle Pleistocene (Calabrian) silty clay in the hangingwall. The analysed outcrop consists of about 70 m section through the fault zone mostly developed in the footwall block. Fault zone consists of four different structural domains characterized by distinctive features: (1) <1 m-thick fault core (where the majority of the displacement is accommodated) in which bedding is transposed into foliation imparted by grain preferential orientation and some black gouges decorate the main slip surfaces; (2) zone of tectonic mixing characterized by a set of closely spaced and anastomosed deformation bands parallel to the main slip surface; (3) about 8 m-thick footwall damage zone characterized by synthetic and antithetic sets of deformation bands; (4) zone of background deformation with a few, widely-spaced conjugate minor faults and deformation bands. The boundary between the relatively undeformed sediments and the damage zone is not sharp and it is characterized by a progressive decrease in deformation intensity. The silty clay in the hangingwall damage zone is characterized by minor faults. Grain size and microstructural data indicate that particulate flow with little amount of cataclasis is the dominant deformation mechanism in both fault core rocks and deformation bands. Permeability of undeformed sediments is about 70000 mD, whereas the permeability in deformation bands ranges from 1000 to 18000 mD; within the fault core rocks permeability is reduced up to 3-4 orders of magnitude respect to the undeformed domains. Structural and petrophysical data suggest that the Rocca di Neto fault zone may compartmentalize the footwall block due to both juxtaposition of clay-rich lithology in the hangingwall and the development of low permeability fault core rocks.

Application of a Novel Murine Ear Vein Model to Evaluate the Effects of a Vascular Radioprotectant on Radiation-Induced Vascular Permeability and Leukocyte Adhesion.

PubMed

Ashcraft, Kathleen A; Choudhury, Kingshuk Roy; Birer, Sam R; Hendargo, Hansford C; Patel, Pranalee; Eichenbaum, Gary; Dewhirst, Mark W

2018-04-19

Vascular injury after radiation exposure contributes to multiple types of tissue injury through a cascade of events. Some of the earliest consequences of radiation damage include increased vascular permeability and promotion of inflammation, which is partially manifested by increased leukocyte-endothelial (L/E) interactions. We describe herein a novel intravital imaging method to evaluate L/E interactions, as a function of shear stress, and vascular permeability at multiple time points after local irradiation to the ear. This model permitted analysis of quiescent vasculature that was not perturbed by any surgical manipulation prior to imaging. To evaluate the effects of radiation on vascular integrity, fluorescent dextran was injected intravenously and its extravasation in the extravascular space surrounding the ear vasculature was measured at days 3 and 7 after 6 Gy irradiation. The vascular permeability rate increased approximately twofold at both days 3 and 7 postirradiation ( P < 0.05). Leukocyte rolling, which is indicative of L/E interactions, was significantly increased in mice at 24 h postirradiation compared to that of nonirradiated mice. To assess our model, as a means for assessing vascular radioprotectants, we treated additional cohorts of mice with a thrombopoietin mimetic, TPOm (RWJ-800088). In addition to stimulating platelet formation, thrombopoietin can protect vasculature after several forms of injury. Thus, we hypothesized that TPOm would reduce vascular permeability and L/E adhesion after localized irradiation to the ear vasculature of mice. If TPOm reduced these consequences of radiation, it would validate the utility of our intravital imaging method. TPOm reduced radiation-induced vascular leakage to control levels at day 7. Furthermore, L/E cell interactions were also reduced in irradiated mice treated with TPOm, compared with mice receiving irradiation alone, particularly at high shear stress ( P = 0.03, Kruskal-Wallis). We conclude that the ear model is useful for monitoring quiescent normal tissue vascular injury after radiation exposure. Furthermore, the application of TPOm, for preventing early inflammatory response created by damage to vascular endothelium, suggests that this drug may prove useful in reducing toxicities from radiotherapy, which damage microvasculature that critically important to tissue function.

Normobaric Hyperoxia Reduces Blood Occludin Fragments in Rats and Patients With Acute Ischemic Stroke.

PubMed

Shi, Shuhai; Qi, Zhifeng; Ma, Qingfeng; Pan, Rong; Timmins, Graham S; Zhao, Yongmei; Shi, Wenjuan; Zhang, Yunzhou; Ji, Xunming; Liu, Ke Jian

2017-10-01

Damage of the blood-brain barrier (BBB) increases the incidence of neurovascular complications, especially for cerebral hemorrhage after tPA (tissue-type plasminogen activator) therapy. Currently, there is no effective method to evaluate the extent of BBB damage to guide tPA use. Herein, we investigated whether blood levels of tight junction proteins could serve as biomarker of BBB damages in acute ischemic stroke (AIS) in both rats and patients. We examined whether this biomarker could reflect the extent of BBB permeability during cerebral ischemia/reperfusion and the effects of normobaric hyperoxia (NBO) on BBB damage. Rats were exposed to NBO (100% O 2 ) or normoxia (21% O 2 ) during middle cerebral artery occlusion. BBB permeability was determined. Occludin and claudin-5 in blood and cerebromicrovessels were measured. Patients with AIS were assigned to oxygen therapy or room air for 4 hours, and blood occludin and claudin-5 were measured at different time points after stroke. Cerebral ischemia/reperfusion resulted in the degradation of occludin and claudin-5 in microvessels, leading to increased BBB permeability in rats. In blood samples, occludin increased with 4-hour ischemia and remained elevated during reperfusion, correlating well with its loss from ischemic cerebral microvessels. NBO treatment both prevented occludin degradation in microvessels and reduced occludin levels in blood, leading to improved neurological functions in rats. In patients with AIS receiving intravenous tPA thrombolysis, the blood occludin was already elevated when patients arrived at hospital (within 4.5 hours since symptoms appeared) and remained at a high level for 72 hours. NBO significantly lowered the level of blood occludin and improved neurological functions in patients with AIS. Blood occludin may be a clinically viable biomarker for evaluating BBB damage during ischemia/reperfusion. NBO therapy has the potential to reduce blood occludin, protect BBB, and improve outcome in AIS patients with intravenous tPA thrombolysis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02974283. © 2017 American Heart Association, Inc.

Axial and Radial Permeability Evolutions of Compressed Sandstones: End Effects and Shear-band Induced Permeability Anisotropy

NASA Astrophysics Data System (ADS)

Dautriat, Jeremie; Gland, Nicolas; Guelard, Jean; Dimanov, Alexandre; Raphanel, Jean L.

2009-07-01

The influence of hydrostatic and uniaxial stress states on the porosity and permeability of sandstones has been investigated. The experimental procedure uses a special triaxial cell which allows permeability measurements in the axial and radial directions. The core sleeve is equipped with two pressure samplers placed distant from the ends. They provide mid-length axial permeability measure as opposed to the overall permeability measure, which is based on the flow imposed through the pistons of the triaxial cell. The core sleeve is also equipped to perform flows in two directions transverse to the axis of the sample. Two independent measures of axial and complementary radial permeability are thus obtained. Both Fontainebleau sandstone specimens with a porosity of about 5.8% to 8% and low permeability ranging from 2.5 mD to 30 mD and Bentheimer sandstone with a porosity of 24% and a high permeability of 3 D have been tested. The initial axial permeability values obtained by each method are in good agreement for the Fontainebleau sandstone. The Bentheimer sandstone samples present an axial mid-length permeability 1.6 times higher than the overall permeability. A similar discrepancy is also observed in the radial direction, also it relates essentially to the shape of flow lines induced by the radial flow. All the tested samples have shown a higher stress dependency of overall and radial permeability than mid-length permeability. The effect of compaction damage at the pistons/sample and radial ports/sample interfaces is discussed. The relevance of directional permeability measurements during continuous uniaxial compression loadings has been shown on the Bentheimer sandstone until the failure of the sample. We can efficiently measure the influence of brittle failure associated to dilatant regime on the permeability: It tends to increase in the failure propagation direction and to decrease strongly in the transverse direction.

Numerical Modeling, Thermomechanical Testing, and NDE Procedures for Prediction of Microcracking Induced Permeability of Cryogenic Composites

NASA Technical Reports Server (NTRS)

Noh, Jae; Whitcomb, John; Oh, Bongtaek; Lagoudas, Dimitris; Maslov, Konstatin; Ganpatyre, Atul; Kinra, Vikram

2003-01-01

Reusable Space Vehicles will include light cryogenic composite fuel tanks that must not leak excessively even after multiple launches. Damage in cryogenic composite fuel tanks induced during manufacturing and advanced by thermomechanical cycling can accelerate leakage of the propellant. Whether the leakage exceeds tolerable levels depends on many factors, including pressure gradients, microcrack density, other damage such as delamination, connectivity of the cracks, residual stresses from manufacture, service-induced stresses from thermal and mechanical loads, and composite lay-up. Although it is critical to experimentally characterize permeability during various thermal and mechanical load histories, optimal design depends on having analytical models that can predict the effect of various parameters on performance. Our broad goal is to develop such models that are experimentally validated by destructive and non-destructive evaluation means.

Transmural Intestinal Wall Permeability in Severe Ischemia after Enteral Protease Inhibition

PubMed Central

Altshuler, Angelina E.; Lamadrid, Itze; Li, Diana; Ma, Stephanie R.; Kurre, Leena; Schmid-Schönbein, Geert W.; Penn, Alexander H.

2014-01-01

In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases) and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein) in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP) inhibitors (doxycycline, GM 6001), and serine protease inhibitor (tranexamic acid) in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation) for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid) did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen across the wall and enteral proteolytic inhibition attenuates tissue breakdown. These combined interventions ameliorate lesion formation in the small intestine after hemorrhagic shock. PMID:24805256

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

PubMed

Salmon, Andrew H J; Satchell, Simon C

2012-03-01

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function/dysfunction, such as mechanotransduction, leukocyte-endothelial interactions and the development of atherosclerosis, indicate that alterations in the endothelial glycocalyx may also be playing a role in the dysfunction of other organs observed in these disease states. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Intestinal fatty acid-binding protein and gut permeability responses to exercise.

PubMed

March, Daniel S; Marchbank, Tania; Playford, Raymond J; Jones, Arwel W; Thatcher, Rhys; Davison, Glen

2017-05-01

Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Two-way repeated measures ANOVA revealed an arm × time interaction for L/R and I-FABP (P < 0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P < 0.001) and Col (148% of pre, P < 0.001) with post-exercise values significantly lower with Col (P < 0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P = 0.002) but not in the Col arm (107%, P = 0.862) with post-exercise values significantly lower with Col (P = 0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P = 0.044) but not visit two (P = 0.200) although overall plots/patterns do appear similar for each. These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute.

Spatial variability of damage around faults in the Joe Lott Tuff Member of the Mount Belknap Volcanics, southwestern Utah: An analog to faulting in tuff on Mars

NASA Astrophysics Data System (ADS)

Okubo, C. H.

2011-12-01

The equatorial layered deposits on Mars exhibit abundant evidence for the sustained presence of groundwater, and therefore insight into past water-related processes may be gained through the study of these deposits. Pyroclastic and evaporitic sediments are two broad lithologies that are known or inferred to comprise these deposits. Investigations into the effects of faulting on fluid flow potential through such Mars analog lithologies have been limited. Thus a study into the effects of faulting on fluid flow pathways through fine-grained pyroclastic sediments has been undertaken, and the results of this study are presented here. Faults and their damage zones can influence the trapping and migration of fluids by acting as either conduits or barriers to fluid flow. In clastic sedimentary rocks, the conductivity of fault damage zones is primarily a function of the microstructure of the host rock, stress history, phyllosilicate content, and cementation. The chemical composition of the host rock influences the mechanical strength of the grains, the susceptibility of the grains to alteration, and the availability of authigenic cements. The spatial distribution of fault-related damage is investigated within the Joe Lott Tuff Member of the Mount Belknap Volcanics, Utah. Damage is characterized by measuring fracture densities along the fault, and by mapping the gas permeability of the surrounding rock. The Joe Lott Tuff is a partially welded, crystal-poor, rhyolite ash-flow tuff of Miocene age. While the rhyolitic chemical composition of the Joe Lott Tuff is not analogous to the basaltic compositions expected for Mars, the mechanical behavior of a poorly indurated mixture of fine-grained glass and pumice is pertinent to understanding the fundamental mechanics of faulting in Martian pyroclastic sediments. Results of mapping around two faults are presented here. The first fault is entirely exposed in cross-section and has a down-dip height of ~10 m. The second fault is partially exposed, with ~21 m visible in cross-section. Both faults have a predominantly normal sense of offset and a minor dextral strike-slip component. The 10 m fault has a single well-defined surface, while the 21 m fault takes the form of a 5-10 cm wide fault core. Fracture density at the 10 m fault is highest near its upper and lower tips, forming distinct near-tip fracture damage zones. At the 21 m fault, fracture density is broadly consistent along the exposed height of the fault, with the highest fracture densities nearest to the fault core. Fracture density is higher in the hanging walls than in the footwalls of both faults, and the footwall of the 21 m fault exhibits m-scale areas of significant distributed cataclasis. Gas permeability has a marked decrease, several orders of magnitude relative to the non-deformed host rock, at 1.5 m on either side of the 10 m fault. Permeability is lowest outboard of the fault's near-tip fracture damage zones. A similar permeability drop occurs at 1-5 m from the center of the 21 m fault's core, with the permeability drop extending furthest from the fault core in the footwall. These findings will be used to improve existing numerical methods for predicting subsurface fluid flow patterns from observed fault geometries on Mars.

Identification of sandstone core damage using scanning electron microscopy

NASA Astrophysics Data System (ADS)

Ismail, Abdul Razak; Jaafar, Mohd Zaidi; Sulaiman, Wan Rosli Wan; Ismail, Issham; Shiunn, Ng Yinn

2017-12-01

Particles and fluids invasion into the pore spaces causes serious damage to the formation, resulting reduction in petroleum production. In order to prevent permeability damage for a well effectively, the damage mechanisms should be identified. In this study, water-based drilling fluid was compared to oil-based drilling fluids based on microscopic observation. The cores were damaged by several drilling fluid systems. Scanning electron microscope (SEM) was used to observe the damage mechanism caused by the drilling fluids. Results showed that the ester based drilling fluid system caused the most serious damage followed by synthetic oil based system and KCI-polymer system. Fine solids and filtrate migration and emulsion blockage are believed to be the major mechanisms controlling the changes in flow properties for the sandstone samples.

Acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity.

PubMed

Craven, Melanie; Chandler, Marge L; Steiner, Jörg M; Farhadi, Ashkan; Welsh, Elizabeth; Pratschke, Kathryn; Shaw, Darren J; Williams, David A

2007-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to dogs for their analgesic, antipyretic, and anti-inflammatory properties. Their beneficial actions can be offset by gastrointestinal (GI) toxicosis. Endoscopy has traditionally been employed to detect GI lesions, but alterations in GI permeability precede the development of mucosal damage. Carprofen and meloxicam alter GI permeability and mucosal absorptive capacity of dogs. Twenty adult dogs treated with an NSAID for >7 days were evaluated by permeability tests while receiving either carprofen (10 dogs) or meloxicam (10 dogs). Prospective, longitudinal observational study. A 6-sugar permeability test (sucrose, lactulose, rhamnose, 3-O-methyl-D-glucose, D-xylose, and sucralose) was performed on the day before NSAID treatment, and after 3 and 8 days of treatment. There were no significant differences in the urinary recovery ratios of lactulose: rhamnose, D-xylose: 3-O-methyl-D-glucose, or sucralose recovery within either group at any time during the study. Sucrose permeability in the meloxicam group did not alter significantly over time. However, sucrose permeability in the carprofen group decreased significantly by day 3 (P = .049) and increased again by day 8 (P = .049), to a level that was not significantly different to permeability before treatment (P = .695). The absence of increased GI permeability and diminished mucosal absorptive capacity in this group of dogs does not support the development of acute GI toxicosis during treatment with either meloxicam or carprofen.

The role of water in the recovery of microcrack damage, permeability and seismic wave speeds in limestone

NASA Astrophysics Data System (ADS)

Brantut, N.

2015-12-01

Limestone samples were deformed up to 5% inelastic axial strain at an effective confining pressure P_{eff}=50 MPa, in the cataclastic flow regime, and subsequently maintained under constant static stress conditions for extended periods of time while elastic wave speeds and permeability were continously monitored. During deformation, both seismic wave speeds and permeability decrease with increasing strain, due to the growth of sub-vertical microcracks and inelastic porosity reduction. During the static hold period under water-satured conditions, the seismic wave speeds recovered gradually, typically by around 5% (relative to their initial value) after two days, while permeability remained constant. The recovery in wave speed increases with increasing confining pressure, but decreases with increasing applied differential stress. The recovery is markedly lower when the samples are saturated with an inert fluid as opposed to water. The evolution in wave speed is interpreted quantitatively in terms of microcrack density, which shows that the post-deformation recovery is associated with an decrease in effective microcrack length, typically of the order to 10% after two days. The proposed mechanism for the observed damage recovery is microcrack closure due to a combination of backsliding on wing cracks driven by time-dependent friction and closure due to pressure-solution at contacts between propping particles or asperities and microcrack walls. The recovery rates observed in the experiments, and the proposed underlying mechanisms, are compatible with seismological observations of seismic wave speed recovery along faults following earthquakes.

Effects of electromagnetic pulse irradiation on the mouse blood-testicle barrier.

PubMed

Hou, Wu-Gang; Zhao, Jie; Li, Zhen; Li, Wei; Li, Teng; Xiong, Li-Ze; Zhang, Yuan-Qiang

2012-07-01

To investigate the effects of electromagnetic pulse irradiation on the mouse blood-testicle barrier (BTB) and spermatogenesis. After whole body irradiation with 400 kV/m electromagnetic pulse irradiation, the mouse testicles and BTB permeability were observed using hematoxylin-eosin, Evans blue, and lanthanum nitrate as tracers. The expression of the BTB tight junction protein occludin was examined using real-time polymerase chain reaction and Western blotting. At 1, 7, and 14 days after irradiation, the BTB structure was damaged, the BTB permeability was significantly increased, numerous apoptotic or necrotic spermatogenic cells were found in the lumen, and the mRNA and protein expression levels of occludin were markedly decreased. The BTB structure and occludin expression levels had gradually recovered by 21 and 28 days after irradiation. Electromagnetic pulse irradiation damaged the structure and function of mouse BTB, resulting in apoptosis or necrosis of the spermatogenic cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Permeability Evolution With Shearing of Simulated Faults in Unconventional Shale Reservoirs

NASA Astrophysics Data System (ADS)

Wu, W.; Gensterblum, Y.; Reece, J. S.; Zoback, M. D.

2016-12-01

Horizontal drilling and multi-stage hydraulic fracturing can lead to fault reactivation, a process thought to influence production from extremely low-permeability unconventional reservoir. A fundamental understanding of permeability changes with shear could be helpful for optimizing reservoir stimulation strategies. We examined the effects of confining pressure and frictional sliding on fault permeability in Eagle Ford shale samples. We performed shear-flow experiments in a triaxial apparatus on four shale samples: (1) clay-rich sample with sawcut fault, (2) calcite-rich sample with sawcut fault, (3) clay-rich sample with natural fault, and (4) calcite-rich sample with natural fault. We used pressure pulse-decay and steady-state flow techniques to measure fault permeability. Initial pore and confining pressures are set to 2.5 MPa and 5.0 MPa, respectively. To investigate the influence of confining pressure on fault permeability, we incrementally raised and lowered the confining pressure and measure permeability at different effective stresses. To examine the effect of frictional sliding on fault permeability, we slide the samples four times at a constant shear displacement rate of 0.043 mm/min for 10 minutes each and measure fault permeability before and after frictional sliding. We used a 3D Laser Scanner to image fault surface topography before and after the experiment. Our results show that frictional sliding can enhance fault permeability at low confining pressures (e.g., ≥5.0 MPa) and reduce fault permeability at high confining pressures (e.g., ≥7.5 MPa). The permeability of sawcut faults almost fully recovers when confining pressure returns to the initial value, and increases with sliding due to asperity damage and subsequent dilation at low confining pressures. In contrast, the permeability of natural faults does not fully recover. It initially increases with sliding, but then decreases with further sliding most likely due to fault gouge blocking fluid pathways.

Permeability of sediment cores from methane hydrate deposit in the Eastern Nankai Trough, Japan

NASA Astrophysics Data System (ADS)

Konno, Y.; Yoneda, J.; Egawa, K.; Ito, T.; Jin, Y.; Kida, M.; Suzuki, K.; Nakatsuka, Y.; Nagao, J.

2013-12-01

Effective and absolute permeability are key parameters for gas production from methane-hydrate-bearing sandy sediments. Effective and/or absolute permeability have been measured using methane-hydrate-bearing sandy cores and clayey and silty cores recovered from Daini Atsumi Knoll in the Eastern Nankai Trough during the 2012 JOGMEC/JAPEX Pressure coring operation. Liquid-nitrogen-immersed cores were prepared by rapid depressurization of pressure cores recovered by a pressure coring system referred to as the Hybrid PCS. Cores were shaped cylindrically on a lathe with spraying of liquid nitrogen to prevent hydrate dissociation. Permeability was measured by a flooding test or a pressure relaxation method under near in-situ pressure and temperature conditions. Measured effective permeability of hydrate-bearing sediments is less than tens of md, which are order of magnitude less than absolute permeability. Absolute permeability of clayey cores is approximately tens of μd, which would perform a sealing function as cap rocks. Permeability reduction due to a swelling effect was observed for a silty core during flooding test of pure water mimicking hydrate-dissociation-water. Swelling effect may cause production formation damage especially at a later stage of gas production from methane hydrate deposits. This study was financially supported by the Research Consortium for Methane Hydrate Resources in Japan (MH21 Research Consortium) that carries out Japan's Methane Hydrate R&D Program conducted by the Ministry of Economy, Trade and Industry (METI).

Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences

PubMed Central

Purohit, Vishnudutt; Bode, J. Christian; Bode, Christiane; Brenner, David A.; Choudhry, Mashkoor A.; Hamilton, Frank; Kang, Y. James; Keshavarzian, Ali; Rao, Radhakrishna; Sartor, R. Balfour; Swanson, Christine; Turner, Jerrold R.

2008-01-01

This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram negative bacteria in the intestine which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, L-glutamine, oats supplementation, or zinc thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries. PMID:18504085

Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

PubMed

Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

2015-01-01

Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing to curtail transcapillary albumin leakage and resulting in increasingly positive net fluid balances. GIPS may represent a third hit after the initial insult and the ischaemia reperfusion injury. Novel markers like the capillary leak index, extravascular lung water and pulmonary permeability index may help the clinician in guiding appropriate fluid management. Capillary leak is an inflammatory condition with diverse triggers that results from a common pathway that includes ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function. Fluid overload should be avoided in this setting.

Fluid leakage through fractures in an impervious caprock embedded between two geologic aquifers

NASA Astrophysics Data System (ADS)

Selvadurai, A. P. S.

2012-06-01

The paper develops an analytical result for the flow through a single fracture under a hydraulic gradient between the two aquifer regions and takes into account permeability characteristics of all components of the system. Non-dimensional results are presented to illustrate the influence of the permeability mis-match between the two geologic formations and the permeability and geometry of the fracture on the flow rate through the fracture. The analytical result is then used to develop additional results for leakage through a swarm of vertically aligned hydraulically non-interacting fractures and a damaged region containing a densely spaced array of vertically aligned fractures and worm hole type features in the caprock. The work presents a convenient result for the estimation of leakage from storage formations in geoenvironmental applications.

Effects of dexamethasone on angiotensin II-induced changes of monolayer permeability and F-actin distribution in glomerular endothelial cells.

PubMed

Fang, Junyan; Wang, Miao; Zhang, Wei; Wang, Yingdeng

2013-11-01

The aim of this study was to investigate the changes in monolayer permeability and F-actin distribution caused by angiotensin II (Ang II)-induced injury in glomerular endothelial cells (GENCs) and the effects of dexamethasone on these changes. GENCs isolated and cultured from Wistar rats were used to examine the changes in monolayer permeability and F-actin distribution induced by Ang II. GENC permeability was evaluated by measuring the diffusion of biotin-conjugated bovine serum albumin (biotin-BSA) across a cell monolayer. The expression levels and distribution of F-actin were assessed by flow cytometry. The biotin-BSA concentrations were measured by capture enzyme-linked immunosorbent assay. Ang II at a concentration of 10 mg/l increased the permeability of the GENC monolayer at 6 h and 12 h (P<0.05 and P<0.01, respectively) and caused F-actin depolymerisation at 6 h and 12 h (P<0.01). The two effects attributed to Ang II were significantly inhibited by dexamethasone treatment (P<0.01). The increased permeability of the GENC monolayer induced by Ang II was significantly correlated with the depolymerisation of F-actin. Dexamethasone abrogated the Ang II-mediated damage to GENCs indicating that it may play an important role in protecting GENCs from injury.

Urban evaporation rates for water-permeable pavements.

PubMed

Starke, P; Göbel, P; Coldewey, W G

2010-01-01

In urban areas the natural water balance is disturbed. Infiltration and evaporation are reduced, resulting in a high surface runoff and a typical city climate, which can lead to floods and damages. Water-permeable pavements have a high infiltration rate that reduces surface runoff by increasing the groundwater recharge. The high water retention capacity of the street body of up to 51 l/m(2) and its connection via pores to the surface lead to higher evaporation rates than impermeable surfaces. A comparison of these two kinds of pavements shows a 16% increase in evaporation levels of water-permeable pavements. Furthermore, the evaporation from impermeable pavements is linked directly to rain events due to fast-drying surfaces. Water-permeable pavements show a more evenly distributed evaporation after a rain event. Cooling effects by evaporative heat loss can improve the city climate even several days after rain events. On a large scale use, uncomfortable weather like sultriness or dry heat can be prevented and the urban water balance can be attenuated towards the natural.

Aluminum and temperature alteration of cell membrane permeability of Quercus rubra

DOE Office of Scientific and Technical Information (OSTI.GOV)

Junping Chen; Sucoff, E.I.; Stadelmann, E.J.

1991-06-01

Al toxicity is the major factor limiting plant growth in acid soils. This report extends research on Al-induced changes in membrane behavior of intact root cortex cells of Northern red oak (Quercus rubra). Membrane permeability was determined by the plasmometric method for individual intact cells at temperatures from 2 or 4 to 35 C. Al (0.37 millimolar) significantly increased membrane permeability to urea and monoethyl urea and decreased permeability to water. Al significantly altered the activation energy required to transport water (+ 32%), urea (+ 9%), and monoethyl urea ({minus}7%) across cell membranes. Above 9 C, Al increased the lipidmore » partiality of the cell membranes; below 7 C, Al decreased it. Al narrowed by 6 C the temperature range over which plasmolysis occurred without membrane damage. These changes in membrane behavior are explainable if Al reduced membrane lipid fluidity and kink frequency and increases packing density and the occurrence of straight lipid chains.« less

Effect on moisture permeability of typewriting on unit dose package surfaces.

PubMed

Rackson, J T; Zellhofer, M J; Birmingham, P H

1984-10-01

The effects of typewriting on labels of two unit dose packages with respect to moisture permeability were examined. Using an electric typewriter, a standard label format was imprinted on two different types of class A unit dose packages: (1) a heat-sealed paper-backed foil and cellofilm strip pouch, and (2) a copolyester and polyethylene multiple-cup blister with a heat-sealed paper-backed foil and cellofilm cover. The labels were typed at various typing-element impact settings. The official USP test for water permeation was then performed on typed packages and untyped control packages. The original untyped packages were confirmed to be USP class A quality. The packages for which successively harder impact settings were used showed a corresponding increase in moisture permeability. This resulted in a lowering of USP package ratings from class A to class B and D, some of which would be unsuitable for use in any unit dose system under current FDA repackaging standards. Typing directly onto the label of a unit dose package before it is sealed will most likely damage the package and possibly make it unfit for use. Pharmacists who must type labels for the unit dose packages studied should use the lowest possible typewriter impact setting and test for damage using the USP moisture-permeation test.

Apigenin induced apoptosis in esophageal carcinoma cells by destruction membrane structures.

PubMed

Zhu, Haiyan; Jin, Hua; Pi, Jiang; Bai, Haihua; Yang, Fen; Wu, Chaomin; Jiang, Jinhuan; Cai, Jiye

2016-07-01

Apigenin has shown to have killing effects on some kinds of solid tumor cells. However, the changes in cell membrane induced by apigenin on subcellular- or nanometer-level were still unclear. In this work, human esophageal cancer cells (EC9706 and KYSE150 cells) were employed as cell model to detect the cytotoxicity of apigenin, including cell growth inhibition, apoptosis induction, membrane toxicity, etc. MTT assay showed that apigenin could remarkably inhibit the growth and proliferation in both types of cells. Annexin V/PI-based flow cytometry analysis showed that the cytotoxic effects of apigenin in KYSE150 cells were mainly through early apoptosis induction, while in EC9706 cells, necrosis, and apoptosis were both involved in cell death. The morphological and ultrastructural properties induced by apigenin were investigated at single cellular- or nanometer-level using atomic force microscopy (AFM). Additionally, lactate dehydrogenase (LDH) leakage was measured to assess the changes in membrane permeability. The results indicated that apigenin increased the membrane permeability and caused leakage of LDH, which was consistent with damages on membrane ultrastructure detected by AFM. Therefore, membrane toxicity, including membrane ultrastructure damages and enhanced membrane permeability, played vital roles in apigenin induced human esophageal cancer cell apoptosis. SCANNING 38:322-328, 2016. © 2015 Wiley Periodicals, Inc. © Wiley Periodicals, Inc.

Limestone characterization to model damage from acidic precipitation: Effect of pore structure on mass transfer

USGS Publications Warehouse

Leith, S.D.; Reddy, M.M.; Irez, W.F.; Heymans, M.J.

1996-01-01

The pore structure of Salem limestone is investigated, and conclusions regarding the effect of the pore geometry on modeling moisture and contaminant transport are discussed based on thin section petrography, scanning electron microscopy, mercury intrusion porosimetry, and nitrogen adsorption analyses. These investigations are compared to and shown to compliment permeability and capillary pressure measurements for this common building stone. Salem limestone exhibits a bimodal pore size distribution in which the larger pores provide routes for convective mass transfer of contaminants into the material and the smaller pores lead to high surface area adsorption and reaction sites. Relative permeability and capillary pressure measurements of the air/water system indicate that Salem limestone exhibits high capillarity end low effective permeability to water. Based on stone characterization, aqueous diffusion and convection are believed to be the primary transport mechanisms for pollutants in this stone. The extent of contaminant accumulation in the stone depends on the mechanism of partitioning between the aqueous and solid phases. The described characterization techniques and modeling approach can be applied to many systems of interest such as acidic damage to limestone, mass transfer of contaminants in concrete and other porous building materials, and modeling pollutant transport in subsurface moisture zones.

Inhibition of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (MPTP) Opening in Ischemia-Damaged Mitochondria

PubMed Central

Chen, Qun; Xu, Haishan; Xu, Aijun; Ross, Thomas; Bowler, Elizabeth; Hu, Ying; Lesnefsky, Edward J.

2015-01-01

Background Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. Methods Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. Results CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with increasing HA14-1concentrations increased calcium-stimulated MPTP opening, supporting that functional inhibition of bcl-2 during simulated reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased the permeability of the outer membrane in the absence of exogenous calcium, indicating that bcl-2 inhibition favors MOMP when calcium is low. Conclusions The depletion and functional inhibition of bcl-2 contributes to cardiac injury by increasing susceptibility to MPTP opening in high calcium environments and MOMP in the absence of calcium overload. Thus, ischemia-damaged mitochondria with decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and MOMP later in reperfusion when cytosolic calcium has normalized. PMID:25756500

Analysis of Ricefield Land Damage in Denpasar City, Bali, Indonesia

NASA Astrophysics Data System (ADS)

Suyarto, R.; Wiyanti; Dibia, I. N.

2018-02-01

Soil as a natural resource, living area, environmental media, and factors of production including biomass production that supports human life and other living beings must be preserved, on the other hand, uncontrolled biomass production activities can cause soil damage, ultimately can threaten the survival of humans and other living things. Therefore, in order to control soil damage, first must inventories the soil condition data and its damage which then visualised in soil damage potential and soil damage status. The activities of the study are the preparation of a map of the initial soil conditions and the delineation of potentially land degradation distribution. Mapping results are used as work maps for verification on the field to take soil samples and create soil damage status. In general, Denpasar City have soil damage potential at very low, low until medium rate. Soil damage status in Denpasar City generally is low damage of bulk volume, total porosity, soil permeability and electrolyte conductivity which beyond limitation thresholds.

Effects of marine actinomycete on the removal of a toxicity alga Phaeocystis globose in eutrophication waters.

PubMed

Zhang, Huajun; Zhang, Su; Peng, Yun; Li, Yi; Chen, Zhangran; Xu, Hong; Yu, Zhiming; Zheng, Wei; Zheng, Tianling

2015-01-01

Phaeocystis globosa blooms in eutrophication waters can cause severely damage in marine ecosystem and consequently influence human activities. This study investigated the effect and role of an algicidal actinomycete (Streptomyces sp. JS01) on the elimination process of P. globosa. JS01 supernatant could alter algal cell membrane permeability in 4 h when analyzed with flow cytometry. Reactive oxygen species (ROS) levels were 7.2 times higher than that at 0 h following exposure to JS01 supernatant for 8 h, which indicated that algal cells suffered from oxidative damage. The Fv/Fm value which could reflect photosystem II (PS II) electron flow status also decreased. Real-time PCR showed that the expression of the photosynthesis related genes psbA and rbcS were suppressed by JS01 supernatant, which might induce damage to PS II. Our results demonstrated that JS01 supernatant can change algal membrane permeability in a short time and then affect photosynthesis process, which might block the PS II electron transport chain to produce excessive ROS. This experiment demonstrated that Streptomyces sp. JS01 could eliminate harmful algae in marine waters efficiently and may be function as a harmful algal bloom controller material.

Effects of marine actinomycete on the removal of a toxicity alga Phaeocystis globose in eutrophication waters

PubMed Central

Zhang, Huajun; Zhang, Su; Peng, Yun; Li, Yi; Chen, Zhangran; Xu, Hong; Yu, Zhiming; Zheng, Wei; Zheng, Tianling

2015-01-01

Phaeocystis globosa blooms in eutrophication waters can cause severely damage in marine ecosystem and consequently influence human activities. This study investigated the effect and role of an algicidal actinomycete (Streptomyces sp. JS01) on the elimination process of P. globosa. JS01 supernatant could alter algal cell membrane permeability in 4 h when analyzed with flow cytometry. Reactive oxygen species (ROS) levels were 7.2 times higher than that at 0 h following exposure to JS01 supernatant for 8 h, which indicated that algal cells suffered from oxidative damage. The Fv/Fm value which could reflect photosystem II (PS II) electron flow status also decreased. Real-time PCR showed that the expression of the photosynthesis related genes psbA and rbcS were suppressed by JS01 supernatant, which might induce damage to PS II. Our results demonstrated that JS01 supernatant can change algal membrane permeability in a short time and then affect photosynthesis process, which might block the PS II electron transport chain to produce excessive ROS. This experiment demonstrated that Streptomyces sp. JS01 could eliminate harmful algae in marine waters efficiently and may be function as a harmful algal bloom controller material. PMID:26042109

Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

PubMed

Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

2017-09-01

This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

Continuous Record of Permeability inside the Wenchuan Earthquake Fault Zone

NASA Astrophysics Data System (ADS)

Xue, Lian; Li, Haibing; Brodsky, Emily

2013-04-01

Faults are complex hydrogeological structures which include a highly permeable damage zone with fracture-dominated permeability. Since fractures are generated by earthquakes, we would expect that in the aftermath of a large earthquake, the permeability would be transiently high in a fault zone. Over time, the permeability may recover due to a combination of chemical and mechanical processes. However, the in situ fault zone hydrological properties are difficult to measure and have never been directly constrained on a fault zone immediately after a large earthquake. In this work, we use water level response to solid Earth tides to constrain the hydraulic properties inside the Wenchuan Earthquake Fault Zone. The transmissivity and storage determine the phase and amplitude response of the water level to the tidal loading. By measuring phase and amplitude response, we can constrain the average hydraulic properties of the damage zone at 800-1200 m below the surface (~200-600 m from the principal slip zone). We use Markov chain Monte Carlo methods to evaluate the phase and amplitude responses and the corresponding errors for the largest semidiurnal Earth tide M2 in the time domain. The average phase lag is ~ 30o, and the average amplitude response is 6×10-7 strain/m. Assuming an isotropic, homogenous and laterally extensive aquifer, the average storage coefficient S is 2×10-4 and the average transmissivity T is 6×10-7 m2 using the measured phase and the amplitude response. Calculation for the hydraulic diffusivity D with D=T/S, yields the reported value of D is 3×10-3 m2/s, which is two orders of magnitude larger than pump test values on the Chelungpu Fault which is the site of the Mw 7.6 Chi-Chi earthquake. If the value is representative of the fault zone, then this means the hydrology processes should have an effect on the earthquake rupture process. This measurement is done through continuous monitoring and we could track the evolution for hydraulic properties after Wenchuan earthquake. We observed the permeability decreases 35% per year. For the purpose of comparison, we convert the permeability measurements to into equivalent seismic velocity. The possible range of seismic wave velocity increase is 0.03%~ 0.8% per year. Our results are comparable to the results of the previous hydraulic and seismic studies after earthquakes. This temporal decrease of permeability may reflect the healing process after Wenchuan Earthquake.

Continuous Record of Permeability inside the Wenchuan Earthquake Fault Zone

NASA Astrophysics Data System (ADS)

Xue, L.; Li, H.; Brodsky, E. E.; Wang, H.; Pei, J.

2012-12-01

Faults are complex hydrogeological structures which include a highly permeable damage zone with fracture-dominated permeability. Since fractures are generated by earthquakes, we would expect that in the aftermath of a large earthquake, the permeability would be transiently high in a fault zone. Over time, the permeability may recover due to a combination of chemical and mechanical processes. However, the in situ fault zone hydrological properties are difficult to measure and have never been directly constrained on a fault zone immediately after a large earthquake. In this work, we use water level response to solid Earth tides to constrain the hydraulic properties inside the Wenchuan Earthquake Fault Zone. The transmissivity and storage determine the phase and amplitude response of the water level to the tidal loading. By measuring phase and amplitude response, we can constrain the average hydraulic properties of the damage zone at 800-1200 m below the surface (˜200-600 m from the principal slip zone). We use Markov chain Monte Carlo methods to evaluate the phase and amplitude responses and the corresponding errors for the largest semidiurnal Earth tide M2 in the time domain. The average phase lag is ˜30°, and the average amplitude response is 6×10-7 strain/m. Assuming an isotropic, homogenous and laterally extensive aquifer, the average storage coefficient S is 2×10-4 and the average transmissivity T is 6×10-7 m2 using the measured phase and the amplitude response. Calculation for the hydraulic diffusivity D with D=T/S, yields the reported value of D is 3×10-3 m2/s, which is two orders of magnitude larger than pump test values on the Chelungpu Fault which is the site of the Mw 7.6 Chi-Chi earthquake. If the value is representative of the fault zone, then this means the hydrology processes should have an effect on the earthquake rupture process. This measurement is done through continuous monitoring and we could track the evolution for hydraulic properties after Wenchuan earthquake. We observed the permeability decreases 35% per year. For the purpose of comparison, we convert the permeability measurements to into equivalent seismic velocity. The possible range of seismic wave velocity increase is 0.03%~ 0.8% per year. Our results are comparable to the results of the previous hydraulic and seismic studies after earthquakes. This temporal decrease of permeability may reflect the healing process after Wenchuan Earthquake.

Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.

PubMed

Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua

2006-10-18

Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of tonoplast by treatment with monocarboxylates such as acetic acid may be the main reason for the greening of garlic.

Internal architecture, permeability structure, and hydrologic significance of contrasting fault-zone types

NASA Astrophysics Data System (ADS)

Rawling, Geoffrey C.; Goodwin, Laurel B.; Wilson, John L.

2001-01-01

The Sand Hill fault is a steeply dipping, large-displacement normal fault that cuts poorly lithified Tertiary sediments of the Albuquerque basin, New Mexico, United States. The fault zone does not contain macroscopic fractures; the basic structural element is the deformation band. The fault core is composed of foliated clay flanked by structurally and lithologically heterogeneous mixed zones, in turn flanked by damage zones. Structures present within these fault-zone architectural elements are different from those in brittle faults formed in lithified sedimentary and crystalline rocks that do contain fractures. These differences are reflected in the permeability structure of the Sand Hill fault. Equivalent permeability calculations indicate that large-displacement faults in poorly lithified sediments have little potential to act as vertical-flow conduits and have a much greater effect on horizontal flow than faults with fractures.

Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, M.J.; Adams, J.; Gu, X.A.

1990-10-01

We examined the local hemodynamic response of intestinal loops during acute necrotizing enterocolitis (NEC) in anesthetized rabbits. NEC was induced in ileal loops by transmural injection of a solution containing casein (10 mg/ml) and calcium gluconate (50 mg/ml) acidified to pH 4.0 with propionic or acetic acid. Control loops received casein only (pH 5.0). Mucosal damage was quantified by the blood-to-lumen movement of (51Cr)EDTA, fluid shifts into the lumen, and histology. Mean arterial pressure and loop blood flow were steady over the 3-hr period, loop fluid volume decreased, and there was no evidence of necrosis or epithelial damage. In loopsmore » receiving acidified casein and calcium gluconate, there was an immediate dramatic increase in loop blood flow that returned to baseline by 50 min. In addition, loop fluid volume was dramatically increased, necrosis was noted in the form of blunting and loss of villi, and sevenfold increase in (51Cr)EDTA permeability was evident. Administration of CV 1808 (30 mg/kg/hr), a selective adenosine2 agonist, which maintained and elevated loop blood flow throughout the 3 hr protocol, failed to alter the changes in loop fluid volume or prevent necrosis. Histamine levels in loop fluid levels were significantly elevated 20-30 min after NEC induction when compared to saline controls, indicating an early activation of mucosal defenses with this luminal insult. Thus, this model of NEC is characterized by a transient, acute hyperemia, increased intestinal permeability, and histamine release. As mucosal damage was independent of ischemia and could not be prevented by vasodilatory therapy, this model supports the clinical findings that NEC is correlated with luminal factors related to feeding and independent of cardiovascular stress.« less

Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilson, Christy M.; Gaber, M. Waleed; Sabek, Omaima M.

2009-07-01

Purpose: In this article, we investigate the role of tumor necrosis factor-alpha (TNF) in the initiation of acute damage to the blood-brain barrier (BBB) and brain tissue following radiotherapy (RT) for CNS tumors. Methods and Materials: Intravital microscopy and a closed cranial window technique were used to measure quantitatively BBB permeability to FITC-dextran 4.4-kDa molecules, leukocyte adhesion (Rhodamine-6G) and vessel diameters before and after 20-Gy cranial radiation with and without treatment with anti-TNF. Immunohistochemistry was used to quantify astrogliosis post-RT and immunofluorescence was used to visualize protein expression of TNF and ICAM-1 post-RT. Recombinant TNF (rTNF) was used to elucidatemore » the role of TNF in leukocyte adhesion and vessel diameter. Results: Mice treated with anti-TNF showed significantly lower permeability and leukocyte adhesion at 24 and 48 h post-RT vs. RT-only animals. We observed a significant decrease in arteriole diameters at 48 h post-RT that was inhibited in TNF-treated animals. We also saw a significant increase in activated astrocytes following RT that was significantly lower in the anti-TNF-treated group. In addition, immunofluorescence showed protein expression of TNF and ICAM-1 in the cerebral cortex that was inhibited with anti-TNF treatment. Finally, administration of rTNF induced a decrease in arteriole diameter and a significant increase in leukocyte adhesion in venules and arterioles. Conclusions: TNF plays a significant role in acute changes in BBB permeability, leukocyte adhesion, arteriole diameter, and astrocyte activation following cranial radiation. Treatment with anti-TNF protects the brain's microvascular network from the acute damage following RT.« less

Relationship between lesion formation and permeability of rat gastric mucosa to H+ and other cations.

PubMed Central

Bunce, K. T.; McCarthy, J. J.; Spraggs, C. F.; Stables, R.

1982-01-01

The relationship between lesion formation and ionic permeability has been investigated in rat gastric mucosa in vivo. Changes in these parameters were measured in the mucosa treated topically with prostaglandins E2 and A2 and/or aspirin. Particular attention was paid to the net flux of H+ ions across the gastric mucosa. The effect of aspirin concentrations of 5 mM, 20 mM and '40 mM' (the latter, a suspension in a saturated solution) was investigated. Aspirin concentrations of 20 mM and '40 mM' produced a marked increase in lesion formation and increased the net mucosal to serosal flux of H+ ions. Aspirin 5 mM produced a significant increase in lesion formation but did not cause a significant change in net H+ ion flux. This result suggests that aspirin can have a direct irritant effect on the gastric mucosa and that the back diffusion of H+ ions is not a pre-requisite for the development of overt mucosal ulceration. The effect of topically applied prostaglandin E2 (PGE2) on aspirin-induced gastric mucosal damage was investigated. Concentrations of PGE2 of 10(-5) M and 10(-4) M ameliorated aspirin-induced damage, but these changes were not necessarily accompanied by a significant reduction in net H+ ion flux. Again, this result is not consistent with a direct relationship between lesion formation and mucosal permeability to H+ ions. Since PGA2 did not ameliorate aspirin-induced mucosal damage, the protective effect of PGE2 could not be attributed to its conversion to PGA2 in the acidic environment of the gastric lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6964662

Localized Versus Distributed Deformation as a Control on the Evolution of Permeability in Anhydrite Rocks

NASA Astrophysics Data System (ADS)

Collettini, C.; de Paola, N.; Faulkner, D.

2007-12-01

We have taken an experimental approach to understand and quantify the deformation processes and fluid flow within anhydrite-bearing fault damage zones during the seismic cycle. Triaxial loading tests have been performed on borehole samples of anhydrites at room temperature, 100 MPa confining pressure (Pc), and range of pore fluid pressures (Pf). Permeability and porosity development was continuously measured throughout the deformation experiments. The tests were conducted on samples with different grain sizes (10 microns to 1 mm) that were cored in different directions relative to the macroscopic foliation. Static permeability measurements have been carried out to determine the permeability anisotropy and sensitivity of the permeability on the effective pressure (Pc - Pf). Our results show that the brittle-ductile transition occurs for effective pressures (Pe) between 20 to 40 MPa and is almost independent of fabric orientation and grain size. Brittle failure is localized along discrete fractures and is always associated with a sudden stress drop. Conversely, ductile failure occurs by distributed deformation along cataclastic bands. In this case no stress drop is observed. Static permeability measurements show increasing values of permeability for decreasing values of Pe, (k = 10E-20 - 10E-22 m2). During single cycle loading tests, the evolution of the permeability is controlled by the failure mode: permeability begins to increase significantly at 40% and 80% of the max load for samples displaying brittle and ductile behaviour, respectively. The permeability values, immediately prior to failure, are about three orders of magnitude higher than the initial values. Multiple cycling tests, within the ductile field, show that permeability starts increasing at only 40% and 30% of the max load during the second and third loading cycle, respectively. Our results show that the history of deformation and the mode of deformation can control the evolution of the permeability, and that they are more significant than other factors such as fabric and grain size. In natural environments, fluid pressure fluctuations, such as might be experienced during the seismic cycle, can promote a switch from localized (brittle behaviour) to more distributed (ductile behaviour) deformation, leading to complex permeability patterns.

Fracture properties from tight reservoir outcrop analogues with application to geothermal exploration

NASA Astrophysics Data System (ADS)

Philipp, Sonja L.; Reyer, Dorothea; Afsar, Filiz; Bauer, Johanna F.; Meier, Silke; Reinecker, John

2015-04-01

In geothermal reservoirs, similar to other tight reservoirs, fluid flow may be intensely affected by fracture systems, in particular those associated with fault zones. When active (slipping) the fault core, that is, the inner part of a fault zone, which commonly consists of breccia or gouge, can suddenly develop high permeability. Fault cores of inactive fault zones, however, may have low permeabilities and even act as flow barriers. In the outer part of a fault zone, the damage zone, permeability depends mainly on the fracture properties, that is, the geometry (orientation, aperture, density, connectivity, etc.) of the fault-associated fracture system. Mineral vein networks in damage zones of deeply eroded fault zones in palaeogeothermal fields demonstrate their permeability. In geothermal exploration, particularly for hydrothermal reservoirs, the orientation of fault zones in relation to the current stress field as well as their internal structure, in particular the properties of the associated fracture system, must be known as accurately as possible for wellpath planning and reservoir engineering. Here we present results of detailed field studies and numerical models of fault zones and associated fracture systems in palaeogeo¬thermal fields and host rocks for geothermal reservoirs from various stratigraphies, lithologies and tectonic settings: (1) 74 fault zones in three coastal sections of Upper Triassic and Lower Jurassic age (mudstones and limestone-marl alternations) in the Bristol Channel Basin, UK. (2) 58 fault zones in 22 outcrops from Upper Carboniferous to Upper Cretaceous in the Northwest German Basin (siliciclastic, carbonate and volcanic rocks); and (3) 16 fault zones in 9 outcrops in Lower Permian to Middle Triassic (mainly sandstone and limestone) in the Upper Rhine Graben shoulders. Whereas (1) represent palaeogeothermal fields with mineral veins, (2) and (3) are outcrop analogues of reservoir horizons from geothermal exploration. In the study areas of palaeo¬geothermal fields in the Bristol Channel (1), all mineral veins, most of which are extension fractures, are of calcite. They are clearly associated with the faults and indicate that geothermal water was transported along the then-active faults into the host rocks with evidence of injection as hydrofractures. Layers with contrasting mechanical properties (in particular, stiffnesses), however, acted as stress barriers and lead to fracture arrest. Along some faults, veins propagated through the barriers along faults to shallower levels. In the Northwest German Basin (2) there are pronounced differences between normal-fault zones in carbonate and clastic rocks. Only in carbonate rocks clear damage zones occur, characterized by increased fracture frequencies and high amounts of fractures with large apertures. On the Upper Rhine Graben shoulders (3) damage zones in Triassic Muschelkalk limestones are well developed; fault cores are narrow and comprise breccia, clay smear, host rock lenses and mineralization. A large fault zone in Triassic Bunter sandstone shows a clearly developed fault core with fault gouge, slip zones, deformation bands and host rock lenses, a transition zone with mostly disturbed layering and highest fracture frequency, and a damage zone. The latter damage zone is compared to the damage zone of a large Bunter sandstone fault zone currently explored for geothermal energy production. The numerical models focus on stress field development, fracture propagation and associated permeability changes. These studies contribute to the understanding of the hydromechanical behaviour of fault zones and related fluid transport in fractured reservoirs complementing predictions based on geophysical measurements. Eventually we aim at classifying and quantifying fracture system properties in fault zones to improve exploration and exploitation of geothermal reservoirs. Acknowledgements The authors appreciate the support of 'Niedersächsisches Ministerium für Wissen¬schaft und Kultur' and 'Baker Hughes' within the gebo research project (http://www.gebo-nds.de), the Bundesministerium für Umwelt, Naturschutz, Bau und Reaktorsicherheit (BMU; FKZ: 0325302, AuGE) and the Deutsche Forschungsgemeinschaft. GeoEnergy GmbH, Karlsruhe, is thanked for explorational data.

Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes

PubMed Central

Tseng, Chia-Yi; Chang, Jing-Fen; Wang, Jhih-Syuan; Chang, Yu-Jung; Gordon, Marion K.; Chao, Ming-Wei

2015-01-01

Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione. PMID:26148005

Regulation of intestinal permeability: The role of proteases

PubMed Central

Van Spaendonk, Hanne; Ceuleers, Hannah; Witters, Leonie; Patteet, Eveline; Joossens, Jurgen; Augustyns, Koen; Lambeir, Anne-Marie; De Meester, Ingrid; De Man, Joris G; De Winter, Benedicte Y

2017-01-01

The gastrointestinal barrier is - with approximately 400 m2 - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases. PMID:28405139

Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition.

PubMed

Petit, P X; Goubern, M; Diolez, P; Susin, S A; Zamzami, N; Kroemer, G

1998-04-10

Upon induction of permeability transition with different agents (Ca2+, tert-butyl hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a disruption of outer membrane integrity leading to the release of cytochrome c and apoptosis-inducing factor (AIF), two proteins which are involved in programmed cell death (apoptosis). Chelation of Ca2+ shortly (within 2 min) after its addition to isolated mitochondria reestablished the mitochondrial transmembrane potential (deltapsi(m)), prevented induction of large amplitude swelling and release of both cytochrome c and AIF. In contrast, late Ca2+ chelation (10 min after addition of Ca2+) failed to affect these parameters. Cytochrome c appears to be released through a mechanically damaged outer mitochondrial membrane rather than via a specific release mechanism. These findings clarify the mechanisms through which irreversible permeability transition occurs with subsequent large amplitude swelling culminating in the release of intermembrane proteins from mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7-10 and Q. Rev. Biophys. 29 (1996) 169-2021 linking permeability transition to activation of the apoptogenic catabolic enzymes.

Fluorescein permeability and electrical resistance of human skin during low frequency ultrasound application.

PubMed

Cancel, Limary M; Tarbell, John M; Ben-Jebria, Abdellaziz

2004-09-01

Transdermal drug delivery offers an alternative to injections and oral medication but is limited by the low skin permeability of most drugs. The use of low-frequency ultrasound over long periods of time, typically over an hour, has been shown to enhance skin permeability, a phenomenon referred to as sonophoresis. In this study, we investigated the effects of short time sonication of human skin at 20 kHz and at variable intensities and duty cycles on the dynamics of fluorescein transport across the skin (permeability) as well as the changes in the skin's structural integrity (electrical resistance). We found that a short application of ultrasound enhanced the transport of fluorescein across human skin by a factor in the range of 2-9 for full thickness skin samples and by a factor in the range of 2-28 000 for heat-stripped stratum corneum samples (however, samples with very high (10(3)) enhancement were likely to have been damaged by ultrasound). The electrical resistance of the skin decreased by an average of 20% for full thickness samples and 58% for stratum corneum samples. Increasing the duty cycle from 10 to 60% caused a significant increase in permeability enhancement from 2.3 to 9.1, and an increase in intensity from 8 to 23 mW cm(-2) induced a significant increase in permeability enhancement from 2 to 7.4, indicating a clear dependence of the permeability on both duty cycle and intensity. The increase in solute flux upon ultrasound exposure was immediate, demonstrating for the first time the fast response dynamics of sonophoretic enhancement. In addition, a quantitative analysis of the thermal and convective dispersion effects associated with ultrasound application showed that each contributes significantly to the overall permeability enhancement observed.

Response of plasma membrane H+-ATPase in rice (Oryza sativa) seedlings to simulated acid rain.

PubMed

Liang, Chanjuan; Ge, Yuqing; Su, Lei; Bu, Jinjin

2015-01-01

Understanding the adaptation of plants to acid rain is important to find feasible approaches to alleviate such damage to plants. We studied effects of acid rain on plasma membrane H(+)-ATPase activity and transcription, intracellular H(+), membrane permeability, photosynthetic efficiency, and relative growth rate during stress and recovery periods. Simulated acid rain at pH 5.5 did not affect plasma membrane H(+)-ATPase activity, intracellular H(+), membrane permeability, photosynthetic efficiency, and relative growth rate. Plasma membrane H(+)-ATPase activity and transcription in leaves treated with acid rain at pH 3.5 was increased to maintain ion homeostasis by transporting excessive H(+) out of cells. Then intracellular H(+) was close to the control after a 5-day recovery, alleviating damage on membrane and sustaining photosynthetic efficiency and growth. Simulated acid rain at pH 2.5 inhibited plasma membrane H(+)-ATPase activity by decreasing the expression of H(+)-ATPase at transcription level, resulting in membrane damage and abnormal intracellular H(+), and reduction in photosynthetic efficiency and relative growth rate. After a 5-day recovery, all parameters in leaves treated with pH 2.5 acid rain show alleviated damage, implying that the increased plasma membrane H(+)-ATPase activity and its high expression were involved in repairing process in acid rain-stressed plants. Our study suggests that plasma membrane H(+)-ATPase can play a role in adaptation to acid rain for rice seedlings.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models.

PubMed

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.

Muscle enzyme and fiber type-specific sarcomere protein increases in serum after inertial concentric-eccentric exercise.

PubMed

Carmona, G; Guerrero, M; Cussó, R; Padullés, J M; Moras, G; Lloret, M; Bedini, J L; Cadefau, J A

2015-12-01

Muscle damage induced by inertial exercise performed on a flywheel device was assessed through the serum evolution of muscle enzymes, interleukin 6, and fiber type-specific sarcomere proteins such as fast myosin (FM) and slow myosin (SM). We hypothesized that a model of muscle damage could be constructed by measuring the evolution of serum concentration of muscle proteins following inertial exercise, according to their molecular weight and the fiber compartment in which they are located. Moreover, by measuring FM and SM, the type of fibers that are affected could be assessed. Serum profiles were registered before and 24, 48, and 144 h after exercise in 10 healthy and recreationally active young men. Creatine kinase (CK) and CK-myocardial band isoenzyme increased in serum early (24 h) and returned to baseline values after 48 h. FM increased in serum late (48 h) and remained elevated 144 h post-exercise. The increase in serum muscle enzymes suggests increased membrane permeability of both fast and slow fibers, and the increase in FM reveals sarcomere disruption as well as increased membrane permeability of fast fibers. Consequently, FM could be adopted as a fiber type-specific biomarker of muscle damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Boldine Prevents Renal Alterations in Diabetic Rats

PubMed Central

Hernández-Salinas, Romina; Vielma, Alejandra Z.; Arismendi, Marlene N.; Boric, Mauricio P.; Sáez, Juan C.; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects. PMID:24416726

Boldine prevents renal alterations in diabetic rats.

PubMed

Hernández-Salinas, Romina; Vielma, Alejandra Z; Arismendi, Marlene N; Boric, Mauricio P; Sáez, Juan C; Velarde, Victoria

2013-01-01

Diabetic nephropathy alters both structure and function of the kidney. These alterations are associated with increased levels of reactive oxygen species, matrix proteins, and proinflammatory molecules. Inflammation decreases gap junctional communication and increases hemichannel activity leading to increased membrane permeability and altering tissue homeostasis. Since current treatments for diabetic nephropathy do not prevent renal damage, we postulated an alternative treatment with boldine, an alkaloid obtained from boldo with antioxidant, anti-inflammatory, and hypoglycemic effects. Streptozotocin-induced diabetic and control rats were treated or not treated with boldine (50 mg/Kg/day) for ten weeks. In addition, mesangial cells were cultured under control conditions or in high glucose concentration plus proinflammatory cytokines, with or without boldine (100 µmol/L). Boldine treatment in diabetic animals prevented the increase in glycemia, blood pressure, renal thiobarbituric acid reactive substances and the urinary protein/creatinine ratio. Boldine also reduced alterations in matrix proteins and markers of renal damage. In mesangial cells, boldine prevented the increase in oxidative stress, the decrease in gap junctional communication, and the increase in cell permeability due to connexin hemichannel activity induced by high glucose and proinflammatory cytokines but did not block gap junction channels. Thus boldine prevented both renal and cellular alterations and could be useful for preventing tissue damage in diabetic subjects.

The formation of inflammatory demyelinated lesions in cerebral white matter

PubMed Central

Maggi, Pietro; Cummings Macri, Sheila M.; Gaitán, María I.; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L.; Ellis, Mary; Wu, Tianxia; Silva, Afonso C.; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S.

2016-01-01

Objective Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. Methods At 7 tesla MRI, T1 maps, proton density and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain-barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. Results On average, BBB permeability increased 3.5 fold (p<0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, though permeability within the foci, but not outside, increased in the weeks before the animals died (p<0.0001). Interpretation This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. PMID:25088017

The formation of inflammatory demyelinated lesions in cerebral white matter.

PubMed

Maggi, Pietro; Macri, Sheila M Cummings; Gaitán, María I; Leibovitch, Emily; Wholer, Jillian E; Knight, Heather L; Ellis, Mary; Wu, Tianxia; Silva, Afonso C; Massacesi, Luca; Jacobson, Steven; Westmoreland, Susan; Reich, Daniel S

2014-10-01

Vascular permeability and inflammatory demyelination are intimately linked in the brain, but what is their temporal relationship? We aimed to determine the radiological correlates of the earliest tissue changes accompanying demyelination in a primate model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in the common marmoset. By 7T magnetic resonance imaging (MRI), T1 maps, proton density, and T2-weighted images were acquired before and after EAE induction in 5 marmosets (every other week before lesions appeared, weekly thereafter). From scans before and after intravenous injection of contrast material, we measured the evolution of lesional blood-brain barrier (BBB) permeability, comparing in vivo MRI to postmortem tissue examination. On average, BBB permeability increased 3.5-fold (p < 0.0001) over the 4 weeks prior to lesion appearance. Permeability gradually decreased after lesion appearance, with attendant changes in the distribution of inflammatory cells (predominantly macrophages and microglia) and demyelination. On tissue analysis, we also identified small perivascular foci of microglia and T cells without blood-derived macrophages or demyelination. These foci had no visible MRI correlates, although permeability within the foci, but not outside, increased in the weeks before the animals died (p < 0.0001). This study provides compelling evidence that in marmoset EAE, which forms lesions strongly resembling those of MS, early changes in vascular permeability are associated with perivascular inflammatory cuffing and parenchymal microglial activation but precede the arrival of blood-derived monocytes that accompany demyelination. Prospective detection of transient permeability changes could afford an opportunity for early intervention to forestall tissue damage in newly forming lesions. © 2014 American Neurological Association.

Low intensity pulse ultrasound stimulate chondrocytes growth in a 3-D alginate scaffold through improved porosity and permeability.

PubMed

Guo, Gepu; Lu, Lu; Ji, Hongfei; Ma, Yong; Dong, Rui; Tu, Juan; Guo, Xiasheng; Qiu, Yuanyuan; Wu, Junru; Zhang, Dong

2015-04-01

A 3-D scaffold culture system has been used to promote in producing functional chondrocytes for repairing damaged cartilage. In the present study, the low intensity pulse ultrasound (LIPUS) (P(-)=0, 0.055, 0.085 and 0.11 MPa) was applied to improve the porosity and permeability of a 3-D alginate scaffold which was beneficial for the nutrition supply and metabolism during cell growth in 3-D alginate scaffold. The porosity and permeability of the scaffold was quantitatively analyzed based on scanning electron microscopy examination and fluorescence image observation. The results suggest that, for the scaffold exposed to LIPUS, its porosity and permeability could be significantly enhanced by the increasing LIPUS amplitude, which might be induced by the microstreaming shear stress generated by ultrasound-driven microbubble oscillations. Furthermore, the assessments of cell proliferation and collagen II expression confirmed that chondrocytes growth could be effectively promoted in 3-D alginate scaffolds treated by LIPUS, because of the improved scaffold porosity and permeability might benefit cell growth space and nutrition supply. It should also be noticed that appropriate LIPUS driving parameters should be adapted to achieve optimized chondrocytes culture effect in 3-D alginate scaffold. Copyright © 2014 Elsevier B.V. All rights reserved.

Stress Analysis and Permeability Testing of Cryogenic Composite Feed Line

NASA Technical Reports Server (NTRS)

Chu, Tsuchin Philip

1999-01-01

For the next generation Single-Stage-To-Orbit (SSTO) Reusable Launch Vehicle (RLV), the use of advanced composite materials is highly desirable and critical to the success of the mission. NASA Marshall Space Flight Center (MSFC) has been working with the aerospace industry for many years to develop and demonstrate the cryogenic composite propellant tanks and feed lines technologies. A 50.8-mm diameter composite feed line for the Clipper Graham (DCY.A) was developed and tested. The purpose of the program is to demonstrate the LH2 permeability, composite to composite and metal joints, as well as composite flange interface of the composite feed line. Stress analysis and permeability testing have been performed on this article. Recently, a larger composite feed line design is being investigated and developed at MSFC for potential use in future RLV. The diameter of the feed line is 203 mm and the overall length is approximately 2.2 meters. This one piece unlined feed line consists of three straight tubular sections joined by two 90 degree elbows. The material chosen is IM7/977-3 prepreg fabric. The lay-up pattern is [0/90, plus or minus 45]s and is built up to 18 plies to the flanges at both ends. A preliminary stress analysis has been conducted to identify potential critical stresses and to develop the finite element analysis (FEA) capability of composite feed lines. As expected, the critical stresses occurred at the rims of some flange holes and the onset of the tapered tubular sections. Further analysis is required to determine the loads, flange deflection, vibration, and combined maximum loads. Two permeability-testing apparatuses were also designed for both flat panel specimens and curved feed line sections after impact damage. A larger permeant gas exposed area is required to accurately determine the effect of impact damage on the permeability of the feed line materials. The flat panel tester was fabricated and assembled. Three test coupons were made of graphite/epoxy plain weave prepreg and unidirectional prepreg. The flow rate was calculated by measuring the change of manometer fluid height per unit time. The permeability of the coupons is then calculated according to Darcy's Law. The pressure increase due to the head rise in the manometer was not considered for the initial estimation. The result of the unidirectional composite coupon agreed with that obtained from the DC-XA feed line testing of a similar material. Further improvement on the design may be required to improve the accuracy and efficiency of permeability testing.

Experimental and Computational Studies of Coupled Geomechanical and Hydrologic Processes in Wellbore Systems (Invited)

NASA Astrophysics Data System (ADS)

Carey, J. W.; Mori, H.; Porter, M. L.; Lewis, K. C.; Kelkar, S.

2013-12-01

Potential leakage from wells is an important issue in the protection of groundwater resources, CO2 sequestration, and hydraulic fracturing. The first defense in all of these applications is a properly constructed well with adequate Portland cement that effectively isolates the subsurface. The chief threat for such wells is mechanical disruption of the cement, cement/steel, or cement/caprock interfaces. This can occur through wellbore operations that pressurize/depressurize the steel tubing or create temperature transients (e.g., injection, production, hydraulic fracturing, and mechanical testing) as well as reservoir-scale stresses (e.g., filling or depletion of the reservoir) and tectonic stresses (e.g., the mobility of salt). However, there is relatively limited information available on the hydrologic consequences of such processes. Toward this end, we discuss recent experiments and computational models of coupled geomechanical and hydrologic processes in wellbore systems. Triaxial coreflood experiments with tomography were conducted on synthetic wellbore systems including cement-steel, rock-cement and rock-cement-steel composites. The aim of the experiments was to induce stresses through application of axial loads in order to create defects within the cement or at the cement/steel or cement/rock interface. High injection fluid pressures (supercritical CO2 × brine) were applied to the base of the initially impermeable composites. Mechanical failure resulted in creation of permeability, which was measured as a function of time (allowing for the possibility of Portland cement to deform and modify permeability). In addition, fracture patterns were characterized using x-ray tomography. We used the computer code FEHM to study coupled hydrologic and mechanical processes in the near-wellbore environment. The wellbore model was developed as a wedge within a radially symmetric 3D volume. The grid elements consist of the steel casing, the casing-cement interface, the cement, the cement-rock interface, caprock, and reservoir rock. We used a model that is 1 m in radius, and extends 5 m along the wellbore. The model consisted of a lower storage aquifer, a caprock and an upper aquifer that received leaking fluids. We coupled flow and geomechanics using a shear-failure model that represents shear-induced damage and is similar to a Mohr-Coulomb slip mechanism. In this model, damage occurs for any excess shear stress with permeability enhancement a function of stress with a maximum magnitude set by the user. Stresses were induced by application of an elevated constant pressure within the injection reservoir representing a far-field injection process. The initial permeability of the cement was 1 mD and stress-enhanced permeability was limited to an increase by a factor of 10-100. The simulations show that shear-failure modes lead to enhanced permeability of the wellbore system. Continuing work will examine sensitivity of the results to mechanical properties and initial permeability distributions, the impact of relative permeability models, and the development of permeability-stress models including an aperture-opening tensile-failure model.

A linearized microstructural model for hydraulic conductivity evolution due to brittle damage: application to Hydraulic Fracturing treatments

NASA Astrophysics Data System (ADS)

Caramiello, G.; Montanino, A.; Della Vecchia, G., Sr.; Pandolfi, A., Sr.

2017-12-01

Among the features of geological structures, fractures and discontinuities play a dominant role, due to their significant influence on both the hydraulic and the mechanical behavior of the rock mass. Despite the current availability of fault and fracture mappings, the understanding of the influence of faults on fluid flow is nowadays not satisfactory, in particular when hydro-mechanical coupling is significant. In engineering technology fracture processes are often exploited. Hydraulic fracturing is one of the most important example. Hydraulic fracturing is a process characterized by the inception and propagation of fractures as a consequence of a hydraulic driven solicitation and it is used to improve the production and optimize well stimulation in low permeability reservoirs. Due to the coupling of several different phenomena (hydro-thermo-chemical coupling) there is not a reliable complete mathematical model able to simulate in a proper way the process. To design hydraulic fracturing treatments, it is necessary to predict the growth of fracture geometry as a function of treatment parameters. In this contribution we present a recently developed model of brittle damage of confined rock masses, with particular emphasis on the influence of mechanical damage on the evolution of porosity and permeability. The model is based on an explicit micromechanical construction of connected patterns of parallel equi-spaced cracks. A relevant feature of the model is that the fracture patterns are not arbitrary, but their inception, orientation and spacing follow from energetic consideration. The model, based on the Terzaghi effective stress concepts, has been then implemented into a coupled hydro-mechanical finite element code, where the linear momentum and the fluid mass balance equations are numerically solved via a staggered approach. The coupled code is used to simulate fracturing processes induced by an increase in pore pressure. The examples show the capability of the model in reproducing three-dimensional multiscale complex fracture patterns and permeability enhancement in the damaged porous medium. The numerical code, has been used to verify the influence of the distance between the different perforation slots as well of the wellbore-deviation from the minimum stress axis on the propagation of multiple.

Ca2+-Permeable AMPARs Mediate Glutamatergic Transmission and Excitotoxic Damage at the Hair Cell Ribbon Synapse.

PubMed

Sebe, Joy Y; Cho, Soyoun; Sheets, Lavinia; Rutherford, Mark A; von Gersdorff, Henrique; Raible, David W

2017-06-21

We report functional and structural evidence for GluA2-lacking Ca 2+ -permeable AMPARs (CP-AMPARs) at the mature hair cell ribbon synapse. By using the methodological advantages of three species (of either sex), we demonstrate that CP-AMPARs are present at the hair cell synapse in an evolutionarily conserved manner. Via a combination of in vivo electrophysiological and Ca 2+ imaging approaches in the larval zebrafish, we show that hair cell stimulation leads to robust Ca 2+ influx into afferent terminals. Prolonged application of AMPA caused loss of afferent terminal responsiveness, whereas blocking CP-AMPARs protects terminals from excitotoxic swelling. Immunohistochemical analysis of AMPAR subunits in mature rat cochlea show regions within synapses lacking the GluA2 subunit. Paired recordings from adult bullfrog auditory synapses demonstrate that CP-AMPARs mediate a major component of glutamatergic transmission. Together, our results support the importance of CP-AMPARs in mediating transmission at the hair cell ribbon synapse. Further, excess Ca 2+ entry via CP-AMPARs may underlie afferent terminal damage following excitotoxic challenge, suggesting that limiting Ca 2+ levels in the afferent terminal may protect against cochlear synaptopathy associated with hearing loss. SIGNIFICANCE STATEMENT A single incidence of noise overexposure causes damage at the hair cell synapse that later leads to neurodegeneration and exacerbates age-related hearing loss. A first step toward understanding cochlear neurodegeneration is to identify the cause of initial excitotoxic damage to the postsynaptic neuron. Using a combination of immunohistochemical, electrophysiological, and Ca 2+ imaging approaches in evolutionarily divergent species, we demonstrate that Ca 2+ -permeable AMPARs (CP-AMPARs) mediate glutamatergic transmission at the adult auditory hair cell synapse. Overexcitation of the terminal causes Ca 2+ accumulation and swelling that can be prevented by blocking CP-AMPARs. We demonstrate that CP-AMPARs mediate transmission at this first-order sensory synapse and that limiting Ca 2+ accumulation in the terminal may protect against hearing loss. Copyright © 2017 the authors 0270-6474/17/376162-14$15.00/0.

Effects of Aspirin on Gastroduodenal Permeability in Alcoholics and Controls

PubMed Central

Farhadi, Ashkan; Keshavarzian, Ali; Kwasny, Mary J.; Shaikh, Maliha; Fogg, Louis; Lau, Cynthia; Fields, Jeremy Z.; Forsyth, Christopher B.

2010-01-01

Alcohol and non-steroidal anti-inflammatory drugs (NSAIDS) are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier, and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents – measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5–12 h following ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1300 mg aspirin twice, 12 hours and 1 hour before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, p=0.003 and +2.25%, p = 0.011, respectively) but the magnitude of these increases were not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status). Our data show that alcoholics have greater gastroduodenal permeability than healthy controls. This difference was independent of the duration of any preceding period of sobriety, gender, smoking history, or illicit drug abuse. The injurious effects of alcohol on the gastroduodenal epithelial barrier are long lasting, persisting even after 7 days of sobriety. Although, acute aspirin and chronic alcohol each increase intestinal permeability in alcoholics, their effects appear to be additive rather than synergistic. PMID:20598487

Permeability of Concrete with Recycled Concrete Aggregate and Pozzolanic Materials under Stress

PubMed Central

Wang, Hailong; Sun, Xiaoyan; Wang, Junjie; Monteiro, Paulo J.M.

2016-01-01

The research reported herein studied the permeability of concrete containing recycled-concrete aggregate (RA), superfine phosphorous slag (PHS), and ground granulated blast-furnace slag (GGBS) with and without stress. Test results showed that the chloride diffusion coefficient of RA concrete (RAC) without external loads decreased with time, and the permeability of RAC is much lower than that of the reference concrete due to the on-going hydration and the pozzolanic reaction provided by the PHS and GGBS additives in the RAC mixture. The permeability of chloride under flexural load is much more sensitive than that under compressive load due to the differences in porosity and cracking pattern. At low compressive stress levels, the permeability of chloride decreased by the closing of pores and microcracks within RAC specimens. However, in a relatively short time the chloride diffusion coefficient and the chloride content increased rapidly with the increase of compressive stress when it exceeded a threshold stress level of approximate 35% of the ultimate compressive strength. Under flexural stress, the chloride transport capability increased with the increase of stress level and time. At high compressive and flexural stress levels, creep had a significant effect on the permeability of chloride in the RAC specimens due to the damage from the nucleation and propagation of microcracks over time. It is apparent that mortar cracking has more of a significant effect on the chloride transport in concrete than cracking in the interfacial transition zone (ITZ). PMID:28773376

Basalt fiber reinforced polymer composites: Processing and properties

NASA Astrophysics Data System (ADS)

Liu, Qiang

A high efficiency rig was designed and built for in-plane permeability measurement of fabric materials. A new data derivation procedure to acquire the flow fluid pattern in the experiment was developed. The measurement results of the in-plane permeability for basalt twill 31 fabric material showed that a high correlation exists between the two principal permeability values for this fabric at 35% fiber volume fraction. This may be the most important scientific contribution made in this thesis. The results from radial measurements corresponded quite well with those from Unidirectional (UD) measurements, which is a well-established technique. No significant differences in mechanical properties were found between basalt fabric reinforced polymer composites and glass composites reinforced by a fabric of similar weave pattern. Aging results indicate that the interfacial region in basalt composites may be more vulnerable to environmental damage than that in glass composites. However, the basalt/epoxy interface may have been more durable than the glass/epoxy interface in tension-tension fatigue because the basalt composites have significantly longer fatigue life. In this thesis, chapter I reviews the literature on fiber reinforced polymer composites, with concentration on permeability measurement, mechanical properties and durability. Chapter II discusses the design of the new rig for in-plane permeability measurement, the new derivation procedure for monitoring of the fluid flow pattern, and the permeability measurement results. Chapter III compares the mechanical properties and durability between basalt fiber and glass fiber reinforced polymer composites. Lastly, chapter IV gives some suggestions and recommendations for future work.

Permeability of Concrete with Recycled Concrete Aggregate and Pozzolanic Materials under Stress.

PubMed

Wang, Hailong; Sun, Xiaoyan; Wang, Junjie; Monteiro, Paulo J M

2016-03-30

The research reported herein studied the permeability of concrete containing recycled-concrete aggregate (RA), superfine phosphorous slag (PHS), and ground granulated blast-furnace slag (GGBS) with and without stress. Test results showed that the chloride diffusion coefficient of RA concrete (RAC) without external loads decreased with time, and the permeability of RAC is much lower than that of the reference concrete due to the on-going hydration and the pozzolanic reaction provided by the PHS and GGBS additives in the RAC mixture. The permeability of chloride under flexural load is much more sensitive than that under compressive load due to the differences in porosity and cracking pattern. At low compressive stress levels, the permeability of chloride decreased by the closing of pores and microcracks within RAC specimens. However, in a relatively short time the chloride diffusion coefficient and the chloride content increased rapidly with the increase of compressive stress when it exceeded a threshold stress level of approximate 35% of the ultimate compressive strength. Under flexural stress, the chloride transport capability increased with the increase of stress level and time. At high compressive and flexural stress levels, creep had a significant effect on the permeability of chloride in the RAC specimens due to the damage from the nucleation and propagation of microcracks over time. It is apparent that mortar cracking has more of a significant effect on the chloride transport in concrete than cracking in the interfacial transition zone (ITZ).

Effects of Salinity and Confining Pressure on Hydration-Induced Fracture Propagation and Permeability of Mancos Shale

NASA Astrophysics Data System (ADS)

Zhang, Shifeng; Sheng, James J.

2017-11-01

Low-salinity water imbibition was considered an enhanced recovery method in shale oil/gas reservoirs due to the resulting hydration-induced fractures, as observed at ambient conditions. To study the effect of confining pressure and salinity on hydration-induced fractures, time-elapsed computerized tomography (CT) was used to obtain cross-sectional images of shale cores. Based on the CT data of these cross-sectional images, cut faces parallel to the core axial in the middle of the core and 3D fracture images were also reconstructed. To study the effects of confining pressure and salinity on shale pore fluid flowing, shale permeability was measured with Nitrogen (N2), distilled water, 4% KCl solution, and 8% KCl solution. With confining pressures increased to 2 MPa or more, either in distilled water or in KCl solutions of different salinities, fractures were observed to close instead to propagate at the end of the tests. The intrinsic permeabilities of #1 and #2 Mancos shale cores were 60.0 and 7000 nD, respectively. When tested with distilled water, the permeability of #1 shale sample with 20.0 MPa confining pressure loaded, and #2 shale sample with 2.5 MPa confining pressure loaded, decreased to 0.45 and 15 nD, respectively. Using KCl can partly mitigate shale permeability degradation. Compared to 4% KCl, 8% KCl can decrease more permeability damage. From this point of view, high salinity KCl solution should be required for the water-based fracturing fluid.

Commercially Available Gas-Permeable Cell Culture Bags May Not Prevent Anoxia in Cultured or Shipped Islets

PubMed Central

Avgoustiniatos, E.S.; Hering, B.J.; Rozak, P.R.; Wilson, J.R.; Tempelman, L.A.; Balamurugan, A.N.; Welch, D.P.; Weegman, B.P.; Suszynski, T.M.; Papas, K.K.

2009-01-01

Prolonged anoxia has deleterious effects on islets. Gas-permeable cell culture devices can be used to minimize anoxia during islet culture and especially during shipment when elimination of gas-liquid interfaces is required to prevent the formation of damaging gas bubbles. Gas-permeable bags may have several drawbacks, such as propensity for puncture and contamination, difficult islet retrieval, and significantly lower oxygen permeability than silicone rubber membranes (SRM). We hypothesized that oxygen permeability of bags may be insufficient for islet oxygenation. We measured oxygen transmission rates through the membrane walls of three different types of commercially available bags and through SRM currently used for islet shipment. We found that the bag membranes have oxygen transmission rates per unit area about 100-fold lower than SRM. We solved the oxygen diffusion-reaction equation for 150-μm diameter islets seeded at 3000 islet equivalents per cm2, a density adequate to culture and ship an entire human or porcine islet preparation in a single gas-permeable device, predicting that about 40% of the islet volume would be anoxic at 22°C and about 70% would be anoxic at 37°C. Islets of larger size or islets accumulated during shipment would be even more anoxic. The model predicted no anoxia in islets similarly seeded in devices with SRM bottoms. We concluded that commercially available bags may not prevent anoxia during islet culture or shipment; devices with SRM bottoms are more suitable alternatives. PMID:18374080

Tight junction gene expression in gastrointestinal tract of dairy calves with coccidiosis and treated with glucagon-like peptide-2

USDA-ARS?s Scientific Manuscript database

Selective permeability of the intestinal epithelium and efficient nutrient absorption are important functions for proper growth and development of calves. Damage to the intestinal mucosa can give rise to harmful long-term health effects and reduce productivity of the mature animal. Tight junction pr...

THE PERMEABILITY OF RAT TRANSITIONAL EPITHELIUM

PubMed Central

Hicks, R. M.

1966-01-01

Permeability barriers must exist in transitional epithelium to prevent the free flow of water from underlying blood capillaries through the epithelium into the hypertonic urine, and such a barrier has now been demonstrated in isolated bladders. This barrier is passive in function and can be destroyed by damaging the luminal surface of the transitional epithelium with sodium hydroxide and 8 M urea solutions, by digesting it with trypsin, lecithinase C, and lecithinase D, or by treating it with lipid solvents such as Triton x 100 and saponin. From this it is concluded that the barrier depends on the integrity of lipoprotein cell membranes. The barrier function is also destroyed by sodium thioglycollate solutions, and electron microscope investigations show that sodium thioglycollate damages the thick asymmetric membrane which limits the luminal face of the superficial squamous cell. Cytochemical staining shows the epithelium to contain disulfide and thiol groups and to have a concentration of these groups at the luminal margin of the superficial cells. It thus appears that the permeability barrier also depends on the presence of disulfide bridges in the epithelium, and it is presumed that these links are located in keratin. Because of the effect of thioglycollates, both on the barrier function and on the morphology of the membrane, it is suggested that keratin may be incorporated in the thick barrier membrane. It is proposed that the cells lining the urinary bladder and ureters should be regarded as a keratinizing epitheluim. PMID:5901498

Time-dependent recovery of microcrack damage and seismic wave speeds in deformed limestone

NASA Astrophysics Data System (ADS)

Brantut, Nicolas

2015-12-01

Limestone samples were deformed up to 5% inelastic axial strain at an effective confining pressure Peff=50 MPa in the cataclastic flow regime and subsequently maintained under constant static stress conditions (either isostatic of triaxial) for extended periods of time while elastic wave speeds and permeability were continuously monitored. During deformation, both seismic wave speeds and permeability decrease with increasing strain, due to the growth of subvertical microcracks and inelastic porosity reduction. During the static hold period under water-saturated conditions, the seismic wave speeds recovered gradually, typically by around 5% (relative to their initial value) after 2 days, while permeability remained constant. The recovery in wave speed increases with increasing confining pressure but decreases with increasing applied differential stress. The recovery is markedly lower when the samples are saturated with an inert fluid as opposed to water. The evolution in wave speed is interpreted quantitatively in terms of microcrack density, which shows that the post-deformation recovery is associated with a decrease in effective microcrack length, typically of the order to 10% after 2 days. The proposed mechanism for the observed damage recovery is microcrack closure due to a combination of backsliding on wing cracks driven by time-dependent friction and closure due to pressure solution at contacts between propping particles or asperities and microcrack walls. The recovery rates observed in the experiments, and the proposed underlying mechanisms, are compatible with seismological observations of seismic wave speed recovery along faults following earthquakes.

Colonic responses to Lactobacillus farciminis treatment in trinitrobenzene sulphonic acid-induced colitis in rats.

PubMed

Lamine, F; Eutamène, H; Fioramonti, J; Buéno, L; Théodorou, V

2004-12-01

It has recently been shown that Lactobacillus farciminis treatment exerts an anti-inflammatory effect in trinitrobenzene sulphonic acid (TNBS)-induced colitis partly through a nitric oxide release by this strain. The aim of this study was to evaluate whether L. farciminis treatment shares also the general mechanisms of action involved in the beneficial effect of probiotics in the colonic inflammatory process. Rats received L. farciminis for 15 days before and 4 days after intracolonic administration of TNBS or vehicle. The following parameters were evaluated: macroscopic damage of colonic mucosa, myeloperoxidase activity, cytokine mucosal levels, bacterial profile in colonic content and mucosa, bacterial translocation and colonic paracellular permeability. In the absence of TNBS, L. farciminis treatment reduced colonic paracellular permeability and increased the IL-10 level in the colonic wall. TNBS administration induced colonic macroscopic damage, associated with an increase of myeloperoxidase activity, bacterial translocation, colonic paracellular permeability and IL-1beta mucosal level, and a decrease in IL-10 mucosal level. Moreover, the bacterial profile of colonic content and mucosa was modified. All these alterations were abolished or significantly reduced by L. farciminis treatment. As previously shown, L. farciminis treatment improves TNBS-induced colitis. This study indicates that, in addition to the nitric oxide released by this bacterial strain, the anti-inflammatory action of L. farciminis involves also normalization of colonic microflora, prevention of bacterial translocation, enhancement of barrier integrity and a decrease in the IL-1beta mucosal level.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

PubMed Central

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

Purpose The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Methods Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Results Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. Conclusion These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye. PMID:23386781

Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells.

PubMed

Lee, Chung Soo; Park, Se Young; Ko, Hyun Hee; Song, Jin Ho; Shin, Yong Kyoo; Han, Eun Sook

2005-01-01

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of trifluoperazine and W-7 on the MPP+-induced mitochondrial damage and cell death in undifferentiated PC12 cells. Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) at 0.5-1 microM significantly reduced the loss of cell viability in PC12 cells treated with 500 microM MPP+. Trifluoperazine and W-7 (0.5-1 microM) inhibited the nuclear damage, the loss of the mitochondrial transmembrane potential followed by cytochrome c release, and the elevation of intracellular Ca2+ levels due to MPP+ in PC12 cells and attenuated the formation of reactive oxygen species and the depletion of GSH. Calmodulin antagonists at 5-10 microM exhibited a cytotoxic effect on PC12 cells, and compounds at 10 microM did not attenuate cytotoxicity of MPP+. Calmodulin antagonists (0.5-1 microM) significantly reduced rotenone-induced mitochondrial damage and cell death, whereas they did not attenuate cell death and elevation of intracellular Ca2+ levels due to H2O2 or ionomycin. The results show that trifluoperazine and W-7 exhibit a differential inhibitory effect against cytotoxicity of MPP+ depending on concentration. Both compounds at the concentrations less than 5 microM may attenuate the MPP+-induced viability loss in PC12 cells by suppressing change in the mitochondrial membrane permeability and by lowering the intracellular Ca2+ levels.

Chronic Changes in the Articular Cartilage and Meniscus Following Traumatic Impact to the Lapine Knee

PubMed Central

Fischenich, Kristine M.; Button, Keith D.; Coatney, Garrett A.; Fajardo, Ryan S.; Leikert, Kevin M.; Haut, Roger C.; Haut Donahue, Tammy L.

2014-01-01

The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p<0.0001) compared to controls. Chronic meniscal damage was most prevalent in the medial central and medial posterior regions. Mechanical tests revealed an overall 19.4% increase in tibial plateau cartilage thickness (p=0.026), 34.8% increase in tibial plateau permeability (p=0.054), 40.8% increase in femoral condyle permeability (p=0.029), and 20.1% decrease in femoral condyle matrix modulus (p=0.012) in impacted joints compared to controls. Both the instantaneous and equilibrium moduli of the lateral and medial menisci were decreased compared to control (p<0.02). Histological analyses revealed significantly increased presence of fissures in the medial femur (p = 0.036). In both the meniscus and cartilage there was a significant decrease in GAG coverage for the impacted limbs. Based on these results it is clear that an unattended combined meniscal and ACL injury results in significant changes to the soft tissues in this experimental joint 12 weeks post injury. Such changes are consistent with a clinical description of mid to late stage PTOA of the knee. PMID:25523754

Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.

PubMed

Bjarnason, I; Smethurst, P; Clark, P; Menzies, I; Levi, J; Peters, T

1989-01-01

This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.

Fracture propagation and fluid transport in palaeogeothermal fields and man-made reservoirs in limestone

NASA Astrophysics Data System (ADS)

Philipp, S. L.; Reyer, D.; Meier, S.

2009-04-01

Geothermal reservoirs are rock units from which the internal heat can be extracted using water as a transport means in an economically efficient manner. In geothermal reservoirs in limestone (and similar in other rocks with low matrix permeability), fluid flow is largely, and may be almost entirely, controlled by the permeability of the fracture network. No flow, however, takes place along a particular fracture network unless the fractures are interconnected. For fluid flow to occur from one site to another there must be at least one interconnected cluster of fractures that links these sites (the percolation threshold must be reached). In order to generate permeability in man-made reservoirs, interconnected fracture systems are formed either by creating hydraulic fractures or by massive hydraulic stimulation of the existing fracture system in the host rock. For effective stimulation, the geometry of the fracture system and the mechanical properties of the host rock (particularly rock stiffnesses and strengths) must be known. Here we present results of a study of fracture systems in rocks that could be used to host man-made geothermal reservoirs: the Muschelkalk (Middle Triassic) limestones in Germany. Studies of fracture systems in exposed palaeogeothermal fields can also help understand the permeability development in stimulated reservoirs. We therefore present data on the infrastructures of extinct fracture-controlled geothermal fields in fault zones in the Blue Lias (Lower Jurassic), Great Britain. In fault zones there are normally two main mechanical and hydrogeological units. The fault core, along which fault slip mostly occurs, consists mainly of breccia and other cataclastic rocks. The fault damage zone comprises numerous fractures of various sizes. During fault slip, the fault core may transport water (if its orientation is favourable to the hydraulic gradient in the area). In the damage zone, however, fluid transport through fracture networks depends particularly on the current local stress field. One reason for this is that fractures are sensitive to changes in the stress field and deform much more easily than circular pores. If the maximum horizontal compression is oriented perpendicular to the fault strike, its fractures (mainly in the damage zone) tend to be closed and lead less water than if the maximum horizontal compression is oriented parallel to the fault strike, in which case its fractures tend to open up and be favourable to fluid transport. In areas of potential geothermal reservoirs, fault zones must be studied, keeping in mind that the permeability structure of a fault zone depends partly on the mechanical units of the fault zone and partly on the local stress field. To explore stress fields affecting fracture propagation we have run numerical models using the finite-element and the boundary-element methods. We focus on the influence of changes in mechanical properties (particularly Young's modulus) between host rock layers in geothrmal reservoirs in limestone. The numerical models show that stresses commonly concentrate in stiff layers. Also, at the contacts between soft marl and stiffer limestone layers, the stress trajectories (directions of the principal stresses) may become rotated. Depending on the external loading conditions, certain layers may become stress barriers to fracture propagation. In a reservoir where most hydrofractures become stratabound (confined to individual layers), interconnected fracture systems are less likely to develop than in one with non-stratabound hydrofractures. Reservoirs with stratabound fractures may not reach the percolation threshold needed for significant permeability. We also used the field data to investigate the fracture-related permeability of fluid reservoirs in limestone with numerical models. We simulated different scenarios, in which potential fluid pathways were added successively (vertical extension fractures, inclined shear fractures and open layer contacts). Short and straight fluid pathways parallel to the flow direction lead to the highest permeabilities. The better the connectivity of the fracture system, the higher is the resulting permeability. Only in well-interconnected, continuous systems of fluid pathways there is a correlation between the apertures of the fractures and the permeability. Our results suggest that fluid transport along faults, and the propagation and aperture variation of hydrofractures, are important parameters in the permeability development of geothermal reservoirs. These studies provide a basis for models of fracture networks and fluid transport in future man-made reservoirs. We conclude that the likely permeability of a man-made geothermal reservoir can be inferred from field data, natural analogues, laboratory measurements, and numerical models.

The Fluid Flow Evolution During the Seismic Cycle Within Overpressured Fault Zones

NASA Astrophysics Data System (ADS)

de Paola, Nicola; Vanhunen, Jeroen; Collettini, Cristiano; Faulkner, Dan

2010-05-01

The integration of seismic reflection profiles with well-located earthquakes shows that the mainshocks of the 1997 Umbria-Marche seismic sequence (Mw < 6) nucleated at about 6 km depth, within the Triassic Evaporites, a 2 km thick sequence made of interbedded anhydrites and dolostones. Two boreholes, drilled northwest of the epicentral area, encountered CO2 fluid overpressures at about 0.8 of the lithostatic load, at about 4 km depth. It has been proposed that the time-space evolution of the 1997 aftershock sequence, was driven by the coseismic release of trapped high-pressure fluids (lv = 0.8), within the Triassic Evaporites. In order to understand whether CO2 fluid overpressure can be maintained up to the coseismic period, and trigger earthquake nucleation, we modelled fluid flow through a mature fault zone within the Triassic Evaporites. We assume that fluid flow within the fault zone occurs in accord with the Darcy's Law. Under this condition, a near lithostatic pore pressure gradient can develop, within the fault zone, when the upward transport of fluid along the fault zone exceeds the fluid loss in a horizontal direction. Our model's parameters are: a) Fault zone structure: model inputs have been obtained from large fault zone analogues derived from field observation. The architecture of large fault zones within the TE is given by a distinct fault core, up to few meters thick, of very fine-grained fault rocks (cataclasites and fault gouge), where most of the shear strain has been accommodated, surrounded by a geometrically complex and heterogeneous damage zone (up to few tens of meters wide). The damage zone is characterized by adjacent zones of heavily fractured rocks (dolostones) and foliated rocks displaying little fracturing (anhydrites). b) Fault zone permeability: field data suggests that the permeability of the fault core is relatively low due to the presence of fine grained fault rocks (k < 10E-18 m2). The permeability of the dolostones, within the damage zone, is likely to be high and controlled by mesoscale fracture patterns (k > 10E-17 m2). For the anhydrites, the permeability and porosity development was continuously measured prior and throughout triaxial loading tests, performed on borehole samples. The permeability of the anhydrites within the damage zone, due to the absence of mesoscale fracture patterns within Ca-sulphates layers, has been assumed to be as low as the values measured during our lab experiments (k = 10E-17 - 10E-20 m2). Our model results show that, during the seismic cycle, the lateral fluid flux, across the fault zone, is always lower than the vertical parallel fluid flux. Under these conditions fluid overpressure within the fault zone can be sustained up to the coseismic period when earthquake nucleation occurs. Our modelling shows that during extensional loading, overpressured fault zones within the Triassic Evaporites may develop and act as asperities, i.e. they are mechanically weaker than faults within the overlain carbonates at hydrostatic (lv = 0.4) pore fluid pressure conditions.

Controls on Permeability Evolution in Fractured-Sorbing Media

NASA Astrophysics Data System (ADS)

Elsworth, D.

2017-12-01

A critical component in the desire to recover energy and fuels from the subsurface, or to sequester energy-related and other wastes, is the ability to control properties that influence the transport and storage of mass, fluids and energy. In fractured media, permeabilities are strongly dependent on effective stresses. In turn, effective stresses (M) are mediated by changes in fluid pressures (H), compositions of the permeating fluids and permeated rocks (C) and changes in temperature (T) - and sometimes influenced by biological (B) processes. First we explore the role of specific complex THMC(B) interactions in mediating changes in permeability in response to a change in spherical stress. These include the roles of differential strains, induced within shales by changes in pressure (H), gas concentration (C) or temperature (T), in driving changes in permeability, in particular where the effects of sorption are pronounced. We show that the influence of such pressure-, sorption- and thermally-induced changes in damage and porosity are countered, by the first order resetting effects of creep that influence the crack distribution within the fractured aggregate. Second, we explore linkages where friction and instability control the response to changes in differential stress. Changes in permeability are controlled by styles of deformation - brittle versus ductile - with modes of deformation in turn mediated by mineralogy of both native and altered mineral constituents, the evolving scale of deformation and in the progress of deformation through the dynamic loading cycle.

Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

2014-11-01

Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

Permeability Development at Layer Interfaces in Bedded Rocksalt

NASA Astrophysics Data System (ADS)

Muhammad, N.; Spiers, C. J.; Peach, C. J.; De Bresser, J. H. P.; Liu, W.

2016-12-01

Solution mined salt caverns are of great interest for storage of fluids such as compressed air, natural gas or hydrogen fuel, and are expected to show excellent healing and sealing capacity. However, it is of utmost importance to be able to reliably quantify the permeability of salt cavern walls, so that potential loss of the stored asset may be assessed. Data on dilatancy, permeability and damage development are readily available for pure rocksalt undergoing deformation, but little is known about the permeability development at the bedding interfaces within layered salt under varying differential stresses. Layered salt samples were obtained from the walls of a pilot well in Hubei province China. The natural salt shows alternating layers of rock salt, anhydrite, mudstone and glauberite. Cylindrical samples, 50 mm diameter and 85 mm long, were prepared with layer interfaces oriented vertical, horizontal or obliquely to the core axis. Tests were conducted at room temperature and a confining pressure of 20 and (for shallower depth) 10 MPa, representing in-situ conditions. Axial deformation was performed using a triaxial machine in the HPT-laboratory at Utrecht. Compaction/dilation was measured using a servo control dilatometer for confining pressure control, and, in conjunction, the permeability was measured using Argon gas transient step permeameter. The samples were deformed at a constant displacement rate of 1 µm/s. After reaching 10, 20 and 30 MPa differential stress, deformation was halted and permeability was measured parallel to the compositional interfaces for each of the three geometries. Overall, it was found that during deformation, no shear slippage occurred at interface and the bulk permeability of most specimens decreased, where the absolute permeability value (found in the range 10-15 to <10-21 m2) depending upon the orientation of the bedding interface and composition of the sample. All samples showed a decrease in volume with axial strain, demonstrating progressive compaction with increasing stress values. The microstructural observation revealed local dilatancy near the interface, but this was masked by the bulk compaction as measured by the dilatometer. The results imply that the formation can be a potential candidate for gas storage, with anticipation that deep walls will be lesser permeable.

Translational safety biomarkers of colonic barrier integrity in the rat.

PubMed

Erkens, Tim; Bueters, Ruud; van Heerden, Marjolein; Cuyckens, Filip; Vreeken, Rob; Goeminne, Nick; Lammens, Lieve

2018-05-20

The intestinal barrier controls intestinal permeability, and its disruption has been associated with multiple diseases. Therefore, preclinical safety biomarkers monitoring barrier integrity are essential during the development of drugs targeting the intestines, particularly if starting treatment early after onset of disease. Classical toxicology endpoints are not sensitive enough and therefore our objective was to identify non-invasive markers enabling early in vivo detection of colonic barrier perturbation. Male Sprague-Dawley rats were dosed intracolonically via the rectum, using sodium caprate or ibuprofen as tool compounds to alter barrier integrity. Several potentially translational biomarkers and probe molecules related to permeability, inflammation or tissue damage were evaluated, using various analytical platforms, including immunoassays, targeted metabolomics and highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry. Several markers were identified that allow early in vivo detection of colonic barrier integrity changes, before histopathological evidence of tissue damage. The most promising permeability markers identified were plasma fluorescein isothiocyanate-dextran 4000 and a lactulose/mannitol/sucralose mixture in urine. These markers showed maximum increases over 100-fold or approximately 10-50-fold, respectively. Intracolonic administration of the above probe molecules outperformed oral administration and inflammatory or other biomarkers, such as α 2 -macroglobulin, calprotectin, cytokines, prostaglandins and a panel of metabolic molecules to identify early and subtle changes in barrier integrity. However, optimal timing of probe administration and sample collection is important for all markers evaluated. Inclusion of these probe molecules in preclinical toxicity studies might aid in risk assessment and the design of a clinical biomarker plan, as several of these markers have translational potential. Copyright © 2018 John Wiley & Sons, Ltd.

Cisplatin impairs rat liver mitochondrial functions by inducing changes on membrane ion permeability: prevention by thiol group protecting agents.

PubMed

Custódio, José B A; Cardoso, Carla M P; Santos, Maria S; Almeida, Leonor M; Vicente, Joaquim A F; Fernandes, Maria A S

2009-05-02

Cisplatin (CisPt) is the most important platinum anticancer drug widely used in the treatment of head, neck, ovarian and testicular cancers. However, the mechanisms by which CisPt induces cytotoxicity, namely hepatotoxicity, are not completely understood. The goal of this study was to investigate the influence of CisPt on rat liver mitochondrial functions (Ca(2+)-induced mitochondrial permeability transition (MPT), mitochondrial bioenergetics, and mitochondrial oxidative stress) to better understand the mechanism underlying its hepatotoxicity. The effect of thiol group protecting agents and some antioxidants against CisPt-induced mitochondrial damage was also investigated. Treatment of rat liver mitochondria with CisPt (20nmol/mg protein) induced Ca(2+)-dependent mitochondrial swelling, depolarization of membrane potential (DeltaPsi), Ca(2+) release, and NAD(P)H fluorescence intensity decay. These effects were prevented by cyclosporine A (CyA), a potent and specific inhibitor of the MPT. In the concentration range of up to 40nmol/mg protein, CisPt slightly inhibited state 3 and stimulated state 2 and state 4 respiration rates using succinate as respiratory substrate. The respiratory indexes, respiratory control ratio (RCR) and ADP/O ratios, the DeltaPsi, and the ADP phosphorylation rate were also depressed. CisPt induced mitochondrial inner membrane permeabilization to protons (proton leak) but did not induce significant changes on mitochondrial H(2)O(2) generation. All the effects induced by CisPt on rat liver mitochondria were prevented by thiol group protecting agents namely, glutathione (GSH), dithiothreitol (DTT), N-acetyl-L-cysteine (NAC) and cysteine (CYS), whereas superoxide-dismutase (SOD), catalase (CAT) and ascorbate (ASC) were without effect. In conclusion, the anticancer drug CisPt: (1) increases the sensitivity of mitochondria to Ca(2+)-induced MPT; (2) interferes with mitochondrial bioenergetics by increasing mitochondrial inner membrane permeabilization to H(+); (3) does not significantly affect H(2)O(2) generation by mitochondria; (4) its mitochondrial damaging effects are protected by thiol group protecting agents. Based on these conclusions, it is possible to hypothesise that small changes on the redox-status of thiol groups, affecting membrane permeability to cations (Ca(2+) and H(+)) underlie CisPt-induced liver mitochondrial damage, putatively responsible for its hepatotoxicity. Therefore, we propose that CisPt-induced mitochondrial damage and consequent hepatotoxicity could be prevented by using thiol group protecting agents as therapeutic adjuvants.

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.

PubMed

Rottenberg, Hagai; Hoek, Jan B

2017-10-01

Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Sirtuin 5 as a novel target to blunt blood-brain barrier damage induced by cerebral ischemia/reperfusion injury.

PubMed

Diaz-Cañestro, Candela; Merlini, Mario; Bonetti, Nicole R; Liberale, Luca; Wüst, Patricia; Briand-Schumacher, Sylvie; Klohs, Jan; Costantino, Sara; Miranda, Melroy; Schoedon-Geiser, Gabriele; Kullak-Ublick, Gerd A; Akhmedov, Alexander; Paneni, Francesco; Beer, Jürg H; Lüscher, Thomas F; Camici, Giovanni G

2018-06-01

In acute ischemic stroke (AIS) patients, impaired blood-brain barrier (BBB) integrity is associated with hemorrhagic transformation and worsened outcome. Yet, the mechanisms underlying these relationships are poorly understood and consequently therapeutic strategies are lacking. This study sought to determine whether SIRT5 contributes to BBB damage following I/R brain injury. SIRT5 knockout (SIRT5 -/- ) and wild type (WT) mice underwent transient middle cerebral artery (MCA) occlusion (tMCAO) followed by 48h of reperfusion. Genetic deletion of SIRT5 decreased infarct size, improved neurological function and blunted systemic inflammation following stroke. Similar effects were also achieved by in vivo SIRT5 silencing. Immunohistochemical analysis revealed decreased BBB leakage and degradation of the tight junction protein occludin in SIRT5 -/- mice exposed to tMCAO as compared to WT. In primary human brain microvascular endothelial cells (HBMVECs) exposed to hypoxia/reoxygenation (H/R), SIRT5 silencing decreased endothelial permeability and upregulated occludin and claudin-5; this effect was prevented by the PI3K inhibitor wortmannin. Lastly, SIRT5 gene expression was increased in peripheral blood monocytes (PBMCs) of AIS patients at 6h after onset of stroke compared to sex- and age-matched healthy controls. SIRT5 is upregulated in PBMCs of AIS patients and in the MCA of WT mice exposed to tMCAO; SIRT5 mediates I/R-induced brain damage by increasing BBB permeability through degradation of occludin. This effect was reproduced in HBMVECs exposed to H/R, mediated by the PI3K/Akt pathway. Our findings shed new light on the mechanisms of I/R-dependent brain damage and suggest SIRT5 as a novel therapeutic target. Copyright © 2017 Elsevier B.V. All rights reserved.

Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

PubMed Central

Lee, Chao Yu; Wang, Liang-Fei; Wu, Chun-Hu; Ke, Chia-Hua; Chen, Szu-Fu

2014-01-01

Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg−1) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect. PMID:25546475

Enantioselective oxidative stress and oxidative damage caused by Rac- and S-metolachlor to Scenedesmus obliquus.

PubMed

Liu, Huijun; Xia, YiLu; Cai, Weidan; Zhang, Yina; Zhang, Xiaoqiang; Du, Shaoting

2017-04-01

The rational use and environmental security of chiral pesticides has gained the interest of many researchers. The enantioselective effects of Rac- and S-metolachlor on oxidative stress in Scenedesmus obliquus were determined in this study. Stronger green fluorescence was observed in response to S-metolachlor treatment than to Rac-metolachlor treatment, suggesting that more reactive oxygen species (ROS) were stimulated by S-metolachlor. ROS levels following S-metolachlor treatment were 1.92-, 8.31-, and 1.08-times higher than those observed following Rac-metolachlor treatment at 0.1, 0.2, and 0.3 mg/L, respectively. Superoxide dismutase (SOD) and catalase (CAT) were stimulated with increasing herbicide concentrations, with S-metolachlor exhibiting a greater effect. Oxidative damage in terms of chlorophyll (Chl) content, cellular membrane permeability, and cellular ultrastructures of S. obliquus were investigated. Chla and Chlb contents in algae treated with Rac-metolachlor were 2-6-fold higher than those in algae treated with S-metolachlor at 0.1, 0.2, and 0.3 mg/L. The cellular membrane permeability of algae exposed to 0.3 mg/L Rac- and S-metolachlor was 6.19- and 42.5-times that of the control. Correlation analysis implied that ROS are the major factor responsible for the oxidative damage caused by Rac- and S-metolachlor. Damage to the chloroplasts and cell membrane of S. obliquus, low production of starch granules, and an increased number of vacuoles were observed upon ultrastructural morphology analysis by transmission electron microscope. These results indicate that S-metolachlor has a greater effect on S. obliquus than Rac-metolachlor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

PubMed

Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

2015-02-05

Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Ultrasonic survey and monitoring of the excavation damaged zone in callovo-oxfordian argillaceous rock

NASA Astrophysics Data System (ADS)

Balland, C.; Morel, J.

2010-12-01

The mining of galleries in geological claystones formation induces a stress redistribution that can cause a microfissuration of the rock around the works which, by coalescence, may generate macro field fractures. In this area called EDZ (Excavation Damaged Zone), permeability is expected to increase drastically. Those induced cracking along with increased permeability, shall be taken into account in safety assessment of deep geological disposal. Ultrasonic survey and monitoring experiments have been performed in the Underground Research Laboratory of Meuse/Haute-Marne to contribute to the understanding of the extension and evolution of this damage. Ultrasonic devices have been deployed around shaft, gallery, slot and borehole to characterize the initiation, the extension and the level of the EDZ, P-wave velocity being very sensitive to the mechanical rock perturbations. The analysis of spatial and temporal velocity field changes gave reliable information on the cracks characteristics of the especially about their opening or their preferential orientation. The results provided by an ultrasonic device around shaft mine by test highlighted the initialization and extension of the damage as the shaft front proceeded. They also showed a polarisation of the velocity field and an oscillation of the transversal isotropy with a preferential orientation of the stress release and the microcracking. Otherwise, with a new automatic and ultrasonic probe, we have found around a borehole that the damage zone extends up to 0.175 diameter of depth with an anisotropic damage pattern oriented according to the regional stress field (Figure 1). Nevertheless, the evolution of this damaged zone is still not well known at longer term, particularly under the influence of parameters such as the reconfining rock in contact with a rigid concrete surface. Is it possible that cracks close up significantly toward their seal? Induced mechanical perturbations are in this case much weaker than those generated by the excavation itself. A new ultrasonic experiment has been designed to be more sensitive to the frequency modulation of the P and S-wave sources. The purpose is to determine on site the dynamic elastic stiffness and the corresponding crack density tensors change before and during the resaturation and reconfining of the damaged and undamaged excavation vicinity. P-wave velocity field around a vertical borehole

Osmotic tolerance limits and membrane permeability characteristics of stallion spermatozoa treated with cholesterol.

PubMed

Glazar, Amanda I; Mullen, Steven F; Liu, Jun; Benson, James D; Critser, John K; Squires, Edward L; Graham, James K

2009-10-01

Stallion spermatozoa exhibit osmotic damage during the cryopreservation process. Recent studies have shown that the addition of cholesterol to spermatozoal membranes increases the cryosurvival of bull, ram and stallion spermatozoa, but the exact mechanism by which added cholesterol improves cryosurvival is not understood. The objectives of this study were to determine if adding cholesterol to stallion sperm membranes alters the osmotic tolerance limits and membrane permeability characteristics of the spermatozoa. In experiment one, stallion spermatozoa were treated with cholesterol-loaded cyclodextrin (CLC), subjected to anisotonic solutions and spermatozoal motility analyzed. The spermatozoa were then returned to isotonic conditions and the percentages of motile spermatozoa again determined. CLC treatment increased the osmotic tolerance limit of stallion spermatozoa in anisotonic solutions and when returned to isotonic conditions. The second and third experiments utilized an electronic particle counter to determine the plasma membrane characteristics of stallion spermatozoa. In experiment two, stallion spermatozoa were determined to behave as linear osmometers. In experiment three, spermatozoa were treated with CLC, incubated with different cryoprotectants (glycerol, ethylene glycol or dimethyl formamide) and their volume excursions measured during cryoprotectant removal at 5 degrees and 22 degrees C. Stallion spermatozoa were less permeable to the cryoprotectants at 5 degrees C than 22 degrees C. Glycerol was the least permeable cryoprotectant in control cells. The addition of CLC's to spermatozoa increased the permeability of stallion spermatozoa to the cryoprotectants. Therefore, adding cholesterol to spermatozoal membranes reduces the amount of osmotic stress endured by stallion spermatozoa during cryopreservation.

Investigation on the Permeability Evolution of Gypsum Interlayer Under High Temperature and Triaxial Pressure

NASA Astrophysics Data System (ADS)

Tao, Meng; Yechao, You; Jie, Chen; Yaoqing, Hu

2017-08-01

The permeability of the surrounding rock is a critical parameter for the designing and assessment of radioactive waste disposal repositories in the rock salt. Generally, in the locations that are chosen for radioactive waste storage, the bedded rock salt is a sedimentary rock that contains NaCl and Na2SO4. Most likely, there are also layers of gypsum ( {CaSO}_{ 4} \\cdot 2 {H}_{ 2} {O)} present in the salt deposit. Radioactive wastes emit a large amount of heat and hydrogen during the process of disposal, which may result in thermal damage of the surrounding rocks and cause a great change in their permeability and tightness. Therefore, it is necessary to investigate the permeability evolution of the gypsum interlayer under high temperature and high pressure in order to evaluate the tightness and security of the nuclear waste repositories in bedded rock salt. In this study, a self-designed rock triaxial testing system by which high temperature and pressure can be applied is used; the μCT225kVFCB micro-CT system is also employed to investigate the permeability and microstructure of gypsum specimens under a constant hydrostatic pressure of 25 MPa, an increasing temperature (ranging from 20 to 650 °C), and a variable inlet gas pressure (1, 2, 4, 6 MPa). The experimental results show: (a) the maximum permeability measured during the whole experiment is less than 10-17 m2, which indicates that the gypsum interlayer has low permeability under high temperature and pressure that meet the requirements for radioactive waste repository. (b) Under the same temperature, the permeability of the gypsum specimen decreases at the beginning and then increases as the pore pressure elevates. When the inlet gas pressure is between 0 and 2 MPa, the Klinkenberg effect is very pronounced. Then, as the pore pressure increases, the movement behavior of gas molecules gradually changes from free motion to forced directional motion. So the role of free movement of gas molecules gradually reduced, which eventually leads to a decrease in permeability. When the inlet gas pressure is between 2 and 6 MPa, the Klinkenberg effect dribbles away, and the gas flow gradually obeys to the Darcy's law. Hence, the permeability increased with the increase in inlet gas pressure. (c) The curve of permeability versus temperature is divided into five stages based on its gradient. In the temperature range of 20-100 °C, the permeability of gypsum decreased slowly when the temperature decreased. From 100 to 200 °C, the permeability of gypsum increased dramatically when the temperature increased. However, a dramatic increase in permeability was observed from 200 to 450 °C. Subsequently, in the temperature range of 450-550 °C, due to closure of pores and fractures, the permeability of the specimens slowly lessened when the temperature increased. From 550 to 650 °C, the permeability of gypsum slightly increased when the temperature increased; (d) the micro-cracks and porosity obtained from the CT images show a high degree of consistency to the permeability evolution; (e) when compared to the permeability evolutions of sandstone, granite, and lignite, gypsum exhibits a stable evolution trend of permeability and has a much greater threshold temperature when its permeability increases sharply. The results of the paper may provide essential and valuable references for the design and construction of high-level radioactive wastes repository in bedded salt rock containing gypsum interlayers.

Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

NASA Astrophysics Data System (ADS)

Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

2015-11-01

Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

Effects of clay dispersion on aquifer storage and recovery in coastal aquifers

USGS Publications Warehouse

Konikow, Leonard F.; August, L.L.; Voss, C.I.

2001-01-01

Cyclic injection, storage, and withdrawal of freshwater in brackish aquifers is a form of aquifer storage and recovery (ASR) that can beneficially supplement water supplies in coastal areas. A 1970s field experiment in Norfolk, Virginia, showed that clay dispersion in the unconsolidated sedimentary aquifer occurred because of cation exchange on clay minerals as freshwater displaced brackish formation water. Migration of interstitial clay particles clogged pores, reduced permeability, and decreased recovery efficiency, but a calcium preflush was found to reduce clay dispersion and lead to a higher recovery efficiency. Column experiments were performed in this study to quantify the relations between permeability changes and clay mineralogy, clay content, and initial water salinity. The results of these experiments indicate that dispersion of montmorillonite clay is a primary contributor to formation damage. The reduction in permeability by clay dispersion may be expressed as a linear function of chloride content. Incorporating these simple functions into a radial, cross-sectional, variable-density, ground-water flow and transport model yielded a satisfactory simulation of the Norfolk field test - and represented an improvement over the model that ignored changes in permeability. This type of model offers a useful planning and design tool for ASR operations in coastal clastic aquifer systems.

Polymer-Layered Silicate Nanocomposites for Cryotank Applications

NASA Technical Reports Server (NTRS)

Miller, Sandi G.; Meador, Michael A.

2007-01-01

Previous composite cryotank designs have relied on the use of conventional composite materials to reduce microcracking and permeability. However, revolutionary advances in nanotechnology derived materials may enable the production of ultra-lightweight cryotanks with significantly enhanced durability and damage tolerance, as well as reduced propellant permeability. Layered silicate nanocomposites are especially attractive in cryogenic storage tanks based on results that have been reported for epoxy nanocomposite systems. These materials often exhibit an order of magnitude reduction in gas permeability when compared to the base resin. In addition, polymer-silicate nanocomposites have been shown to yield improved dimensional stability, strength, and toughness. The enhancement in material performance of these systems occurs without property trade-offs which are often observed in conventionally filled polymer composites. Research efforts at NASA Glenn Research Center have led to the development of epoxy-clay nanocomposites with 70% lower hydrogen permeability than the base epoxy resin. Filament wound carbon fiber reinforced tanks made with this nanocomposite had a five-fold lower helium leak rate than the corresponding tanks made without clay. The pronounced reduction observed with the tank may be due to flow induced alignment of the clay layers during processing. Additionally, the nanocomposites showed CTE reductions of up to 30%, as well as a 100% increase in toughness.

Towards cavitation-enhanced permeability in blood vessel on a chip

NASA Astrophysics Data System (ADS)

De Luca, R.; Silvani, G.; Scognamiglio, C.; Sinibaldi, G.; Peruzzi, G.; Chinappi, M.; Kiani, M. F.; Casciola, C. M.

2017-08-01

The development of targeted delivery systems releasing pharmaceutical agents directly at the desired site of action may improve their therapeutic efficiency while minimizing damage to healthy tissues, toxicity to the patient and drug waste. In this context, we have developed a bio-inspired microdevice mimicking the tumour microvasculature which represents a valuable tool for assessing the enhancement of blood vessel permeability due to cavitation. This novel system allows us to investigate the effects of ultrasound-driven microbubbles that temporarily open the endothelial intercellular junctions allowing drug to extravasate blood vessels into tumour tissues. The blood vessel on a chip consists of a tissue chamber and two independent vascular channels (width 200 µm, height 100 µm, length 2762 µm) cultured with endothelial cells placed side-by-side and separated by a series of 3 µm pores. Its geometry and dimensions mimic the three-dimensional morphology, size and flow characteristics of microvessels in vivo. The early stage of this project had a twofold objective: 1. To define the protocol for culturing of Human Umbilical Vein Endothelial Cells (HUVECs) within the vascular channel; 2. To develop a fluorescence based microscopy technique for measuring permeability. We have developed a reliable and reproducible protocol to culture endothelial cells within the artificial vessels in a realistic manner: HUVECs show the typical elongated shape in the direction of flow, exhibit tight junction formation and form a continuous layer with a central lumen that completely covers the channels wall. As expected, the permeability of cell-free device is higher than the one cultured with HUVECs in the vascular channels. The proposed blood vessel on a chip and the permeability measurement protocol have a significant potential to allow for the study of cavitation-enhanced permeability of the endothelium and improve efficiency in screening drug delivery systems.

Influence of loading and unloading velocity of confining pressure on strength and permeability characteristics of crystalline sandstone

NASA Astrophysics Data System (ADS)

Zhang, Dong-ming; Yang, Yu-shun; Chu, Ya-pei; Zhang, Xiang; Xue, Yan-guang

2018-06-01

The triaxial compression test of crystalline sandstone under different loading and unloading velocity of confining pressure is carried out by using the self-made "THM coupled with servo-controlled seepage apparatus for containing-gas coal", analyzed the strength, deformation and permeability characteristics of the sample, the results show that: with the increase of confining pressures loading-unloading velocity, Mohr's stress circle center of the specimen shift to the right, and the ultimate intensity, peak strain and residual stress of the specimens increase gradually. With the decrease of unloading velocity of confining pressure, the axial strain, the radial strain and the volumetric strain of the sample decrease first and then increases, but the radial strain decreases more greatly. The loading and unloading of confining pressure has greater influence on axial strain of specimens. The deformation modulus decreases rapidly with the increase of axial strain and the Poisson's ratio decreases gradually at the initial stage of loading. When the confining pressure is loaded, the deformation modulus decrease gradually, and the Poisson's ratio increases gradually. When the confining pressure is unloaded, the deformation modulus increase gradually, and the Poisson's ratio decreases gradually. When the specimen reaches the ultimate intensity, the deformation modulus decreases rapidly, while the Poisson's ratio increases rapidly. The fitting curve of the confining pressure and the deformation modulus and the Poisson's ratio in accordance with the distribution of quadratic polynomial function in the loading-unloading confining pressure. There is a corresponding relationship between the evolution of rock permeability and damage deformation during the process of loading and unloading. In the late stage of yielding, the permeability increases slowly, and the permeability increases sharply after the rock sample is destroyed. Fitting the permeability and confining pressure conform to the variation law of the exponential function.

PO43 Removal by and Permeability of Industrial Byproducts and Minerals: Granulated Blast Furnace Slag, Cement Kiln Dust, Coconut Shell Activated Carbon, Silica Sand and Zeolite

USDA-ARS?s Scientific Manuscript database

Excess aqueous concentration of phosphate degrades the overall water quality of the receiving surface waters in a cumulatively damaging process referred to as eutrophication. Adsorption of excess phosphate has proven to be the most effective, and economical methods of phosphate removal from such wat...

[Hepatocyte apoptosis and mitochondrial permeability transition pore opening in rats with nonalcoholic fatty liver].

PubMed

Kang, Min; Li, Sen; Zhong, Dejun; Yang, Zhimin; Li, Peng

2013-07-01

To investigate the role of hepatocyte apoptosis and mitochondrial permeability transition pore (MPTP) opening in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Thirty male SD rats were randomized into normal diet group and high-fat diet group. At 4, 8 and 12 week of feeding. The hepatocyte apoptosis index (AI) was measured using flow cytometry, and MPTP opening was evaluated with ultraviolet spectrophotometry. Immunohistochemistry was employed to detect hepatic expressions of Bcl-2 and Bax, and Western blotting was used to detect Bax protein expression changes. High-fat feeding resulted in significantly increased hepatocyte AI at 4-12 weeks and gradually increased MPTP opening. In the high-fat diet group, hepatic Bcl-2 expression was detected but the positive cell number remained stable, whereas Bax-positive cell number increased steadily with time with progressively increased intensity of Bax protein expression, resulting in gradually decreased Bcl-2/Bax ratio. Hepatocyte apoptosis occurs in the rat model of NAFLD in close correlation with mitochondrial damage. Increased MPTP opening as the result of increased Bax expression and aberrant Bcl-2/Bax ratio is an important mechanism of hepatocyte mitochondrial damage in NAFLD.

Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

PubMed Central

2014-01-01

Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM. PMID:24467887

Intravesical application of rebamipide promotes urothelial healing in a rat cystitis model.

PubMed

Funahashi, Yasuhito; Yoshida, Masaki; Yamamoto, Tokunori; Majima, Tsuyoshi; Takai, Shun; Gotoh, Momokazu

2014-12-01

Rebamipide is used as a topical therapeutic agent for various organs. We examined the healing effects of intravesical rebamipide on damaged urothelium in a rat model of chemically induced cystitis. Hydrochloride was injected in the bladder of female Sprague Dawley® rats to induce cystitis. On days 1 and 4 rebamipide (1 or 10 mM) or vehicle was administered in the bladder and maintained for 1 hour. Histopathology, urothelial permeability, cystometrogram and nociceptive behaviors were evaluated on day 7. Also, tissue rebamipide concentrations after the 1-hour bladder instillation were quantified using high performance liquid chromatography. Intravesically administered rebamipide permeated the bladder, particularly in hydrochloride treated rats, and the pharmacologically effective tissue dose remained for greater than 6 hours. Bladder histological evaluation revealed polymorphological inflammatory cell infiltration and decreased positive staining for uroplakin 3A in hydrochloride treated rats. Scanning electron microscopy showed damaged tight junctions in the hydrochloride group. Evans blue absorption in the bladder wall was increased in hydrochloride treated rats. These findings, which were associated with urothelial injury and increased permeability, were dependently suppressed by the rebamipide treatment dose. Cystometrogram demonstrated that the intercontraction interval was shorter in hydrochloride treated rats but prolonged by rebamipide. The increased nociceptive behaviors observed after intravesical resiniferatoxin administration were also suppressed by rebamipide. Intravesical rebamipide accelerated the repair of damaged urothelium, protected urothelial barrier function and suppressed bladder overactivity and nociception. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Experimental scleral cross-linking increases glaucoma damage in a mouse model

PubMed Central

Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.

2014-01-01

The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424

Poly(ADP-ribose) polymerase-1 regulates microglia mediated decrease of endothelial tight junction integrity.

PubMed

Mehrabadi, Abbas Rezaeian; Korolainen, Minna A; Odero, Gary; Miller, Donald W; Kauppinen, Tiina M

2017-09-01

Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells. Unstimulated microglia promoted expression of tight junction proteins (TJPs), zonula ocluden-1 (ZO-1) and occludin in co-cultured endothelia cells, whereas Aβ-stimulated microglia reduced endothelial expression of ZO-1 and occludin. Astrocytes co-cultured with microglia showed elevated glial fibrillary acidic protein (GFAP) expression, which was further increased if microglia had been stimulated with Aβ. Aβ induced microglial release of nitric oxide (NO) and tumour necrosis factor alpha (TNFα), which resulted in reduced endothelial expression of TJPs and increased paracellular permeability. Microglial PARP-1 inhibition attenuated these Aβ-induced events. These findings demonstrate that PARP-1 mediated microglial responses (NO and TNFα) can directly reduce BBB integrity by promoting TJP degradation, increasing endothelial cell permeability and inducing astrogliosis. PARP-1 as a modulator of microglial phenotype can prevent microglial BBB damaging events, and thus is a potential therapeutic target. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of cancer cell permeability control on the efficiency of cell damage through surface plasmon resonance of gold nanoparticle (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hsiao, Jen-Hung; Yu, Jian-He; He, Yulu; Tu, Yi-Chou; Hua, Wei-Hsiang; Low, Meng Chun; Hsieh, Cheng-Che; Kiang, Yean-Woei; Yang, Chih-Chung

2017-02-01

Cancer cell killing efficiencies based on the photothermal effect caused by the surface plasmon resonance of metal nanoparticles (NPs) and the photodynamic effect caused by the singlet oxygen generation of a photosensitizer rely on the cell uptake efficiency of metal NP and photosensitizer. Perforation and heating can increase cell membrane permeability and hence can increase the cell uptake efficiency of NPs and drugs. In this paper, we demonstrate the variations of the cell damage efficiency under the illuminations of different lasers, which can produce mainly photothermal effect, mainly photodynamic effect, and mixed effect, when a pre-perforation and a pre-heating processes are applied. Au nanorings (NRIs) with their localized surface plasmon resonance wavelength around 1064 nm are used. The perforation process is undertaken by illuminating the cell samples by a femtosecond laser at 1064 nm with the power density lower than the cell damage threshold intensity. The heating process is implemented by illuminating cells with a low power continuous laser at 1064 nm. It is found that with the pre-perforation and pre-heating processes, the photodynamic effect is enhanced because the internalized Au NRI number and hence the internalized photosensitizer (AlPcS) molecule number are increased. However, the photothermal effect can be reduced because the adsorbed Au NRIs on cell membrane are effectively internalized during the pre-perforation and pre-heating processes. The photothermal effect is more effective when Au NRIs are adsorbed on cell membrane.

Water Vapor Permeation in Plastics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, Paul E.; Kouzes, Richard T.

Polyvinyl toluene (PVT) and polystyrene (PS) (referred to as “plastic scintillator”) are used for gamma ray detectors. A significant decrease in radiation detection performance has been observed in some PVT-based gamma-ray detectors in systems in outdoor environments as they age. Recent studies have revealed that plastic scintillator can undergo an environmentally related material degradation that adversely affects gamma ray detection performance under certain conditions and histories. A significant decrease in sensitivity has been seen in some gamma-ray detectors in some systems as they age. The degradation of sensitivity of plastic scintillator over time is due to a variety of factors,more » and the term “aging” is used to encompass all factors. Some plastic scintillator samples show no aging effects (no significant change in sensitivity over more than 10 years), while others show severe aging (significant change in sensitivity in less than 5 years). Aging effects arise from weather (variations in heat and humidity), chemical exposure, mechanical stress, light exposure, and loss of volatile components. The damage produced by these various causes can be cumulative, causing observable damage to increase over time. Damage may be reversible up to some point, but becomes permanent under some conditions. The objective of this report is to document the phenomenon of permeability of plastic scintillator to water vapor and to derive the relationship between time, temperature, humidity and degree of water penetration in plastic. Several conclusions are documented about the properties of water permeability of plastic scintillator.« less

Absence of Dystrophin Disrupts Skeletal Muscle Signaling: Roles of Ca2+, Reactive Oxygen Species, and Nitric Oxide in the Development of Muscular Dystrophy

PubMed Central

Allen, David G.; Whitehead, Nicholas P.; Froehner, Stanley C.

2015-01-01

Dystrophin is a long rod-shaped protein that connects the subsarcolemmal cytoskeleton to a complex of proteins in the surface membrane (dystrophin protein complex, DPC), with further connections via laminin to other extracellular matrix proteins. Initially considered a structural complex that protected the sarcolemma from mechanical damage, the DPC is now known to serve as a scaffold for numerous signaling proteins. Absence or reduced expression of dystrophin or many of the DPC components cause the muscular dystrophies, a group of inherited diseases in which repeated bouts of muscle damage lead to atrophy and fibrosis, and eventually muscle degeneration. The normal function of dystrophin is poorly defined. In its absence a complex series of changes occur with multiple muscle proteins showing reduced or increased expression or being modified in various ways. In this review, we will consider the various proteins whose expression and function is changed in muscular dystrophies, focusing on Ca2+-permeable channels, nitric oxide synthase, NADPH oxidase, and caveolins. Excessive Ca2+ entry, increased membrane permeability, disordered caveolar function, and increased levels of reactive oxygen species are early changes in the disease, and the hypotheses for these phenomena will be critically considered. The aim of the review is to define the early damage pathways in muscular dystrophy which might be appropriate targets for therapy designed to minimize the muscle degeneration and slow the progression of the disease. PMID:26676145

Development of an evaporation-optimized and water-permeable pavement

NASA Astrophysics Data System (ADS)

Starke, P.; Göbel, P.; Coldewey, W. G.

2009-04-01

During recent decades, urban areas have been threatened more frequently by flood events. Furthermore, the potential for damage from these events has increased on average. The construction of houses, streets and parking lots has caused this trend by sealing the ground surface, i.e. these water-impermeable areas reduce the natural infiltration and evaporation-rates, and in some cases it is even completely stopped. The consequence is the so called "urban water cycle". Water from precipitation cannot be stored anywhere and so there is an immediate and very high surface run-off effect. Especially after intense rain events, canalisations and sewage-treatment plants are overloaded and this leads to higher costs for water treatment and to environmental damage. A practical solution to this problem is the use of water-permeable pavements. Here higher infiltration rates lead to a groundwater recharge that is greater than that of natural soils. The consequences from using these surfaces are already noticeable in many places through increasing groundwater levels. These increases cause damage to buildings. A second difference from a natural-soil water-balance is a lower evapotranspiration rate. Up to now the evaporation rates for water-permeable pavements has not been established accurately. The aim of the applied research project at the University of Muenster, which is sponsored by the DBU (The German Federal Environmental Foundation), is to gain knowledge of urban evaporation rates and of water-permeable surfaces, especially water-permeable pavements. Water-permeable pavements consist of the paving stone surface and the two sub-base layers below. Pre-investigations show that evaporation can be influenced by the complete sub-base. Therefore, the first step was to investigate which materials are used for sub-base construction. All in all, 27 materials were collected from throughout Germany and these materials were then tested (in terms of physical and hydraulic attributes) in the soil-mechanics laboratory of the University of Muenster. For their street construction useability, and having regard to evaporation, a selection of appropriate materials were built into a test field. The test field consisted of seven hexagonal areas each about 10 m2 large, which are placed in a honeycomb manner. The evaporation measurements are carried out with a WERNER tunnel-evaporation gauge (TUV) which is able to detect the actual evaporation rate. Its functional principle also allows a direct comparison between the middle reference area and one outer area of the test field. Every measuring period lasts one week and after that the TUV is moved to between the next outer area and the reference area. So the TUV rotates over the whole test field and every measuring area is covered by a measurement. In addition, a Hellman rain-gauge near the test field enables the measurement of a direct precipitation-evaporation ratio. Since the start of the measurements in July 2008, the first results collected showed that measureable differences in evaporation rates could be detected after a few measuring periods, i.e. the differences are up to 32% between the reference area and one outer area. In July 2009, the six outer measuring areas of the test field will be replaced and, based on the actual results collected, the sub-base layers will be replaced by an evaporation-optimized sub-base. The new outer measuring areas will only differ in terms of a different paving-stone surface. These paving stones are actually under developement and under laboratory testing (i.e. permeability, porosity, capillary water and evaporationrates), and so they will be evaporation-opimized. The open-air test in the test field is to assure and compare the evaporation rates. As a final result, the evaporation-optimized and water-permeable pavement and the knowledge of its exact drainage ratio will allow city planners or architects to build water-permeable streets with due regard to the respective area-specific conditions. This new developed pavement is an approximation to the water balance of a natural soil. In this way, the danger of flooding can be further reduced in urban areas.

Hydromechanical Behaviour of Unconsolidated Granular Materials under Proportional Triaxial Compression Tests

NASA Astrophysics Data System (ADS)

Nguyen, V.; Gland, N. F.; Dautriat, J.; Guelard, J.; David, C.

2010-12-01

During the production of petroleum reservoirs, compaction due to depletion (pore fluid pressure reduction) can lead to emphasis of natural permeability anisotropy and significant permeability reduction. Under such effective stress increase, weakly consolidated reservoirs will undergo strong deformation inducing important modifications of the transport properties, which control the fluid flows in the reservoir and the productivity of the wells. Classically the mechanical loadings applied in the laboratory are either hydrostatic or deviatoric at constant confining pressure; however the 'in-situ' stress paths experienced by the reservoirs differ; it is thus important to perform loading tests with more appropriate conditions such as ‘proportional triaxial’ and ‘oedometric’. This study focuses on the elastoplatic behaviour of non to weakly consolidated reservoir rocks (analogues) and the influence of the stress path (K=ΔσH/ΔσV) on the evolutions of porosity and permeability. Generally, permeability of pourous rocks evolves in three stages: (1) initial decrease related to compaction (soft rocks) or closing of pre-existing microflaws (compact rocks), (2) small reduction associated to the 'linear' deformation regime, (3) drop due to a strong compaction linked to porosity collapse and grain crushing mechanisms. The intensity of this reduction depends on the stress path coefficient, the grain sharpness and the granular texture. We use a triaxial cell (maximum axial load of 80kN and maximum confinement of 69MPa) to perform proportional triaxial compression tests (0

Forecasting Frost Damage: Follow the Water

NASA Astrophysics Data System (ADS)

Rempel, A. W.

2015-12-01

Frost damage takes place when the pressure exerted against pore walls exceeds the cohesive strength of water-infiltrated rock and causes cracks to extend. Elegant theoretical treatments supported by meticulous field and laboratory observations have combined to unravel the basic mechanical and thermodynamic controls in idealized systems. Frost damage is most vigorous when conditions are cold enough that the net pressure exerted against the pore walls can cause crack extension, yet warm enough to enable the flow that supplies further ice growth in the newly opened space. This insight is applied here to develop practical geomorphic process laws for the effects of frost damage at the larger scales that are relevant for describing the evolution of landscapes. To this end, a direct connection is made between the intensity of frost damage and the porosity increase that results from gradients in water flux under conditions that are cold enough for ice-rock interactions to propagate cracks. This implies that the annual temperature variation at the ground surface can be combined with considerations of heat and mass transport to derive rigorous forecasts of the potential for frost damage that are tied to the increases in water mass that accompany solidification in porous rock. As an example, the image shows the depth-integrated porosity change λ promoted by crack growth at temperatures colder than -ΔTc over an annual cycle for different choices of mean annual temperature MAT and surface amplitude A (assuming a thermal diffusivity of 1 mm2/s and a power-law relationship between permeability and undercooling with exponent α=4, such that a base value of 10-14m2 is reached at a reference undercooling of 0.1 ºC). The abrupt onset in cracking once MAT decreases below a threshold is produced by the requirement that undercooling surpass ΔTc in order to generate sufficient pressures to propagate cracks. The eventual reduction and gradual tail in λ at colder MAT is produced by the clogging of the permeable pathways needed to supply additional water to propmote crack growth.

Increment of root membrane permeability caused by microcystins result in more elements uptake in rice (Oryza sativa).

PubMed

Cao, Qing; Steinman, Alan D; Yao, Lei; Xie, Liqiang

2017-11-01

We conducted an indoor culture experiment to evaluate the phytotoxic effect of microcystins (MCs) on rice. After a 30day exposure, MCs induced a clear inhibition in rice growth, as well as a disruption of its antioxidant system and lipid peroxidation. We observed an increase in root membrane permeability; the conductivity of the leakage solution of the roots at 50 and 500μgL -1 was significantly increased by 77% and 136%, respectively, compared to the control. Uptake of microelements (Fe, Mn, Cu and Zn) was generally not affected after the 30day exposure to MCs. In contrast, uptake of macroelements, with the exception of K, was stimulated by MCs. Ca content in roots exposed to 500μgL -1 showed the greatest increase, by 47%, compared to the control. We propose the following mechanisms to explain our experimental results: exposure of rice roots to MCs leads to root damage and loss of membrane integrity, resulting in greater permeability and uptake of elements. Copyright © 2017 Elsevier Inc. All rights reserved.

Freeze fracturing of elastic porous media: a mathematical model

PubMed Central

Vlahou, I.; Worster, M. G.

2015-01-01

We present a mathematical model of the fracturing of water-saturated rocks and other porous materials in cold climates. Ice growing inside porous rocks causes large pressures to develop that can significantly damage the rock. We study the growth of ice inside a penny-shaped cavity in a water-saturated porous rock and the consequent fracturing of the medium. Premelting of the ice against the rock, which results in thin films of unfrozen water forming between the ice and the rock, is one of the dominant processes of rock fracturing. We find that the fracture toughness of the rock, the size of pre-existing faults and the undercooling of the environment are the main parameters determining the susceptibility of a medium to fracturing. We also explore the dependence of the growth rates on the permeability and elasticity of the medium. Thin and fast-fracturing cracks are found for many types of rocks. We consider how the growth rate can be limited by the existence of pore ice, which decreases the permeability of a medium, and propose an expression for the effective ‘frozen’ permeability. PMID:25792954

Freeze fracturing of elastic porous media: a mathematical model.

PubMed

Vlahou, I; Worster, M G

2015-03-08

We present a mathematical model of the fracturing of water-saturated rocks and other porous materials in cold climates. Ice growing inside porous rocks causes large pressures to develop that can significantly damage the rock. We study the growth of ice inside a penny-shaped cavity in a water-saturated porous rock and the consequent fracturing of the medium. Premelting of the ice against the rock, which results in thin films of unfrozen water forming between the ice and the rock, is one of the dominant processes of rock fracturing. We find that the fracture toughness of the rock, the size of pre-existing faults and the undercooling of the environment are the main parameters determining the susceptibility of a medium to fracturing. We also explore the dependence of the growth rates on the permeability and elasticity of the medium. Thin and fast-fracturing cracks are found for many types of rocks. We consider how the growth rate can be limited by the existence of pore ice, which decreases the permeability of a medium, and propose an expression for the effective 'frozen' permeability.

Pre-treatment with vinpocetine protects against retinal ischemia.

PubMed

Nivison-Smith, Lisa; Khoo, Pauline; Acosta, Monica L; Kalloniatis, Michael

2017-01-01

Vinpocetine has been shown to have beneficial effects for tissues of the central nervous system subjected to ischemia and other related metabolic insults. We recently showed vinpocetine promotes glucose availability, prevents unregulated cation channel permeability and regulates glial reactivity when present during retinal ischemia. Less is known however about the ability of vinpocetine to protect against future ischemic insults. This study explores the effect of vinpocetine when used as a pre-treatment in an ex vivo model for retinal ischemia using cation channel permeability of agmatine (AGB) combined with immunohistochemistry as a measure for cell functionality. We found that vinpocetine pre-treatment reduced cation channel permeability and apoptotic marker immunoreactivity in the GCL and increased parvalbumin immunoreactivity of inner retinal neurons in the inner nuclear layer following ischemic insult. Vinpocetine pre-treatment also reduced Müller cell reactivity following ischemic insults of up to 120 min compared to untreated controls. Many of vinpocetine's effects however were transient in nature suggesting the drug can protect retinal neurons against future ischemic damage but may have limited long-term applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Possible role of substance P in the ischemia-reperfusion injury in the isolated rabbit lung.

PubMed

Arreola, José L; Vargas, Mario H; Segura, Patricia; Chávez, Jaime; Sommer, Bettina; Carvajal, Verónica; Montaño, Luis M

2004-07-27

The origin of the endothelial damage leading to the ischemia-reperfusion injury after lung transplantation has not been elucidated. We postulated that neurotransmitters released during the preservation of the donor lung might explain this vascular derangement. Thus, in isolated rabbit lungs preserved over 24 hours, we evaluated the release of acetylcholine (ACh) and substance P (SP), the activity of their major degrading enzymes, acetylcholinesterase (AChE) and neutral endopeptidase (NEP), and changes in the capillary permeability. Both neurotransmitters showed the highest release rate in the first 15 minutes, followed by a sharp exponential decrement at 1, 6, 12 and 24 hours. AChE and NEP activities showed no variation at these time intervals. Basal capillary permeability significantly increased (P<0.01) after 24 hours preservation with saline. This increased permeability was avoided (P<0.01) by the SP fragment 4-11 (an SP receptors antagonist), but not by atropine. These results suggest for the first time a pathogenic role of SP in the ischemia-reperfusion injury, and thus the potential usefulness of SP antagonists as additives in the lung preservation solutions should be explored.

Identification of Soil Properties and Organophosphate Residues From Agricultural Land in Wanasari Sub-District, Brebes, Indonesia

NASA Astrophysics Data System (ADS)

Joko, Tri; Anggoro, Sutrisno; Sunoko, Henna Rya; Rachmawati, Savitri

2018-02-01

Organophosphates have been used to eradicate pests and prevent losses from harvest failures caused by pest attack. It is undeniable that the organophosphate persist in soil. This study aims to identify the organophosphate residue and soil properties include pH, soil texture, and permeability. The soil samples were taken from cropland in 10 villages, Wanasari sub-district, Brebes, Indonesia. Organophosphate residue determined by gas chromatography using Flame Photometric Detector. Soil texture was determined by soil texture triangle from NRCS USDA, and the permeability value was determined by falling head method. The mean value of chlorpyrifos, profenofos, diazinon were 0.0078; 0.0388; 0.2271 mg/l respectively. The soil texture varies from clay, silt clay, loam, silt loam, and silt clay loam with permeability value at 10-7 with the soil pH value between 6.4 - 8.1. The results showed that organophosphate residues found in the soil and its potential affect the soil fertility decline. We recommend to conduct routine soil quality analysis to prevent soil damage in the agricultural environment.

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

PubMed Central

He, Quanguo; Liu, Jun; Liang, Jing; Liu, Xiaopeng; Li, Wen; Liu, Zhi; Ding, Ziyu; Tuo, Du

2018-01-01

The blood–brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability. PMID:29570659

Correlating Near-Source Rock Damage from Single-Hole Explosions to Seismic Waves (Postprint)

DTIC Science & Technology

2012-05-07

Technical Paper APPROVED FOR PUBLIC RELEASE; DISTRIBUTION IS UNLIMITED. AIR FORCE RESEARCH LABORATORY Space Vehicles Directorate...Space Vehicles Directorate 3550 Aberdeen Ave SE 3550 Aberdeen Ave SE 11. SPONSOR/MONITOR’S REPORT Kirtland AFB, NM 87117-5776...function of pressure, • Fluid permeability as a function of pressure, • Electrical resistivity as a function of pressure, and • Rock strength. The

Membrane damage during dilution, cooling and freezing-thawing of boar spermatozoa packaged in plastic bags.

PubMed

Ortman, K; Rodriguez-Martinez, H

1994-02-01

The objective of the present investigation was to determine the degree of membrane damage in boar spermatozoa during the course of a cryopreservation procedure, including thawing. Ejaculates from four fertile Swedish Yorkshire boars were frozen under controlled conditions in Teflon-plastic bags (2.5 ml) using 3% glycerol as cryoprotectant. Membrane integrity was monitored using supravital fluorescent dyes and confirmed by scanning electron microscopy. The results show that cooling to +5 degrees C significantly affected the permeability of the plasmalemma. Supercooling (-6 degrees C) during the freezing program did not further deteriorate the integrity of the spermatozoal membrane. The thawing procedure however, dramatically increased the frequency of spermatozoa with damaged plasma membranes. Thus particular attention must be paid on designing a better thawing procedure when dealing with boar semen frozen in plastic bags.

The Multi-Porosity Multi-Permeability and Electrokinetic Natures of Shales and Their Effects in Hydraulic Fracturing of Unconventional Shale Reservoirs

NASA Astrophysics Data System (ADS)

Liu, C.; Hoang, S. K.; Tran, M. H.; Abousleiman, Y. N.

2013-12-01

Imaging studies of unconventional shale reservoir rocks have recently revealed the multi-porosity multi-permeability nature of these intricate formations. In particular, the porosity spectrum of shale reservoir rocks often comprises of the nano-porosity in the organic matters, the inter-particle micro-porosity, and the macroscopic porosity of the natural fracture network. Shale is also well-known for its chemically active behaviors, especially shrinking and swelling when exposed to aqueous solutions, as the results of pore fluid exchange with external environment due to the difference in electro-chemical potentials. In this work, the effects of natural fractures and electrokinetic nature of shale on the formation responses during hydraulic fracturing are examined using the dual-poro-chemo-electro-elasticity approach which is a generalization of the classical Biot's poroelastic formulation. The analyses show that the presence of natural fractures can substantially increase the leak-off rate of fracturing fluid into the formation and create a larger region of high pore pressure near the fracture face as shown in Fig.1a. Due to the additional fluid invasion, the naturally fractured shale swells up more and the fracture aperture closes faster compared to an intrinsically low permeability non-fractured shale formation as shown in Fig.1b. Since naturally fractured zones are commonly targeted as pay zones, it is important to account for the faster fracture closing rate in fractured shales in hydraulic fracturing design. Our results also show that the presence of negative fixed charges on the surface of clay minerals creates an osmotic pressure at the interface of the shale and the external fluid as shown in Fig.1c. This additional Donnan-induced pore pressure can result in significant tensile effective stresses and tensile damage in the shale as shown in Fig.1d. The induced tensile damage can exacerbate the problem of proppant embedment resulting in more fracture closure and reduction of fracture length and productivity. The results also suggest that a fracturing fluid with appropriately designed salinity can minimize the chemically induced tensile damage and, thus, maximize the productivity from the created hydraulic fractures.

Characterization and monitoring of the excavation damaged zone in fractured gneisses of the Roselend tunnel, French Alps

NASA Astrophysics Data System (ADS)

Wassermann, J.; Sabroux, J. C.; Pontreau, S.; Bondiguel, S.; Guillon, S.; Richon, P.; Pili, E.

2011-04-01

The Roselend dead-end tunnel was excavated in the last fifties by blasting in the Méraillet crystalline rock mass located on the shore of an artificial reservoir lake in the French Alps. Successive emptying and filling of the reservoir lake induce mechanical deformation of the rock mass. Thus, this tunnel is an exceptional place to study the evolution of the damaged zone (due to the excavation, and named EDZ) under a periodic mechanical or hydraulic loading. From the perspective of radioactive waste isolation in deep geological strata, the EDZ transport properties, and their evolution with time, are of major importance. The purpose of this study is, on the one hand, to quantify the transport properties of the EDZ of the Roselend tunnel through permeability measurements and drill core observations; on the other hand, to monitor the response of the EDZ to external solicitations via borehole pressure measurements. The air permeability has been deduced from pneumatic tests performed along several boreholes. The permeability profiles and the observation of drill cores lead to an estimation of the extent of the EDZ, of about 1 m around the tunnel. The response of the EDZ to barometric pumping has been observed through borehole pressure monitoring. Time-lag and attenuation of the barometric signal that propagates into the EDZ have been measured at a metric scale. The identification of potential time-lag and attenuation variations needs further investigations, the long time series of borehole pressure monitoring shows pressure increase probably due to percolating water during successive snow cover and thawing periods as observed in the Roselend area during winter.

Antibacterial activity and mode of action of ε-polylysine against Escherichia coli O157:H7.

PubMed

Zhang, Xiaowei; Shi, Ce; Liu, Zuojia; Pan, Fengguang; Meng, Rizeng; Bu, Xiujuan; Xing, Heqin; Deng, Yanhong; Guo, Na; Yu, Lu

2018-04-10

Gram-negative Escherichia coli O157:H7 were chosen as model bacteria to evaluate the antimicrobial mechanism of ε-polylysine (ε-PL). The antibacterial activity of ε-PL was detected by measuring the minimum inhibitory concentration values as well as the time-kill curve. The membrane integrity was determined by ultraviolet (UV) absorption, membrane potential (MP) assay and flow cytometry (FCM) experiments. The permeability of the inner membrane was detected by β-galactosidase activity assay. Furthermore, electron microscopy [scanning electron microscopy (SEM) and transmission electron microscopy (TEM)] was utilized to observe bacterial morphology. These results demonstrated that ε-PL showed its antibacterial activity by changing the integrity and permeability of cell membranes, leading to rapid cell death. The electron microscopy analysis (SEM and TEM) results indicated that the bacterial cell morphology, membrane integrity and permeability were spoiled when the E. coli O157:H7 cells were exposed to minimum inhibitory concentrations of ε-PL (16 µg ml -1 ). In addition, the bacterial membrane was damaged more severely when the concentration of ε-PL was increased. The present study investigated the antimicrobial mechanism of ε-PL by measuring the content of cytoplasmic β-galactosidase, proteins and DNA. In addition, SEM and TEM were carried out to assess the mechanism. These results show that ε-PL has the ability to decrease the content of large molecules, cellular soluble proteins and nucleic acids associated with increasing the content of cytoplasmic β-galactosidase in supernatant by causing damage to the cell membranes. Consequently, the use of ε-PL as a natural antimicrobial agent should eventually become an appealing method in the field of food preservation.

Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

PubMed

Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

2018-01-15

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

PubMed

D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

2013-05-01

Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P < 0.001 in all cases). Circulating levels of pro-inflammatory cytokine TNF-α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

Fast therapeutic hypothermia prevents post-cardiac arrest syndrome through cyclophilin D-mediated mitochondrial permeability transition inhibition.

PubMed

Jahandiez, Vincent; Cour, Martin; Bochaton, Thomas; Abrial, Maryline; Loufouat, Joseph; Gharib, Abdallah; Varennes, Annie; Ovize, Michel; Argaud, Laurent

2017-07-01

The opening of the mitochondrial permeability transition pore (PTP), which is regulated by the matrix protein cyclophilin D (CypD), plays a key role in the pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated PTP inhibition in both heart and brain. In addition, we investigated whether specific pharmacological PTP inhibition would confer additive protection to cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by 120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group (CA only), hypothermia group (HT, hypothermia at 32-34 °C induced by external cooling at reperfusion), NIM group (injection at reperfusion of 2.5 mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following measurements were taken: hemodynamics, echocardiography, and cellular damage markers (including S100β protein and troponin Ic). Oxidative phosphorylation and PTP opening were assessed on mitochondria isolated from both brain and heart. Acetylation of CypD was measured by immunoprecipitation in both the cerebral cortex and myocardium. Hypothermia and NIM811 significantly prevented cardiovascular dysfunction, pupillary areflexia, and early tissue damage. Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening in both brain and heart mitochondria and prevented increase in CypD acetylation in brain. There were no additive beneficial effects in the combination of NIM811 and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post-CA syndrome by preventing mitochondrial permeability transition mainly through a CypD-dependent mechanism.

Role of the Fast Kinetics of Pyroglutamate-Modified Amyloid-β Oligomers in Membrane Binding and Membrane Permeability

PubMed Central

2015-01-01

Membrane permeability to ions and small molecules is believed to be a critical step in the pathology of Alzheimer’s disease (AD). Interactions of oligomers formed by amyloid-β (Aβ) peptides with the plasma cell membrane are believed to play a fundamental role in the processes leading to membrane permeability. Among the family of Aβs, pyroglutamate (pE)-modified Aβ peptides constitute the most abundant oligomeric species in the brains of AD patients. Although membrane permeability mechanisms have been studied for full-length Aβ1–40/42 peptides, these have not been sufficiently characterized for the more abundant AβpE3–42 fragment. Here we have compared the adsorbed and membrane-inserted oligomeric species of AβpE3–42 and Aβ1–42 peptides. We find lower concentrations and larger dimensions for both species of membrane-associated AβpE3–42 oligomers. The larger dimensions are attributed to the faster self-assembly kinetics of AβpE3–42, and the lower concentrations are attributed to weaker interactions with zwitterionic lipid headgroups. While adsorbed oligomers produced little or no significant membrane structural damage, increased membrane permeabilization to ionic species is understood in terms of enlarged membrane-inserted oligomers. Membrane-inserted AβpE3–42 oligomers were also found to modify the mechanical properties of the membrane. Taken together, our results suggest that membrane-inserted oligomers are the primary species responsible for membrane permeability. PMID:24950761

Permeability Variations Associated With Fault Reactivation in a Claystone Formation Investigated by Field Experiments and Numerical Simulations

NASA Astrophysics Data System (ADS)

Jeanne, Pierre; Guglielmi, Yves; Rutqvist, Jonny; Nussbaum, Christophe; Birkholzer, Jens

2018-02-01

We studied the relation between rupture and changes in permeability within a fault zone intersecting the Opalinus Clay formation at 300 m depth in the Mont Terri Underground Research Laboratory (Switzerland). A series of water injection experiments were performed in a borehole straddle interval set within the damage zone of the main fault. A three-component displacement sensor allowed an estimation of the displacement of a minor fault plane reactivated during a succession of step rate pressure tests. The experiment reveals that the fault hydromechanical (HM) behavior is different from one test to the other with varying pressure levels needed to trigger rupture and different slip behavior under similar pressure conditions. Numerical simulations were performed to better understand the reason for such different behavior and to investigate the relation between rupture nucleation, permeability change, pressure diffusion, and rupture propagation. Our main findings are as follows: (i) a rate frictional law and a rate-and-state permeability law can reproduce the first test, but it appears that the rate constitutive parameters must be pressure dependent to reproduce the complex HM behavior observed during the successive injection tests; (ii) almost similar ruptures can create or destroy the fluid diffusion pathways; (iii) a too high or too low diffusivity created by the main rupture prevents secondary rupture events from occurring whereas "intermediate" diffusivity favors the nucleation of a secondary rupture associated with the fluid diffusion. However, because rupture may in certain cases destroy permeability, this succession of ruptures may not necessarily create a continuous hydraulic pathway.

Numerical modeling of oil shale fragmentation experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuszmaul, J.S.

The economic development of modified in situ oil shale retorting will benefit from the ability to design a blasting scheme that creates a rubble bed of uniform permeability. Preparing such a design depends upon successfully predicting how a given explosive charge and firing sequence will fracture the oil shale. Numerical models are used to predict the extent of damage caused by a particular explosive charge. Recent single-blastwell cratering tests provided experimental measurements of the extent of damage induced by an explosion. Measuring rock damage involved crater excavation, rubble screening, crater elevation surveys, and posttest extraction of cores. These measurements weremore » compared to the damage calculated by the numerical model. Core analyses showed that the damage varied greatly from layer to layer. The numerical results also show this effect, indicating that rock damage is highly dependent on oil shale grade. The computer simulation also calculated particle velocities and dynamic stress amplitudes in the rock; predicted values agree with experimental measurements. Calculated rock fragmentation compared favorably with fragmentation measured by crater excavation and by core analysis. Because coring provides direct inspection of rock fragmentation, the use of posttest coring in future experiments is recommended.« less

Permeability evolution governed by shear: An example during spine extrusion at Unzen volcano, Japan

NASA Astrophysics Data System (ADS)

Ashworth, James; Lavallée, Yan; Wallace, Paul; Kendrick, Jackie; Coats, Rebecca; Miwa, Takahiro; Hess, Kai-Uwe

2017-04-01

A volcano's eruptive style is strongly controlled by the permeability of the magma and the surrounding edifice rock - explosive activity is more likely if exsolved gases cannot escape the system. In this study, we investigate how shear strain causes variations in permeability within a volcanic conduit, and discuss how spatio-temporal variation in shear regimes may develop. The eruption of Unzen volcano, Japan, which occurred between 1990 - 1995, culminated in the extrusion of a 60 metre-high dacitic spine. The spine, left exposed at the lava dome surface, displays the petrographic architecture of the magma in the shallow conduit. Observations and measurements made in the field are combined with laboratory experiments to understand the distribution of permeability in the shallow conduit. Examination of the lava dome led to the selection of two sites for detailed investigation. First, we examined a section of extruded spine 6 metres in width, which displays a transition from apparently unsheared rock in the conduit core to rocks exhibiting increasing shear towards the conduit margin, bounded by a fault gouge zone. Laboratory characterisation (mineralogy, porosity, permeability, X-ray tomography) was undertaken on these samples. In contrast, a second section of spine (extruded later during the eruption) exhibited a large tensile fracture, and this area was investigated using non-destructive in-situ permeability measurements. Our lab measurements show that in the first outcrop, permeability decreases across the shear zone from core to gouge by approximately one order of magnitude perpendicular to shear; a similar decrease is observed parallel to shear, but is less severe. The lowest permeability is observed in the most highly sheared block; here, permeability is 2.5 x10-14 m2 in the plane of shear and 9 x10-15 m2 perpendicular to shear. Our measurements clearly demonstrate the influence of shear on conduit permeability, with significant anisotropy in the shear zone. The sheared rocks are strongly micro-fractured, resulting in a porosity decrease of up to 4% and permeability decrease of over one order of magnitude with increasing effective pressure (effective pressure = confining pressure - pore pressure) between 5 - 100 MPa, representative of increasing lithostatic pressure from 200 m to 4 km depth in the crust. In contrast, our field study of the second spine section, which features a 2 cm wide by 3 metre-long tensile fracture flanked by a 40-cm wide shear damage zone, reveals that dilational shear can result in an increase in permeability of approximately three orders of magnitude. The contrasting shear zone characteristics can be attributed to different shear regimes, which likely occur at different depths in the conduit. At greater depth in the system, where lithostatic pressures largely exceed pore pressure, compactional shear appears to dominate, reducing the permeable porous network as magma strains along the conduit margin, whereas at shallower levels, where the effective pressure is low, dilational shear becomes dominant, resulting in the creation of permeable pathways. We conclude that contrasting shearing regimes may simultaneously affect magma ascent dynamics in volcanic conduits, causing a range of dynamic permeability variations (positive and negative), which dictate eruptive behaviour.

Soluble Tumor Necrosis Factor Alpha Promotes Retinal Ganglion Cell Death in Glaucoma via Calcium-Permeable AMPA Receptor Activation.

PubMed

Cueva Vargas, Jorge L; Osswald, Ingrid K; Unsain, Nicolas; Aurousseau, Mark R; Barker, Philip A; Bowie, Derek; Di Polo, Adriana

2015-09-02

Loss of vision in glaucoma results from the selective death of retinal ganglion cells (RGCs). Tumor necrosis factor α (TNFα) signaling has been linked to RGC damage, however, the mechanism by which TNFα promotes neuronal death remains poorly defined. Using an in vivo rat glaucoma model, we show that TNFα is upregulated by Müller cells and microglia/macrophages soon after induction of ocular hypertension. Administration of XPro1595, a selective inhibitor of soluble TNFα, effectively protects RGC soma and axons. Using cobalt permeability assays, we further demonstrate that endogenous soluble TNFα triggers the upregulation of Ca(2+)-permeable AMPA receptor (CP-AMPAR) expression in RGCs of glaucomatous eyes. CP-AMPAR activation is not caused by defects in GluA2 subunit mRNA editing, but rather reflects selective downregulation of GluA2 in neurons exposed to elevated eye pressure. Intraocular administration of selective CP-AMPAR blockers promotes robust RGC survival supporting a critical role for non-NMDA glutamate receptors in neuronal death. Our study identifies glia-derived soluble TNFα as a major inducer of RGC death through activation of CP-AMPARs, thereby establishing a novel link between neuroinflammation and cell loss in glaucoma. Tumor necrosis factor α (TNFα) has been implicated in retinal ganglion cell (RGC) death, but how TNFα exerts this effect is poorly understood. We report that ocular hypertension, a major risk factor in glaucoma, upregulates TNFα production by Müller cells and microglia. Inhibition of soluble TNFα using a dominant-negative strategy effectively promotes RGC survival. We find that TNFα stimulates the expression of calcium-permeable AMPA receptors (CP-AMPAR) in RGCs, a response that does not depend on abnormal GluA2 mRNA editing but on selective downregulation of the GluA2 subunit by these neurons. Consistent with this, CP-AMPAR blockers promote robust RGC survival supporting a critical role for non-NMDA glutamate receptors in glaucomatous damage. This study identifies a novel mechanism by which glia-derived soluble TNFα modulates neuronal death in glaucoma. Copyright © 2015 the authors 0270-6474/15/3512088-15$15.00/0.

Laboratory Permeability and Seismic velocity anisotropy measurements across the Alpine Fault, New Zealand

NASA Astrophysics Data System (ADS)

Faulkner, D.; Allen, M. J.; Tatham, D.; Mariani, E.; Boulton, C. J.

2015-12-01

The Alpine Fault, a transpressional plate boundary between the Australia-Pacific plates, is known to rupture periodically (200-400yr) with large magnitude earthquakes (Mw~8) and is currently nearing the end of its latest interseismic period. The hydraulic and elastic properties of fault zones influence the nature and style of earthquake rupture and associated processes; investigating these properties in Alpine Fault rocks yields insights into conditions late in the seismic cycle. We present a suite of laboratory permeability and P (Vp) and S (Vs) wave velocity measurements preformed on diverse fault rock lithologies recovered during the first phase of the Deep Fault Drilling Project (DFDP-1). DFDP-1 drilled two boreholes reaching depths of 100.6m and 151.4m and retrieved fault rocks from both the hanging wall and footwall, including ultramylonites, ultracomminuted gouges and variably foliated and unfoliated cataclasites. Drilling revealed a typical shallow fault structure: localised principal slip zones (PSZ) of gouge nested within a damage zone overprinted by a zone of alteration, a record of enhanced fluid-rock interaction. Core material was tested in three orthogonal directions, orientated relative to the down core axis and, when present, foliation. Measurements were conducted with pore pressure held at 5MPa over an effective pressure (Peff) range of 5-105MPa, equivalent to pressure conditions down to ~7km depth. Using the Pulse Transient technique permeabilities at Peff=5MPa range from 10-17 to 10-20m2, decreasing to 10-18 to 10-21m2 at Peff=105MPa. Vp and Vs decrease with increased proximity to the PSZ with Vp in the hanging wall spanning 4500-5900m/s, dropping to 3900-4200m/s at the PSZ and then increasing to 4400-5600m/s in the foot wall. Wave velocities and permeability are enhanced parallel to tectonic fabrics e.g. foliation defined by aligned phyllosillicates and quartz- feldspar clasts. These measurements constrain interseismic conditions within the Alpine Fault, a zone of damaged rock pervasively altered with phyllosilicates and carbonates.

[Study of changes in the enzyme-salt composition affecting the permeability of ocular tissues under infrasound phonophoresis].

PubMed

Filatov, V V

2005-01-01

This paper deals with the study of infrasound phonophoresis-induced changes in biochemical factors, which affect the permeability of eyeball tissues. During 10 days, the rabbit right eye was exposed to an infrasound in the changing pressure mode at 4 Hz and 173 dB for 10 minutes every day. The left eye remained control. After finishing a series of studies, the animals were slaughtered, the eyes were enucleated and prepared into individual tissues. Changes in sodium-potassium composition were investigated in the first series. By causing a reduction in the cellular content of K+, infrasound exposure was found to cause a decrease in membranous potential and activation Na-channel, as confirmed by the elevated intracellular levels of Na+. This in turn enhances ocular tissue permeability for drugs without damaging the structure of a cell membrane. Changes in the activity of the following enzymes: beta-glucosidase, cathepsin D, and hy- aluronidase. Infrasound was ascertained to enhance the activity of beta-glucosidase, which accounts for the lower levels of glucose in ocular tissues and points to the activation and acceleration of biochemical processes in the tissues. At the same time the increased concentrations of cathepsin D and hyaluronidase found in ocular tissues were responsible for a temporary reduction in the viscosity of hyaluronic acid, which promotes resolution of opacities, adhesions or scars and increased tissue permeability.

DaDyn-RS: a tool for the time-dependent simulation of damage, fluid pressure and long-term instability in alpine rock slopes

NASA Astrophysics Data System (ADS)

Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

2017-04-01

Large mountain slopes in alpine environments undergo a complex long-term evolution from glacial to postglacial environments, through a transient period of paraglacial readjustment. During and after this transition, the interplay among rock strength, topographic relief, and morpho-climatic drivers varying in space and time can lead to the development of different types of slope instability, from sudden catastrophic failures to large, slow, long-lasting yet potentially catastrophic rockslides. Understanding the long-term evolution of large rock slopes requires accounting for the time-dependence of deglaciation unloading, permeability and fluid pressure distribution, displacements and failure mechanisms. In turn, this is related to a convincing description of rock mass damage processes and to their transition from a sub-critical (progressive failure) to a critical (catastrophic failure) character. Although mechanisms of damage occurrence in rocks have been extensively studied in the laboratory, the description of time-dependent damage under gravitational load and variable external actions remains difficult. In this perspective, starting from a time-dependent model conceived for laboratory rock deformation, we developed Dadyn-RS, a tool to simulate the long-term evolution of real, large rock slopes. Dadyn-RS is a 2D, FEM model programmed in Matlab, which combines damage and time-to-failure laws to reproduce both diffused damage and strain localization meanwhile tracking long-term slope displacements from primary to tertiary creep stages. We implemented in the model the ability to account for rock mass heterogeneity and property upscaling, time-dependent deglaciation, as well as damage-dependent fluid pressure occurrence and stress corrosion. We first tested DaDyn-RS performance on synthetic case studies, to investigate the effect of the different model parameters on the mechanisms and timing of long-term slope behavior. The model reproduces complex interactions between topography, deglaciation rate, mechanical properties and fluid pressure occurrence, resulting in different kinematics, damage patterns and timing of slope instabilities. We assessed the role of groundwater on slope damage and deformation mechanisms by introducing time-dependent pressure cycling within simulations. Then, we applied DaDyn-RS to real slopes located in the Italian Central Alps, affected by an active rockslide and a Deep Seated Gravitational Slope Deformation, respectively. From Last Glacial Maximum to present conditions, our model allows reproducing in an explicitly time-dependent framework the progressive development of damage-induced permeability, strain localization and shear band differentiation at different times between the Lateglacial period and the Mid-Holocene climatic transition. Different mechanisms and timings characterize different styles of slope deformations, consistently with available dating constraints. DaDyn-RS is able to account for different long-term slope dynamics, from slow creep to the delayed transition to fast-moving rockslides.

Edaravone Protects against Methylglyoxal-Induced Barrier Damage in Human Brain Endothelial Cells

PubMed Central

Tóth, Andrea E.; Walter, Fruzsina R.; Bocsik, Alexandra; Sántha, Petra; Veszelka, Szilvia; Nagy, Lajos; Puskás, László G.; Couraud, Pierre-Olivier; Takata, Fuyuko; Dohgu, Shinya; Kataoka, Yasufumi; Deli, Mária A.

2014-01-01

Background Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. PMID:25033388

Ascorbic Acid Repletion: A Possible Therapy for Diabetic Macular Edema?

PubMed Central

May, James M.

2016-01-01

Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-κB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. PMID:26898503

Vitamin E protects against the mitochondrial damage caused by cyclosporin A in LLC-PK1 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arriba, G. de; Seccion de Nefrologia del Hospital Universitario de Guadalajara; Departamento de Medicina de la Universidad de Alcala de Henares

Cyclosporin A (CsA) has nephrotoxic effects known to involve reactive oxygen species (ROS), since antioxidants prevent the kidney damage induced by this drug. Given that mitochondria are among the main sources of intracellular ROS, the aims of our study were to examine the mitochondrial effects of CsA in the porcine renal endothelial cell line LLC-PK1 and the influence of the antioxidant Vitamin E (Vit E). Following the treatment of LLC-PK1 cells with CsA, we assessed the mitochondrial synthesis of superoxide anion, permeability transition pore opening, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome c release and cellular apoptosis, using flow cytometry andmore » confocal microscopy procedures. Similar experiments were done after Vit E preincubation of cells. CsA treatment increased superoxide anion in a dose-dependent way. CsA opened the permeability transition pores, caused Bax migration to mitochondria, and decreased mitochondrial membrane potential and cardiolipin content. Also CsA released cytochrome c into cytosol and provoked cellular apoptosis. Vit E pretreatment inhibited the effects that CsA induced on mitochondrial structure and function in LLC-PK1 cells and avoided apoptosis. CsA modifies mitochondrial LLC-PK1 cell physiology with loss of negative electrochemical gradient across the inner mitochondrial membrane and increased lipid peroxidation. These features are related to apoptosis and can explain the cellular damage that CsA induces. As Vit E inhibited these effects, our results suggest that they were mediated by an increase in ROS production by mitochondria.« less

Damage of Escherichia coli membrane by bactericidal agent polyhexamethylene guanidine hydrochloride: micrographic evidences.

PubMed

Zhou, Z X; Wei, D F; Guan, Y; Zheng, A N; Zhong, J J

2010-03-01

The purpose of this study was to provide micrographic evidences for the damaged membrane structure and intracellular structure change of Escherichia coli strain 8099, induced by polyhexamethylene guanidine hydrochloride (PHMG). The bactericidal effect of PHMG on E. coli was investigated based on beta-galactosidase activity assay, fluorescein-5-isothiocyanate confocal laser scanning microscopy, field emission scanning electron microscopy and transmission electron microscopy. The results revealed that a low dose (13 microg ml(-1)) of PHMG slightly damaged the outer membrane structure of the treated bacteria and increased the permeability of the cytoplasmic membrane, while no significant damage was observed to the morphological structure of the cells. A high dose (23 microg ml(-1)) of PHMG collapsed the outer membrane structure, led to the formation of a local membrane pore across the membrane and badly damaged the internal structure of the cells. Subsequently, intracellular components were leaked followed by cell inactivation. Dose-dependent membrane disruption was the main bactericidal mechanism of PHMG. The formation of the local membrane pores was probable after exposure to a high dose (23 microg ml(-1)) of PHMG. Micrographic evidences were provided about the damaged membrane structure and intracellular structure change of E. coli. The presented information helps understand the bactericidal mechanism of PHMG by membrane damage.

Application of acoustic emission to the study of microfissure damage to composites used in the aeronautic and space industries

NASA Astrophysics Data System (ADS)

Perami, R.; Grezes-Besset, R.; Prince, W.

The use of AE to study microcracking in hybrid glass-carbon and kevlar laminates relevant to the aerospace industry was experimentally studied. It was found that some plastics reinforced by high-modulus fibers are especially prone to progressive cracking. The use of AE and permeability variations to analyze cracking under loads, fatigue, and aging of the composites is shown.

Apparatus and method for simulating material damage from a fusion reactor

DOEpatents

Smith, Dale L.; Greenwood, Lawrence R.; Loomis, Benny A.

1989-01-01

An apparatus and method for simulating a fusion environment on a first wall or blanket structure. A material test specimen is contained in a capsule made of a material having a low hydrogen solubility and permeability. The capsule is partially filled with a lithium solution, such that the test specimen is encapsulated by the lithium. The capsule is irradiated by a fast fission neutron source.

Apparatus and method for simulating material damage from a fusion reactor

DOEpatents

Smith, D.L.; Greenwood, L.R.; Loomis, B.A.

1988-05-20

This paper discusses an apparatus and method for simulating a fusion environment on a first wall or blanket structure. A material test specimen is contained in a capsule made of a material having a low hydrogen solubility and permeability. The capsule is partially filled with a lithium solution, such that the test specimen is encapsulated by the lithium. The capsule is irradiated by a fast fission neutron source.

Apparatus and method for simulating material damage from a fusion reactor

DOEpatents

Smith, Dale L.; Greenwood, Lawrence R.; Loomis, Benny A.

1989-03-07

An apparatus and method for simulating a fusion environment on a first wall or blanket structure. A material test specimen is contained in a capsule made of a material having a low hydrogen solubility and permeability. The capsule is partially filled with a lithium solution, such that the test specimen is encapsulated by the lithium. The capsule is irradiated by a fast fission neutron source.

Neuroprotection of brain-permeable iron chelator VK-28 against intracerebral hemorrhage in mice.

PubMed

Li, Qian; Wan, Jieru; Lan, Xi; Han, Xiaoning; Wang, Zhongyu; Wang, Jian

2017-09-01

Iron overload plays a key role in the secondary brain damage that develops after intracerebral hemorrhage (ICH). The significant increase in iron deposition is associated with the generation of reactive oxygen species (ROS), which leads to oxidative brain damage. In this study, we examined the protective effects of VK-28, a brain-permeable iron chelator, against hemoglobin toxicity in an ex vivo organotypic hippocampal slice culture (OHSC) model and in middle-aged mice subjected to an in vivo, collagenase-induced ICH model. We found that the effects of VK-28 were similar to those of deferoxamine (DFX), a well-studied iron chelator. Both decreased cell death and ROS production in OHSCs and in vivo, decreased iron-deposition and microglial activation around hematoma in vivo, and improved neurologic function. Moreover, compared with DFX, VK-28 polarized microglia to an M2-like phenotype, reduced brain water content, deceased white matter injury, improved neurobehavioral performance, and reduced overall death rate after ICH. The protection of VK-28 was confirmed in a blood-injection ICH model and in aged-male and young female mice. Our findings indicate that VK-28 is protective against iron toxicity after ICH and that, at the dosage tested, it has better efficacy and less toxicity than DFX does.

UVA Irradiation of Dysplastic Keratinocytes: Oxidative Damage versus Antioxidant Defense

PubMed Central

Nechifor, Marina T.; Niculiţe, Cristina M.; Urs, Andreea O.; Regalia, Teodor; Mocanu, Mihaela; Popescu, Alexandra; Manda, Gina; Dinu, Diana; Leabu, Mircea

2012-01-01

UVA affects epidermal cell physiology in a complex manner, but the harmful effects have been studied mainly in terms of DNA damage, mutagenesis and carcinogenesis. We investigated UVA effects on membrane integrity and antioxidant defense of dysplastic keratinocytes after one and two hours of irradiation, both immediately after exposure, and 24 h post-irradiation. To determine the UVA oxidative stress on cell membrane, lipid peroxidation was correlated with changes in fatty acid levels. Membrane permeability and integrity were assessed by propidium iodide staining and lactate dehydrogenase release. The effects on keratinocyte antioxidant protection were investigated in terms of catalase activity and expression. Lipid peroxidation increased in an exposure time-dependent manner. UVA exposure decreased the level of polyunsaturated fatty acids, which gradually returned to its initial value. Lactate dehydrogenase release showed a dramatic loss in membrane integrity after 2 h minimum of exposure. The cell ability to restore membrane permeability was noted at 24 h post-irradiation (for one hour exposure). Catalase activity decreased in an exposure time-dependent manner. UVA-irradiated dysplastic keratinocytes developed mechanisms leading to cell protection and survival, following a non-lethal exposure. The surviving cells gained an increased resistance to apoptosis, suggesting that their pre-malignant status harbors an abnormal ability to control their fate. PMID:23222638

Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

PubMed

Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

2016-03-15

Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Dehydration rate determines the degree of membrane damage and desiccation tolerance in bryophytes.

PubMed

Cruz de Carvalho, Ricardo; Catalá, Myriam; Branquinho, Cristina; Marques da Silva, Jorge; Barreno, Eva

2017-03-01

Desiccation tolerant (DT) organisms are able to withstand an extended loss of body water and rapidly resume metabolism upon rehydration. This ability, however, is strongly dependent on a slow dehydration rate. Fast dehydration affects membrane integrity leading to intracellular solute leakage upon rehydration and thereby impairs metabolism recovery. We test the hypothesis that the increased cell membrane damage and membrane permeability observed under fast dehydration, compared with slow dehydration, is related to an increase in lipid peroxidation. Our results reject this hypothesis because following rehydration lipid peroxidation remains unaltered, a fact that could be due to the high increase of NO upon rehydration. However, in fast-dried samples we found a strong signal of red autofluorescence upon rehydration, which correlates with an increase in ROS production and with membrane leakage, particularly the case of phenolics. This could be used as a bioindicator of oxidative stress and membrane damage. © 2016 Scandinavian Plant Physiology Society.

Inhalation health effects of fine particles from the co-combustion of coal and refuse derived fuel.

PubMed

Fernandez, Art; Wendt, Jost O L; Wolski, Natacha; Hein, Klaus R G; Wang, Shengjun; Witten, Mark L

2003-06-01

This paper is concerned with health effects from the inhalation of particulate matter (PM) emitted from the combustion of coal, and from the co-combustion of refuse derived fuel (RDF) and pulverized coal mixtures, under both normal and low NO(x) conditions. Specific issues focus on whether the addition of RDF to coal has an effect on PM toxicity, and whether the application of staged combustion (for low NO(x)) may also be a factor in this regard. Ash particles were sampled and collected from a pilot scale combustion unit and then re-suspended and diluted to concentrations of approximately 1000 microg/m(3). These particles were inhaled by mice, which were held in a nose-only exposure configuration. Exposure tests were for 1 h per day, and involved three sets (eight mice per set) of mice. These three sets were exposed over 8, 16, and 24 consecutive days, respectively. Pathological lung damage was measured in terms of increases in lung permeability. Results show that the re-suspended coal/RDF ash appeared to cause very different effects on lung permeability than did coal ash alone. In addition, it was also shown that a "snapshot" of lung properties after a fixed number of daily 1-h exposures, can be misleading, since apparent repair mechanisms cause lung properties to change over a period of time. For the coal/RDF, the greatest lung damage (in terms of lung permeability increase) occurred at the short exposure period of 8 days, and thereafter appeared to be gradually repaired. Ash from staged (low NO(x)) combustion of coal/RDF appeared to cause greater lung injury than that from unstaged (high NO(x)) coal/RDF combustion, although the temporal behavior and (apparent) repair processes in each case were similar. In contrast to this, coal ash alone showed a slight decrease of lung permeability after 1 and 3 days, and this disappeared after 12 days. These observations are interpreted in the light of mechanisms proposed in the literature. The results all suggest that the composition of particles actually inhaled is important in determining lung injury. Particle size segregated leachability measurements showed that water soluble sulfur, zinc, and vanadium, but not iron, were present in the coal/RDF ash particles, which caused lung permeabilities to increase. However, the differences in health effects between unstaged and staged coal/RDF combustion could not be attributed to variations in pH values of the leachate.

Deep permeability of the San Andreas Fault from San Andreas Fault Observatory at Depth (SAFOD) core samples

USGS Publications Warehouse

Morrow, Carolyn A.; Lockner, David A.; Moore, Diane E.; Hickman, Stephen H.

2014-01-01

The San Andreas Fault Observatory at Depth (SAFOD) scientific borehole near Parkfield, California crosses two actively creeping shear zones at a depth of 2.7 km. Core samples retrieved from these active strands consist of a foliated, Mg-clay-rich gouge containing porphyroclasts of serpentinite and sedimentary rock. The adjacent damage zone and country rocks are comprised of variably deformed, fine-grained sandstones, siltstones, and mudstones. We conducted laboratory tests to measure the permeability of representative samples from each structural unit at effective confining pressures, Pe up to the maximum estimated in situ Pe of 120 MPa. Permeability values of intact samples adjacent to the creeping strands ranged from 10−18 to 10−21 m2 at Pe = 10 MPa and decreased with applied confining pressure to 10−20–10−22 m2 at 120 MPa. Values for intact foliated gouge samples (10−21–6 × 10−23 m2 over the same pressure range) were distinctly lower than those for the surrounding rocks due to their fine-grained, clay-rich character. Permeability of both intact and crushed-and-sieved foliated gouge measured during shearing at Pe ≥ 70 MPa ranged from 2 to 4 × 10−22 m2 in the direction perpendicular to shearing and was largely insensitive to shear displacement out to a maximum displacement of 10 mm. The weak, actively-deforming foliated gouge zones have ultra-low permeability, making the active strands of the San Andreas Fault effective barriers to cross-fault fluid flow. The low matrix permeability of the San Andreas Fault creeping zones and adjacent rock combined with observations of abundant fractures in the core over a range of scales suggests that fluid flow outside of the actively-deforming gouge zones is probably fracture dominated.

Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

PubMed Central

Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

1983-01-01

We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases in the level of colicin. Within an hour after induction more than 90% of cells carrying cea+kil+ plasmids are killed and macromolecular synthesis stops, capacity for transport of proline, thiomethyl β-D-galactoside, and α-methyl glucoside is lost, and the membrane becomes abnormally permeable as indicated by an increased accessibility of intracellular β-galactosidase to the substrate o-nitrophenyl β-D-galactoside. All of these events occur when a cea-kil+imm+ plasmid is present and none does when the plasmid is cea+kil-imm+, so the damage can be attributed solely to the Kil function and not to the presence of colicin. However, cells carrying a cea+kil-imm- plasmid are killed upon induction, apparently by action of endogenous colicin on the nonimmune cytoplasmic membrane. The pattern of accompanying physiological damage is distinguished from the kil+-associated damage by an enhancement of α-methyl glucoside uptake and accumulation and efflux of α-methyl glucoside 6-phosphate and by an absence of the alteration in membrane permeability for o-nitrophenyl β-D-galactoside. These features are typical of colicin E1 action on the membrane. The induced damage is not prevented by trypsin and occurs in cells of a strain specifically tolerant to exogenous colicin E1, indicating that the attack is from inside the cell. PMID:6403939

Effects of metformin treatment on glioma-induced brain edema

PubMed Central

Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

2016-01-01

Considerable evidence has demonstrated that metformin can activate 5’-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo. PMID:27648126

Effects of metformin treatment on glioma-induced brain edema.

PubMed

Zhao, Bin; Wang, Xiaoke; Zheng, Jun; Wang, Hailiang; Liu, Jun

2016-01-01

Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2. However, 0.5 mM metformin treatment protected bEnd3 endothelial cell monolayer from hypoxia or VEGF-induced permeability, which was correlated with increased expression of tight junction proteins. Furthermore, metformin treatment attenuated AQP4 protein expression in cultured astrocytes. Such an effect involved the activation of AMPK and inhibition of NF-κB. Finally, metformin treatment dose-dependently reduced glioma induced vascular permeability and cerebral edema in vivo in rats. Thus, our results suggested that metformin may protect endothelial cell tight junction, prevent damage to the blood brain barrier induced by brain tumor growth, and alleviate the formation of cerebral edema. Furthermore, since the formation of cytotoxic edema and AQP4 expression was positively correlated, our results indicated that metformin may reduce the formation of cytotoxic edema. However, given that AQP4 plays a key role in the elimination of cerebral edema, attenuation of AQP4 expression by metformin may reduce the elimination of cerebral edema. Hence, future studies will be necessary to dissect the specific mechanisms of metformin underlying the dynamics of tumor-induced brain edema in vivo.

Bacterial DNA induces pulmonary damage via TLR-9 through cross-talk with neutrophils.

PubMed

Itagaki, Kiyoshi; Adibnia, Yasaman; Sun, Shiqin; Zhao, Cong; Sursal, Tolga; Chen, Yu; Junger, Wolfgang; Hauser, Carl J

2011-12-01

Bacterial DNA (bDNA) contains hypomethylated "CpG" repeats that can be recognized by Toll-like receptor 9 (TLR-9) as a pathogen-associated molecular pattern. The ability of bDNA to initiate lung injury via TLR-9 has been inferred on the basis of studies using artificial CpG DNA. But the role of authentic bDNA in lung injury is still unknown. Moreover, the mechanisms by which CpG DNA species can lead to pulmonary injury are unknown, although neutrophils (PMNs) are thought to play a key role in the genesis of septic acute lung injury. We evaluated the effects of bDNA on PMN-endothelial cell (EC) interactions thought critical for initiation of acute lung injury. Using a biocapacitance system to monitor real-time changes in endothelial permeability, we demonstrate here that bDNA causes EC permeability in a dose-dependent manner uniquely in the presence of PMNs. These permeability changes are inhibited by chloroquine, suggesting TLR-9 dependency. When PMNs were preincubated with bDNA and applied to ECs or when bDNA was applied to ECs without PMNs, no permeability changes were detected. To study the underlying mechanisms, we evaluated the effects of bDNA on PMN-EC adherence. Bacterial DNA significantly increased PMN adherence to ECs in association with upregulated adhesion molecules in both cell types. Taken together, our results strongly support the conclusion that bDNA can initiate lung injury by stimulating PMN-EC adhesive interactions predisposing to endothelial permeability. Bacterial DNA stimulation of TLR-9 appears to promote enhanced gene expression of adhesion molecules in both cell types. This leads to PMN-EC cross-talk, which is required for injury to occur.

Dietary management of acute diarrhoea in children: effect of fermented and amylase-digested weaning foods on intestinal permeability.

PubMed

Willumsen, J F; Darling, J C; Kitundu, J A; Kingamkono, R R; Msengi, A E; Mduma, B; Sullivan, K R; Tomkins, A M

1997-03-01

There is a strong relationship between diarrhoea, malnutrition, and intestinal integrity. To investigate the effect of different dietary-treatment on intestinal permeability during acute diarrhoea, 87 Tanzanian children aged 6-25 months were recruited to this study when admitted to hospital. Children with acute diarrhoea were rehydrated and then randomly assigned to one of three dietary treatment groups: a conventional low-energy density porridge, a high-energy density amylase digested porridge (AMD), or a high-energy density amylase digested and then fermented porridge (FAD). Lactulose/mannitol permeability tests were performed on admission, at 3 days, and at follow-up 2 and 4 weeks after discharge. The lactulose/mannitol (L/M) ratios were compared between dietary treatment groups and to a group of age-matched, healthy control subjects. Children with diarrhoea had higher L/M ratios (geometric mean 0.85, 95% CI 0.68-1.05) compared with control subjects (0.14, 0.12-0.17) on admission. There was a significant difference in the change in L/M ratio between admission and 3 days between dietary treatment groups in favour of the FAD group (p < 0.05). Dietary treatment and intestinal damage at admission explain 13.5% of the variation in L/M ratio, but when age at admission and age at weaning are included as covariants, 21.9% is explained. FAD porridge seems to be more effective in the treatment of intestinal permeability than AMD or conventional porridge. Urinary lactose concentrations in spot urine samples taken prior to the permeability test were also measured. There was a significant correlation with the L/M ratio (correlation coefficient = 0.62, p < 0.001).

Acute exercises induce disorders of the gastrointestinal integrity in a murine model.

PubMed

Gutekunst, Katrin; Krüger, Karsten; August, Christian; Diener, Martin; Mooren, Frank-Christoph

2014-03-01

Many endurance athletes complain about gastrointestinal (GI) symptoms. It is assumed that exercise-induced shift of perfusion with consecutive hypoperfusion of the enteral vascular system leads to an increased GI permeability and tissue damage. Therefore, the aim of the study was to investigate permeability, apoptosis, electrogenic ion transport (Isc), and tissue conductance (Gt) of the small intestine in a murine exercise model. After spirometry, male Swiss CD-1 mice were subjected to an intensive treadmill exercise (80% VO2max). Sedentary mice served as controls. The small intestine was removed at several time intervals post-exercise. Apoptotic cells were determined by the TUNEL method, while fluorescein isothiocyanate dextran permeation indicated intestinal permeability. The Gt and Isc measurements were carried out in a modified Ussing chamber. Apoptosis of epithelial cells increased continuously until 24 h post exercise (0.8 ± 0.42 versus 39.2 ± 26.0%; p < 0.05). Compared with the control group the permeability increased 2 h after exercise (0.47 ± 0.07 versus 0.67 ± 0.14 FU/min; p < 0.05). Isc measurements of the ileum were augmented after 24 h (3.33 ± 0.56 versus 5.77 ± 1.16 μEq/h/cm(2); p < 0.05). At this time the Gt increased as well (28.8 ± 3.37 versus 32.5 ± 2.59 mS/cm(2); p < 0.05). In the murine exercise model there is evidence that after intense endurance exercise repair processes occur in small intestinal epithelial cells, which affect permeability, Gt, and Isc. The formation of lamellipodia to close the "leaky" tight junctions caused by apoptosis might be an underlying mechanism.

Glutamine Supplementation Attenuates Ethanol-Induced Disruption of Apical Junctional Complexes in Colonic Epithelium and Ameliorates Gut Barrier Dysfunction and Fatty Liver in Mice

PubMed Central

Chaudhry, Kamaljit K.; Shukla, Pradeep K.; Mir, Hina; Manda, Bhargavi; Gangwar, Ruchika; Yadav, Nikki; McMullen, Megan; Nagy, Laura E.; Rao, RadhaKrishna

2015-01-01

Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of glutamine in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed Gln-free diet and absent in mice fed Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. PMID:26365579

Segmental microvascular permeability in ischemia-reperfusion injury in rat lung.

PubMed

Khimenko, P L; Taylor, A E

1999-06-01

Segmental microvascular permeabilities were measured using pre- and postalveolar vessel capillary filtration coefficient (Kfc) values (ml. min-1. cmH2O-1. 100 g-1) in isolated rat lungs subjected to ischemia-reperfusion (I/R). Total Kfc values measured in flowing and nonflowing lungs were highly correlated (r = 0.98, P < 0.0001). Kfc values were then measured in another group of lungs under no-flow conditions when airway pressure was increased to 20 cmH2O and either the arterial or venous pressure was elevated to 7-8 cmH2O to measure the prealveolar and postalveolar Kfc values. Control total and postalveolar Kfc values were 0.0225 +/- 0.001 and 0.0219 +/- 0.001 ml. min-1. cmH2O-1. 100 g-1, respectively, and the prealveolar permeability was extremely small (0.00003 +/- 0.00005 ml. min-1. cmH2O-1. 100 g-1). Kfc values were again made in nonflowing lungs that had been subjected to 45 min of ischemia followed by 30 min of reperfusion. After I/R, the total membrane Kfc increased 10-fold to 0.2597 +/- 0.006 ml. min-1. cmH2O-1. 100 g-1, the prealveolar Kfc increased to 0.0677 +/- 0.003 ml. min-1. cmH2O-1. 100 g-1, and the postalveolar Kfc increased to 0.1354 +/- 0.008 ml. min-1. cmH2O-1. 100 g-1 (P < 0.05 for all I/R values). These data indicate that normal solvent microvascular permeability was predominantly postalveolar, and after I/R damage, the postalveolar (venular) permeability comprised 52% of the total, whereas the prealveolar and alveolar vessels comprised only 27 and 23%, respectively, of the total Kfc.

In the absence of overt urothelial damage, chondroitinase ABC digestion of the GAG layer increases bladder permeability in ovariectomized female rats

PubMed Central

Van Gordon, Samuel; Tyler, Karl; Kropp, Bradley; Towner, Rheal; Lin, HsuehKung; Marentette, John O.; McHowat, Jane; Mohammedi, Ehsan; Greenwood-Van Meerveld, Beverley

2016-01-01

Loss of integrity of the protective impermeability barrier in the urothelium has been identified as significant in bladder dysfunction. In this study, we tested the theory that the luminal layer of glycosaminoglycans (GAG) serves as an important component of barrier function. The peptide polycation protamine sulfate (PS), 1 mg/ml, was instilled intravesically for 10 min into rat bladders. Chondroitinase ABC (ChABC), 63 IU/ml, was instilled into an additional six rats for 30 min to digest the GAG layer. Unmanipulated controls and sham-injected controls were also performed. After 24 h, the rats were euthanized, the bladders were removed, and permeability was assessed in the Ussing chamber and by diffusion of FITC-labeled dextran (4 kDa) to measure macromolecular permeability. The status of tight junctions was assessed by immunofluorescence and electron microscopy. In control and sham treated rat bladders, the transepithelial electrical resistance were means of 2.5 ± 1.1 vs. 2.6 ± 1.1 vs 1.2 ± 0.5 and 1.01 ± 0.7 kΩ·cm2 in the PS-treated and ChABC-treated rat bladders (P = 0.0016 and P = 0.0039, respectively). Similar differences were seen in dextran permeability. Histopathology showed a mild inflammation following PS treatment, but the ChABC-treated bladders were indistinguishable from controls. Tight junctions generally remained intact. ChABC digestion alone induced bladder permeability, confirming the importance of the GAG layer to bladder barrier function and supports that loss of the GAG layer seen in bladder biopsies of interstitial cystitis patients could be a significant factor producing symptoms for at least some interstitial cystitis/painful bladder syndrome patients. PMID:26911855

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus

PubMed Central

Chen, Xiaodi; Threlkeld, Steven W.; Cummings, Erin E.; Juan, Ilona; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Sadowska, Grazyna B.; Stonestreet, Barbara S.

2012-01-01

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days-of-gestation without ischemia, and 4-, 24-, or 48-h after ischemia. The largest increase in Ki (P<0.05) was 4-h after ischemia. Occludin and claudin-5 expressions decreased at 4-h, but returned toward control levels 24- and 48-h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4-h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24- and 48- than 4-h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. PMID:22986172

New Laboratory Observations of Thermal Pressurization Weakening

NASA Astrophysics Data System (ADS)

Badt, N.; Tullis, T. E.; Hirth, G.

2017-12-01

Dynamic frictional weakening due to pore fluid thermal pressurization has been studied under elevated confining pressure in the laboratory, using a rotary-shear apparatus having a sample with independent pore pressure and confining pressure systems. Thermal pressurization is directly controlled by the permeability of the rocks, not only for the initiation of high-speed frictional weakening but also for a subsequent sequence of high-speed sliding events. First, the permeability is evaluated at different effective pressures using a method where the pore pressure drop and the flow-through rate are compared using Darcy's Law as well as a pore fluid oscillation method, the latter method also permitting measurement of the storage capacity. Then, the samples undergo a series of high-speed frictional sliding segments at a velocity of 2.5 mm/s, under an applied confining pressure and normal stress of 45 MPa and 50 MPa, respectively, and an initial pore pressure of 25 MPa. Finally the rock permeability and storage capacity are measured again to assess the evolution of the rock's pore fluid properties. For samples with a permeability of 10-20 m2 thermal pressurization promotes a 40% decrease in strength. However, after a sequence of three high-speed sliding events, the magnitude of weakening diminishes progressively from 40% to 15%. The weakening events coincide with dilation of the sliding interface. Moreover, the decrease in the weakening degree with progressive fast-slip events suggest that the hydraulic diffusivity may increase locally near the sliding interface during thermal pressurization-enhanced slip. This could result from stress- or thermally-induced damage to the host rock, which would perhaps increase both permeability and storage capacity, and so possibly decrease the susceptibility of dynamic weakening due to thermal pressurization in subsequent high-speed sliding events.

Cyclosporin A inhibits UV-radiation-induced membrane damage but is unable to inhibit carboxyatractyloside-induced permeability transition.

PubMed

García, Noemí; Zazueta, Cecilia; El-Hafidi, Mohammed; Pavón, Natalia; Martínez-Abundis, Eduardo; Hernández-Esquivel, Luz; Chávez, Edmundo

2009-11-01

This work was undertaken to gain further information on the chemical characteristics of the membrane entity involved in the formation of the nonspecific pore. Mitochondria were subjected to oxidative stress by exposure to UV radiation. The results indicate that ultraviolet C radiation induces structural modifications in the adenine nucleotide translocase that lead to membrane permeability transition. Membrane leakage was assessed by measuring mitochondrial Ca2+ transport, the transmembrane electric gradient, and mitochondrial swelling. UV-irradiated mitochondria were unable to retain matrix Ca2+ or to maintain a high level of membrane potential when Ca2+ was added; furthermore, UV-irradiated mitochondria underwent large amplitude swelling. Release of cytochrome c and formation of malondialdehyde, owing to lipid peroxidation, were also seen. Structural modifications of the translocase were revealed by an increase in the binding of the fluorescent probe eosin-5-maleimide to thiol residues of the ADP/ATP carrier. These modifications, taken together with findings indicating that cyclosporin resulted unable to inhibit carboxyatractyloside-induced permeability transition, prompted us to conclude that the translocase could constitute the nonspecific pore or at least be an important modulator of it.

In Vitro Studies of Primary Explosive Blast Loading on Neurons

DTIC Science & Technology

2015-09-01

blast but was significantly higher for the triple blast. Membrane permeability was also evaluated by calcein dye . Calcein is normally a membrane...impermeable dye ; however, upon damage to the plasma membrane, leakage of the dye into the cytosol can occur, causing an increase in the fluorescence of the...intensities were significantly higher for the injured cells compared with the control and sham. However, the difference in dye uptake between the singly and

Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical characterisation and permeability through Caco-2 cell monolayers.

PubMed

Hafner, Anita; Lovrić, Jasmina; Voinovich, Dario; Filipović-Grcić, Jelena

2009-11-03

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was investigated. The size, zeta potential and melatonin loading of the lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid S45, S75 and S100) and chitosan content in the preparation. The NPs were characterised by mean diameter and zeta potential ranging between 121.6 and 347.5 nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative charge and chitosan content in the preparation. Melatonin loadings were up to 7.1%. All NPs were characterised by prolonged release profiles with an initial burst (approximately 25%), followed by a slow release phase. Approximately 60-70% of melatonin was released in 4h. The permeability of melatonin was investigated using Caco-2 cells as an in vitro model of the epithelial barrier. Melatonin permeability from an NP suspension prepared with Lipoid S45 lecithin and a lecithin-to-chitosan weight ratio (L/C) of 20:1 (sample C2) was significantly improved compared to the permeability of melatonin from the solution (P<0.001) and from all other NPs investigated (P<0.05). The results obtained by the cell viability studies (MTT and LDH leakage assays) showed that C2 NP suspension did not induce plasma membrane damage or decrease cell viability and could be safely applied to Caco-2 cells in the concentration range tested (<400 microg/ml).

Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

PubMed

Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

2016-11-01

Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine-supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

How can fluid overpressures be developed and maintained in crustal fault zones ?

NASA Astrophysics Data System (ADS)

LECLÈRE, H.; Cappa, F.; Faulkner, D. R.; Armitage, P. J.; Blake, O. O.; Fabbri, O.

2013-12-01

The presence of fluid overpressure in crustal fault zones is known to play a key role on the stability of faults and it has often been invoked to explain the triggering of earthquakes and the apparent weakness of misoriented faults. However, the mechanisms allowing the development and maintenance of fluid overpressures in fault remain unresolved. We investigate how fluid overpressures can be developed and maintained in complex fault zones with hydraulic and elastic heterogeneities. Here we address this question combining geological observations, laboratory experiments and hydromechanical models of an active crustal fault zone in the Ubaye-Argentera area (southeastern France). The fault zone studied is located in the Argentera external crystalline massif and is connected to regional NW-SE steeply-dipping dextral strike-slip faults with an offset of several kilometers. The fault zone cuts through migmatitic gneisses composed of quartz, K-feldspar, plagioclase, biotite and muscovite. It exposes several anastomosing core zones surrounded by damage zones with a pluri-decametric total width. The core zones are made up of centimetric to pluridecimetric phyllosilicate-rich gouge layers while the damage zones are composed of pluri-metric phyllonitic rock derived from mylonite. The determination of fault structure in the field and its hydraulic and mechanical properties in the lab are key aspects to improve our understanding of the role of fluids in fault mechanics and earthquake triggering. Here, the permeability and elastic moduli of the host rock, damage zone and fault core were measured from natural plugs with a diameter of 20 mm and lengths between 26 to 51 mm, using a high-pressure hydrostatic fluid-flow apparatus. Measurements were made with confining pressures ranging from 30 to 210 MPa and using argon pore fluid pressure of 20 MPa. Data show a reduction of the permeability values of one order of magnitude between host rock and fault damage zone and a decrease of 50% of the elastic properties between host rock and core zone. Data also show a higher dependence of the permeability on the effective pressure for the host rock compared with the damage zone and core zone. This heterogeneity of properties is related to the development of different microstructures such as microcracks, S-C structures and microbreccia across the fault zone achieved during the tectonic history of the fault. From these physical property values and the fault zone architecture, we then analyzed the effects of sudden mechanical loading approximating to static normal-stress transfer following an earthquake on a neighbouring fault, on the development of fluid overpressures. A series of 1-D hydromechanical numerical models was used to show that sudden normal stress increase is a viable mechanism for fluid overpressuring in the studied fault-zone. The models also showed that fluid overpressures can be temporarily maintained in the studied fault zone and that the maintenance of fluid overpressures is controlled by the structure and fluid-flow properties of the fault zone.

Impact evaluation of α-lipoic acid in gamma-irradiated erythrocytes

NASA Astrophysics Data System (ADS)

Desouky, Omar S.; Selim, Nabila S.; Elbakrawy, Eman M.; Rezk, Rezk A.

2011-03-01

This work is intended to study in vitro the ability of lipoic acid to protect erythrocytes against the oxidative damage resulting from exposure to gamma radiation through measurement of their rheological properties and to study the effects of detergent on their membrane solubility and permeability. Different doses of gamma radiation were applied: the most recommended and applied dose (25 Gy), and two higher doses, namely 50 and 100 Gy. The effect of addition of lipoic acid as well as its effect as a radioprotector was tested. The obtained results show changes in structural integrity of the erythrocyte cell membrane components as a result of oxidative damage due to gamma radiation that could be improved by pre-treatment with the antioxidant lipoic acid.

Metal chelator combined with permeability enhancer ameliorates oxidative stress-associated neurodegeneration in rat eyes with elevated intraocular pressure

PubMed Central

Liu, P.; Zhang, M.; Shoeb, M.; Hogan, D.; Tang, Luosheng; Syed, M. F.; Wang, C. Z.; Campbell, G.A.; Ansari, N.H.

2014-01-01

Since as many as half of glaucoma patients on intraocular pressure (IOP)-lowering therapy continue to experience optic nerve toxicity, it is imperative to find other effective therapies. Iron and calcium ions play key roles in oxidative stress, a hallmark of glaucoma. Therefore, we tested metal chelation by means of ethylenediaminetetraacetic acid (EDTA) combined with the permeability enhancer methyl sulfonyl methane (MSM) applied topically on the eye to determine if this non-invasive treatment is neuroprotective in rat optic nerve and retinal ganglion cells exposed to oxidative stress induced by elevated IOP. Hyaluronic acid (HA) was injected in the anterior chamber of the rat eye to elevate the IOP. EDTA-MSM was applied topically to the eye for 3 months. Eyeballs and optic nerves were processed for histological assessment of cytoarchitecture. Protein-lipid aldehyde adducts, and cyclooxygnease-2 (COX-2) were detected immunohistochemically. HA administration increased IOP and associated oxidative stress and inflammation. Elevated IOP was not affected by EDTA-MSM treatment. However oxidative damage and inflammation were ameliorated as reflected by decrease in formation of protein-lipid aldehyde adducts and COX-2 expression, respectively. Furthermore, EDTA-MSM treatment increased retinal ganglion cell survival and decreased demyelinization of optic nerve compared with untreated eyes. Chelation treatment with EDTA-MSM ameliorates sequelae of IOP-induced toxicity without affecting IOP. Since most current therapies aim at reducing IOP and damage occurs even in the absence of elevated IOP, EDTA-MSM has the potential to work in conjunction with pressure-reducing therapies to alleviate damage to the optic nerve and retinal ganglion cells. PMID:24509160

Characterizing Excavation Damaged Zone and Stability of Pressurized Lined Rock Caverns for Underground Compressed Air Energy Storage

NASA Astrophysics Data System (ADS)

Kim, Hyung-Mok; Rutqvist, Jonny; Jeong, Ju-Hwan; Choi, Byung-Hee; Ryu, Dong-Woo; Song, Won-Kyong

2013-09-01

In this paper, we investigate the influence of the excavation damaged zone (EDZ) on the geomechanical performance of compressed air energy storage (CAES) in lined rock caverns. We conducted a detailed characterization of the EDZ in rock caverns that have been excavated for a Korean pilot test program on CAES in (concrete) lined rock caverns at shallow depth. The EDZ was characterized by measurements of P- and S-wave velocities and permeability across the EDZ and into undisturbed host rock. Moreover, we constructed an in situ concrete lining model and conducted permeability measurements in boreholes penetrating the concrete, through the EDZ and into the undisturbed host rock. Using the site-specific conditions and the results of the EDZ characterization, we carried out a model simulation to investigate the influence of the EDZ on the CAES performance, in particular related to geomechanical responses and stability. We used a modeling approach including coupled thermodynamic multiphase flow and geomechanics, which was proven to be useful in previous generic CAES studies. Our modeling results showed that the potential for inducing tensile fractures and air leakage through the concrete lining could be substantially reduced if the EDZ around the cavern could be minimized. Moreover, the results showed that the most favorable design for reducing the potential for tensile failure in the lining would be a relatively compliant concrete lining with a tight inner seal, and a relatively stiff (uncompliant) host rock with a minimized EDZ. Because EDZ compliance depends on its compressibility (or modulus) and thickness, care should be taken during drill and blast operations to minimize the damage to the cavern walls.

Reservoir Structure and Wastewater-Induced Seismicity at the Val d'Agri Oilfield (Italy) Shown by Three-Dimensional Vp and Vp/Vs Local Earthquake Tomography

NASA Astrophysics Data System (ADS)

Improta, L.; Bagh, S.; De Gori, P.; Valoroso, L.; Pastori, M.; Piccinini, D.; Chiarabba, C.; Anselmi, M.; Buttinelli, M.

2017-11-01

Wastewater injection into a high-rate well in the Val d'Agri oilfield, the largest in onshore Europe, has induced swarm microseismicity since the initiation of disposal in 2006. To investigate the reservoir structure and to track seismicity, we performed a high-spatial resolution local earthquake tomography using 1,281 natural and induced earthquakes recorded by local networks. The properties of the carbonate reservoir (rock fracturing, pore fluid pressure) and inherited faults control the occurrence and spatiotemporal distribution of seismicity. A low-Vp, high-Vp/Vs region under the well represents a fluid saturated fault zone ruptured by induced seismicity. High-Vp, high-Vp/Vs bumps match reservoir culminations indicating saturated liquid-bearing zones, whereas a very low Vp, low Vp/Vs anomaly might represent a strongly fractured and depleted zone of the hydrocarbon reservoir characterized by significant fluid withdrawal. The comprehensive picture of the injection-linked seismicity obtained by integrating reservoir-scale tomography, high-precision earthquake locations, and geophysical and injection data suggests that the driving mechanism is the channeling of pore pressure perturbations through a high permeable fault damage zone within the reservoir. The damage zone surrounds a Pliocene reverse fault optimally oriented in the current extensional stress field. The ruptured damage zone measures 2 km along strike and 3 km along dip and is confined between low permeability ductile formations. Injection pressure is the primary parameter controlling seismicity rate. Our study underlines that local earthquake tomography also using wastewater-induced seismicity can give useful insights into the physical mechanism leading to these earthquakes.

The development and evaluation of advanced Kevlar sandwich structure for application to rotorcraft airframes

NASA Astrophysics Data System (ADS)

Minguet, Pierre; Llorente, Steven; Fay, Russell

1991-05-01

The results of an evaluation of DuPont Kevlar-based material systems in sandwich structure designed for rotorcraft primary airframe structure are presented in this report. The focus of this work has been to evaluate the durability and compression strength of thin-gage Kevlar sandwich panels and investigate means of improvement. It was found that sandwich panels made with Kevlar 149 fibers can be as strong as Kevlar 49 structures but have reduced compression stiffness properties at typical operating strain levels. Thermal cycling was found to affect permeability but not strength in thin facesheet sandwich structure. Any increased permeability can be prevented with the use of an interleaf or surfacing plies. The surfacing plies investigated also had a beneficial effect on sandwich strength due to their stabilizing effect on the facesheet in compression. Finally, a previously developed model was used to analyze the residual strength of a sandwich panel after impact damage.

Single-walled carbon nanotube, multi-walled carbon nanotube and Fe2O3 nanoparticles induced mitochondria mediated apoptosis in melanoma cells.

PubMed

Naserzadeh, Parvaneh; Ansari Esfeh, Fatemeh; Kaviani, Mahboubeh; Ashtari, Khadijeh; Kheirbakhsh, Raheleh; Salimi, Ahmad; Pourahmad, Jalal

2018-06-01

Nanomaterials (NM) exhibit novel anticancer properties. The toxicity of three nanoparticles that are currently being produced in high tonnage including single-walled carbon nanotube (SWCNT), multi-walled carbon nanotube (MWCNT) and Fe 2 O 3 nanoparticles, were compared with normal and melanoma cells. All tested nanoparticles induced selective toxicity and caspase 3 activation through mitochondria pathway in melanoma cells and mitochondria cause the generating of reactive oxygen species (ROS), mitochondrial membrane potential decline (MMP collapse), mitochondria swelling, and cytochrome c release. The pretreatment of butylated hydroxytoluene (BHT), a cell-permeable antioxidant and cyclosporine A (Cs. A), a mitochondrial permeability transition (MPT), pore sealing agent decreased cytotoxicity, caspase 3 activation, ROS generation, and mitochondrial damages induced by SWCNT, MWCNT, and IONPs. Our promising results provide a potential approach for the future therapeutic use of SWCNT, MWCNT, and IONPs in melanoma through mitochondrial targeting.

Effects of the air–steam mixture on the permeability of damaged concrete

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medjigbodo, Sonagnon; Darquennes, Aveline; Aubernon, Corentin

Massive concrete structures such as the containments of nuclear power plant must maintain their tightness at any circumstances to prevent the escape of radioactive fission products into the environment. In the event of an accident like a Loss of Coolant Accident (LOCA), the concrete wall is submitted to both hydric and mechanical loadings. A new experimental device reproducing these extreme conditions (water vapor transfer, 140 °C and 5 bars) is developed in the GeM Laboratory to determine the effect of the saturation degree, the mechanical loading and the flowing fluid type on the concrete transfer properties. The experimental tests showmore » that the previous parameters significantly affect the concrete permeability and the gas leakage rate. Their evolution as a function of the mechanical loading is characterized by two phases that are directly related to concrete microstructure and crack development.« less

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells.

PubMed

Lowes, Damon A; Wallace, Carol; Murphy, Michael P; Webster, Nigel R; Galley, Helen F

2009-04-01

Tendinitis and tendon rupture during treatment with fluoroquinolone antibiotics is thought to be mediated via oxidative stress. This study investigated whether ciprofloxacin and moxifloxacin cause oxidative stress and mitochondrial damage in cultured normal human Achilles' tendon cells and whether an antioxidant targeted to mitochondria (MitoQ) would protect against such damage better than a non-mitochondria targeted antioxidant. Human tendon cells from normal Achilles' tendons were exposed to 0-0.3 mM antibiotic for 24 h and 7 days in the presence of 1 microM MitoQ or an untargeted form, idebenone. Both moxifloxacin and ciprofloxacin resulted in up to a 3-fold increase in the rate of oxidation of dichlorodihydrofluorescein, a marker of general oxidative stress in tenocytes (p<0.0001) and loss of mitochondrial membrane permeability (p<0.001). In cells treated with MitoQ the oxidative stress was less and mitochondrial membrane potential was maintained. Mitochondrial damage to tenocytes during fluoroquinolone treatment may be involved in tendinitis and tendon rupture.

Earthquake-driven fluid flow rates inferred from borehole temperature measurements within the Japan Trench plate boundary fault zone

NASA Astrophysics Data System (ADS)

Fulton, P. M.; Brodsky, E. E.

2016-12-01

Using borehole sub-seafloor temperature measurements, we have recently identified signatures suggestive of earthquake-driven fluid pulses within the Japan Trench plate boundary fault zone during a major aftershock sequence. Here we use numerical models to show that these signatures are consistent with time-varying fluid flow rates out of permeable zones within the formation into the borehole annulus. In addition, we also identify an apparent time-varying sensitivity of whether suspected fluid pulses occur in response to earthquakes of a given magnitude and distance. The results suggest a damage and healing process and therefore provides a mechanism to allow for a disproportionate amount of heat and chemical transport in the short time frame after an earthquake. Our observations come from an observatory installed across the main plate boundary fault as part of IODP's Japan Trench Fast Drilling Project (JFAST) following the March 2011 Mw 9.0 Tohoku-oki earthquake. It operated from July 2012 - April 2013 during which a Mw 7.3 earthquake and numerous aftershocks occurred. High-resolution temperature time series data reveal spatially correlated transients in response to earthquakes with distinct patterns interpreted to reflect advection by transient pulses of fluid flow from permeable zones into the borehole annulus. Typical transients involve perturbations over 12 m with increases of 10 mK that build over 0.1 days at shallower depths and decreases at deeper depths. They are consistently centered around 792.5 m below seafloor (mbsf) where a secondary fault and permeable zone have been independently identified within the damage zone above the main plate boundary fault at 820 mbsf . Model simulations suggest transient flow rates of up to 10-3m/s from the formation that quickly decrease. Comparison of characteristics of earthquakes identified in nearby ocean bottom pressure measurements suggest there is not a clear relationship between fluid pulses and static strain. There does appear to be a time-varying sensitivity likely from dynamic stresses suggestive of a damage process followed by healing over 1 month time. The transient redistribution of fluid pressures and fluid flow within fault zones inferred here is a potential mechanism for earthquake triggering and episodic heat and chemical transport.

Cross-Shore Numerical Model CSHORE for Waves, Currents, Sediment Transport and Beach Profile Evolution

DTIC Science & Technology

2012-09-01

still water shoreline. This modification is necessary for a berm that is slanted downward toward the toe of a dune . The wet probability Pw on the...high dune provides storm protection and damage reduction, recreational and economical benefits, and biological habitats for plants and animals. Most...has been used to predict wave overwash of dunes . The hydrodynamic model has also been extended to the wet and dry zone on a permeable bottom for

Effect of various filler types on the properties of porous asphalt mixture

NASA Astrophysics Data System (ADS)

Shukry, Nurul Athma Mohd; Hassan, Norhidayah Abdul; Ezree Abdullah, Mohd; Rosli Hainin, Mohd; Yusoff, Nur Izzi Md; Putra Jaya, Ramadhansyah; Mohamed, Azman

2018-04-01

The open structure of porous asphalt exposes a large surface area to the effects of air and water, which accelerates the oxidation rate and affects the coating properties of the binder. These factors may influence the adhesive strength of the binder-aggregate and lead to cohesive failure within the binder film, contributing to aggregate stripping and moisture damage. The addition of fillers in asphalt mixtures has been identified to stiffen the asphalt binder and improve mixture strength. This study investigates the effect of various filler types (hydrated lime, cement, and diatomite) on the properties of porous asphalt. Compacted samples of porous asphalt were prepared using Superpave gyratory compactor at the target air void content of 21%. Each sample was incorporated with 2% of filler and polymer-modified binder of PG76. The morphology and chemical composition of fillers were investigated with a field emission scanning electron microscope (FESEM) and energy dispersive X-ray (EDX) analysis. The properties of porous asphalt were evaluated in terms of permeability, abrasion loss, resilient modulus, and indirect tensile strength. All mixtures were found to show high permeability rates. Mixtures with hydrated lime exhibited lower abrasion loss compared to mixtures with cement and diatomite. The use of diatomite increases the resistance of the mixtures to rutting and moisture damage compared to other fillers as shown by the enhanced resilient modulus and indirect tensile strength.

Elevated immunoglobulin levels in the cerebrospinal fluid from lupus-prone mice

PubMed Central

Sidor, Michelle M.; Sakic, Boris; Malinowski, Paul M.; Ballok, David A.; Oleschuk, Curtis J.; Macri, Joseph

2006-01-01

The systemic autoimmune disease lupus erythematosus (SLE) is frequently accompanied by neuropsychiatric manifestations and brain lesions of unknown etiology. The MRL-lpr mice show behavioral dysfunction concurrent with progression of a lupus-like disease, thus providing a valuable model in understanding the pathogenesis of autoimmunity-induced CNS damage. Profound neurodegeneration in the limbic system of MRL-lpr mice is associated with cytotoxicity of their cerebrospinal fluid (CSF) to mature and immature neurons. We have recently shown that IgG-rich CSF fraction largely accounts for this effect. The present study examines IgG levels in serum and CSF, as well as the permeability of the blood–brain barrier in mice that differ in immune status, age, and brain morphology. In comparison to young MRL-lpr mice and age-matched congenic controls, a significant elevation of IgG and albumin levels were detected in the CSF of aged autoimmune MRL-lpr mice. Two-dimensional gel electrophoresis and MALDI-TOF MS confirmed elevation in IgG heavy and Ig light chain isoforms in the CSF. Increased permeability of the blood–brain barrier correlated with neurodegeneration (as revealed by Fluoro Jade B staining) in periventricular areas. Although the source and specificity of neuropathogenic antibodies remain to be determined, these results support the hypothesis that a breached blood–brain barrier and IgG molecules are involved in the etiology of CNS damage during SLE-like disease. PMID:15972238

Coupled fluid and solid mechanics study for improved permeability estimation of fines' invaded porous materials

NASA Astrophysics Data System (ADS)

Mirabolghasemi, M.; Prodanovic, M.

2012-12-01

The problem of fine particle infiltration is seen in fields from subsurface transport, to drug delivery to industrial slurry flows. Sediment filtration and pathogen retention are well-known subsurface engineering problems that have been extensively studied through different macroscopic, microscopic and experimental modeling techniques Due to heterogeneity, standard constitutive relationships and models yield poor predictions for flow (e.g. permeability) and rock properties (e.g. elastic moduli) of the invaded (damaged) porous media. This severely reduces our ability to, for instance, predict retention, pressure build-up, newly formed flow pathways or porous medium mechanical behavior. We chose a coupled computational fluid dynamics (CFD) - discrete element modeling (DEM) approach to simulate the particulate flow through porous media represented by sphere packings. In order to minimize the uncertainty involved in estimating the flow properties of porous media on Darcy scale and address the dynamic nature of filtration process, this microscopic approach is adapted as a robust method that can incorporate particle interaction physics as well as the heterogeneity of the porous medium.. The coupled simulation was done in open-source packages which has both CFD (openFOAM) and DEM components (LIGGGHTS). We ran several sensitivity analyses over different parameters such as particle/grain size ratio, fluid viscosity, flow rate and sphere packing porosity in order to investigate their effects on the depth of invasion and damaged porous medium permeability. The response of the system to the variation of different parameters is reflected through different clogging mechanism; for instance, bridging is the dominant mechanism of pore-throat clogging when larger particles penetrate into the packing, whereas, in case of fine particles which are much smaller than porous medium grains (1/20 in diameter), this mechanism is not very effective due to the frequent formation and destruction of particle bridges. Finally, depending on the material and fluids that penetrate into the porous medium, the ionic forces might play a significant role in the filtration process. We thus also report on influence of particle attachment (and detachment) on the type of clogging mechanisms. Pore scale simulations allow for visualization and understanding of fundamental processes, and, further, the velocity fields are integrated into a distinctly non-monotonic permeability-porosity/(depth of penetration) relationship.

Frictional and hydraulic behaviour of carbonate fault gouge during fault reactivation - An experimental study

NASA Astrophysics Data System (ADS)

Delle Piane, Claudio; Giwelli, Ausama; Clennell, M. Ben; Esteban, Lionel; Nogueira Kiewiet, Melissa Cristina D.; Kiewiet, Leigh; Kager, Shane; Raimon, John

2016-10-01

We present a novel experimental approach devised to test the hydro-mechanical behaviour of different structural elements of carbonate fault rocks during experimental re-activation. Experimentally faulted core plugs were subject to triaxial tests under water saturated conditions simulating depletion processes in reservoirs. Different fault zone structural elements were created by shearing initially intact travertine blocks (nominal size: 240 × 110 × 150 mm) to a maximum displacement of 20 and 120 mm under different normal stresses. Meso-and microstructural features of these sample and the thickness to displacement ratio characteristics of their deformation zones allowed to classify them as experimentally created damage zones (displacement of 20 mm) and fault cores (displacement of 120 mm). Following direct shear testing, cylindrical plugs with diameter of 38 mm were drilled across the slip surface to be re-activated in a conventional triaxial configuration monitoring the permeability and frictional behaviour of the samples as a function of applied stress. All re-activation experiments on faulted plugs showed consistent frictional response consisting of an initial fast hardening followed by apparent yield up to a friction coefficient of approximately 0.6 attained at around 2 mm of displacement. Permeability in the re-activation experiments shows exponential decay with increasing mean effective stress. The rate of permeability decline with mean effective stress is higher in the fault core plugs than in the simulated damage zone ones. It can be concluded that the presence of gouge in un-cemented carbonate faults results in their sealing character and that leakage cannot be achieved by renewed movement on the fault plane alone, at least not within the range of slip measureable with our apparatus (i.e. approximately 7 mm of cumulative displacement). Additionally, it is shown that under sub seismic slip rates re-activated carbonate faults remain strong and no frictional weakening was observed during re-activation.

Zinc enhances intestinal epithelial barrier function through the PI3K/AKT/mTOR signaling pathway in Caco-2 cells.

PubMed

Shao, Yuxin; Wolf, Patricia G; Guo, Shuangshuang; Guo, Yuming; Gaskins, H Rex; Zhang, Bingkun

2017-05-01

Zinc plays an important role in maintaining intestinal barrier function as well as modulating cellular signaling recognition and protein kinase activities. The phosphatidylinositol 3-kinase (PI3K) cascade has been demonstrated to affect intercellular integrity and tight junction (TJ) proteins. The current study investigated the hypothesis that zinc regulates intestinal intercellular junction integrity through the PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. A transwell model of Caco-2 cell was incubated with 0, 50 and 100 μM of zinc at various time points. Transepithelial electrical resistance (TEER), paracellular permeability, TJ proteins, cell proliferation, differentiation and cell damage were measured. Compared with controls, 50 and 100 μM of zinc increased cell growth at 6, 12 and 24 h and the expression of proliferating cell nuclear antigen at 24 h. Zinc (100 μM) significantly elevated TEER at 6-24 h and reduced TJ permeability at 24 h, accompanied by the up-regulation of alkaline phosphatase (AP) activity and zonula occludens (ZO)-1 expression. In addition, zinc (100 μM) affected the PI3K/AKT/mTOR pathway by stimulating phosphorylation of AKT and the downstream target mTOR. Inhibition of PI3K signaling by LY294002 counteracted zinc promotion, as shown by a decrease in AP activity, TEER, the abundance of ZO-1 and phosphorylation of AKT and mTOR. Additionally, TJ permeability and the expression of caspase-3 and LC3II (markers of cell damage) were increased by addition of PI3K inhibitor. In conclusion, the activation of PI3K/AKT/mTOR signaling by zinc is involved in improving intestinal barrier function by enhancing cell differentiation and expression of TJ protein ZO-1. Copyright © 2017 Elsevier Inc. All rights reserved.

Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats.

PubMed

Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye; Johansson, Pär Ingemar

2017-03-01

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG ® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51 Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.

Structural and petrophysical characterization: from outcrop rock analogue to reservoir model of deep geothermal prospect in Eastern France

NASA Astrophysics Data System (ADS)

Bertrand, Lionel; Géraud, Yves; Diraison, Marc; Damy, Pierre-Clément

2017-04-01

The Scientific Interest Group (GIS) GEODENERGIES with the REFLET project aims to develop a geological and reservoir model for fault zones that are the main targets for deep geothermal prospects in the West European Rift system. In this project, several areas are studied with an integrated methodology combining field studies, boreholes and geophysical data acquisition and 3D modelling. In this study, we present the results of reservoir rock analogues characterization of one of these prospects in the Valence Graben (Eastern France). The approach used is a structural and petrophysical characterization of the rocks outcropping at the shoulders of the rift in order to model the buried targeted fault zone. The reservoir rocks are composed of fractured granites, gneiss and schists of the Hercynian basement of the graben. The matrix porosity, permeability, P-waves velocities and thermal conductivities have been characterized on hand samples coming from fault zones at the outcrop. Furthermore, fault organization has been mapped with the aim to identify the characteristic fault orientation, spacing and width. The fractures statistics like the orientation, density, and length have been identified in the damaged zones and unfaulted blocks regarding the regional fault pattern. All theses data have been included in a reservoir model with a double porosity model. The field study shows that the fault pattern in the outcrop area can be classified in different fault orders, with first order scale, larger faults distribution controls the first order structural and lithological organization. Between theses faults, the first order blocks are divided in second and third order faults, smaller structures, with characteristic spacing and width. Third order fault zones in granitic rocks show a significant porosity development in the fault cores until 25 % in the most locally altered material, as the damaged zones develop mostly fractures permeabilities. In the gneiss and schists units, the matrix porosity and permeability development is mainly controlled by microcrack density enhancement in the fault zone unlike the granite rocks were it is mostly mineral alteration. Due to the grain size much important in the gneiss, the opening of the cracks is higher than in the schist samples. Thus, the matrix permeability can be two orders higher in the gneiss than in the schists (until 10 mD for gneiss and 0,1 mD for schists for the same porosity around 5%). Combining the regional data with the fault pattern, the fracture and matrix porosity and permeability, we are able to construct a double-porosity model suitable for the prospected graben. This model, combined with seismic data acquisition is a predictable tool for flow modelling in the buried reservoir and helps the prediction of borehole targets and design in the graben.

Effect of retinol on the hyperthermal response of normal tissue in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, M.A.; Marigold, J.C.L.; Hume, S.P.

The effect of prior administration of retinol, a membrane labilizer, on the in vivo hyperthermal response of lysosomes was investigated in the mouse spleen using a quantitative histochemical assay for the lysosomal enzyme acid phosphatase. A dose of retinol which had no effect when given alone enhanced the thermal response of the lysosome, causing an increase in lysosomal membrane permeability. In contrast, the same dose of retinol had no effect on the gross hyperthermal response of mouse intestine; a tissue which is relatively susceptible to hyperthermia. Thermal damage to intestine was assayed directly by crypt loss 1 day after treatmentmore » or assessed as thermal enhancement of x-ray damage by counting crypt microcolonies 4 days after a combined heat and x-ray treatment. Thus, although the hyperthermal response of the lysosome could be enhanced by the administration of retinol, thermal damage at a gross tissue level appeared to be unaffected, suggesting that lysosomal membrane injury is unlikely to be a primary event in hyperthermal cell killing.« less

Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening.

PubMed

Sun, Wen-xiao; Zheng, Hai-ya; Lan, Jun

2015-11-01

Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.

Role of ROS and RNS Sources in Physiological and Pathological Conditions

PubMed Central

Victor, Victor Manuel

2016-01-01

There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis. PMID:27478531

Heat-resistant agent used for control sand of steam huff and puff heavy oil well

NASA Astrophysics Data System (ADS)

Zhang, F. S.; Liu, G. L.; Lu, Y. J.; Xiong, X. C.; Ma, J. H.; Su, H. M.

2018-01-01

Heat-resistant agent containing hydroxymethyl group was synthesized from coal tar, which has similar structure with phenolic resin and could improve the heat resistance of phenolic resin sand control agent. The results showed that the heat resistance of the sand control agent was improved by adding 10% to 30% heat-resistant agent, after 280°C high temperature treatment for 7d, the compressive strength of consolidated core was increased to more than 5MPa. The compressive strength of consolidation core was not decreased after immersion in formation water, crude oil, acid or alkaline medium, which showed good resistance to medium immersion. The sand control agent had small core damage and the core permeability damage ratio of sand control agent consolidation was only 18.7%.

Receptor for advanced glycation end product expression in experimental diabetic retinopathy.

PubMed

Wang, Yumei; Vom Hagen, Franziska; Pfister, Frederick; Bierhaus, Angelika; Feng, Yuxi; Gans, Reinhold; Hammes, Hans-Peter

2008-04-01

The advanced glycation end product (AGE)-receptor for AGE (RAGE) pathway is involved in the pathogenesis of diabetic microvascular damage. The special distribution of RAGE and its engagement has an impact on the development of diabetic retinopathy. In the present study, we used immunofluorescence and confocal laser microscopy to study RAGE expression with special emphasis on Müller glia in Sprague Dawley rats. RAGE expression was low in nondiabetic retinae and was found in ganglion cells and Müller cell end feet. In diabetic retinae, upregulated RAGE was predominantly expressed in retinal glia. Since Müller cells are important in the regulation of important features of early retinal vascular damage, such as vascular permeability, homeostasis, and response to stress, RAGE appears to be a central modulator in diabetic retinopathy.

Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.

PubMed

Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie

2011-05-16

Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium.

PubMed

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-08-10

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage.

Paclitaxel-induced lung injury and its amelioration by parecoxib sodium

PubMed Central

Liu, Wen-jie; Zhong, Zhong-jian; Cao, Long-hui; Li, Hui-ting; Zhang, Tian-hua; Lin, Wen-qian

2015-01-01

To investigate the mechanism of paclitaxel-induced lung injury and its amelioration by parecoxib sodium. In this study, rats were randomly divided into: the control group (Con); the paclitaxel chemotherapy group (Pac); the paclitaxel+ parecoxib sodium intervention group (Pac + Pare); and the parecoxib sodium group (Pare). We observed changes in alveolar ventilation function, alveolar-capillary membrane permeability, lung tissue pathology and measured the levels of inflammatory cytokines and cyclooxygenase-2 (Cox-2) in lung tissue, the expression of tight junction proteins (Zo-1 and Claudin-4). Compared with the Con group, the lung tissue of the Pac group showed significantly increased expression of Cox-2 protein (p < 0.01), significant lung tissue inflammatory changes, significantly increased expression of inflammatory cytokines, decreased expression of Zo-1 and Claudin-4 proteins (p < 0.01), increased alveolar-capillary membrane permeability (p < 0.01), and reduced ventilation function (p < 0.01). Notably, in Pac + Pare group, intraperitoneal injection of parecoxib sodium led to decreased Cox-2 and ICAM-1 levels and reduced inflammatory responses, the recovered expression of Zo-1 and Claudin-4, reduced level of indicators reflecting the high permeability state, and close-to-normal levels of ventilation function. Intervention by the Cox-2-specific inhibitor parecoxib sodium can block this damage. PMID:26256764

Intestinal permeability in a patient with liver cirrhosis

PubMed Central

Aguirre Valadez, Jonathan Manuel; Rivera-Espinosa, Liliana; Méndez-Guerrero, Osvely; Chávez-Pacheco, Juan Luis; García Juárez, Ignacio; Torre, Aldo

2016-01-01

Liver cirrhosis is a worldwide public health problem, and patients with this disease are at high risk of developing complications, bacterial translocation from the intestinal lumen to the mesenteric nodes, and systemic circulation, resulting in the development of severe complications related to high mortality rate. The intestinal barrier is a structure with a physical and biochemical activity to maintain balance between the external environment, including bacteria and their products, and the internal environment. Patients with liver cirrhosis develop a series of alterations in different components of the intestinal barrier directly associated with the severity of liver disease that finally increased intestinal permeability. A “leaky gut” is an effect produced by damaged intestinal barrier; alterations in the function of tight junction proteins are related to bacterial translocation and their products. Instead, increasing serum proinflammatory cytokines and hemodynamics modification, which results in the appearance of complications of liver cirrhosis such as hepatic encephalopathy, variceal hemorrhage, bacterial spontaneous peritonitis, and hepatorenal syndrome. The intestinal microbiota plays a fundamental role in maintaining the proper function of the intestinal barrier; bacterial overgrowth and dysbiosis are two phenomena often present in people with liver cirrhosis favoring bacterial translocation. Increased intestinal permeability has an important role in the genesis of these complications, and treating it could be the base for prevention and partial treatment of these complications. PMID:27920543

Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.

PubMed

Dunér, Fredrik; Lindström, Karin; Hultenby, Kjell; Hulkko, Jenny; Patrakka, Jaakko; Tryggvason, Karl; Haraldsson, Börje; Wernerson, Annika; Pettersson, Erna

2010-01-01

It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas α-actinin was unchanged. Copyright © 2010 S. Karger AG, Basel.

Studies of the permeation properties of glomerular basement membrane: cross-linking renders glomerular basement membrane permeable to protein.

PubMed

Walton, H A; Byrne, J; Robinson, G B

1992-03-20

Cross-linking glomerular basement membrane (GBM) has been shown to render it more permeable to protein. Isolated pig GBM was cross-linked with dimethylmalonimidate which reacts selectively with lysine epsilon-NH2 groups or with glutaraldehyde, a less selective cross-linking agent. Studies of the ultrafiltration properties of these materials in vitro using cytochrome c, myoglobin, bovine serum albumin and immunoglobulin showed that cross-linking had markedly increased solvent and protein fluxes as compared with native membranes particularly at higher pressures. Filtration studies with serum demonstrated that the cross-linked membranes were more permeable to serum proteins. Thickness measurements under pressure indicated that cross-linked membrane was less compressed than native membrane as pressure was increased. Pore theory did not provide a suitable model for analysis of the results, but analysis of the results using the fibre-matrix hypothesis indicated that cross-linking had the effect of bundling together the fibres (type IV collagen) in the GBM matrix. The effect of cross-linking on filtration could be explained by a combination of contraction of the membrane, fibre bundling and increased rigidity compared with native membrane. Cross-linking of GBM might lead to long-term damage of the glomerular capillary wall in nephritis, so promoting proteinuria.

Mast Cell Activation Protects Cornea by Promoting Neutrophil Infiltration via Stimulating ICAM-1 and Vascular Dilation in Fungal Keratitis.

PubMed

Xie, Yanting; Zhang, Hongmin; Liu, Susu; Chen, Guoming; He, Siyu; Li, Zhijie; Wang, Liya

2018-05-30

The role of mast cells (MCs) in fungal infection is largely unknown. This study was to explore a protective role and mechanism of MCs in fungal keratitis. Experimental fungal keratitis (FK) mouse model was developed. Mice untreated (UT) or receiving corneal wound without fungal infection (Mock) were used as controls. Large number of connective tissue MCs was found in normal mice. MC activation with degranulation was largely observed, and the percentage of degranulated/total cells was high in FK. Dilated limbal vasculature with increased permeability, as well as largely infiltrated neutrophils with stimulated ICAM-1 protein levels were observed in corneas of FK mice, when compared with Mock and UT mice. Interestingly, pretreatment with cromolyn sodium (Block) significantly blocked MC degranulation, dramatically suppressed vascular dilation and permeability, and markedly reduced neutrophil infiltration with lower ICAM-1 levels in FK mice at 6-24 hours. Furthermore, the Block mice manifested prolonged disease course, increased pathological damage, and vigorous fungus growth, with much higher corneal perforation rate than FK mice at 72 h. These findings reveal a novel phenomenon that MCs play a vital role in protecting cornea against fungal infection through degranulation that promotes neutrophil infiltration via stimulating ICAM-1 production and limbal vascular dilation and permeability.

Recombinant Human Sonic Hedgehog Protein Regulates the Expression of ZO-1 and Occludin by Activating Angiopoietin-1 in Stroke Damage

PubMed Central

Chen, Sheng-cai; Huang, Ming; Wang, Yong; Gao, Yuan; Huang, Yan; Wang, Meng-die; Mao, Ling; Hu, Bo

2013-01-01

This study examines the regulating effect of Sonic Hedgehog (Shh) on the permeability of the blood-brain barrier (BBB) in cerebral ischemia. By employing permanent middle cerebral artery occlusion (pMCAO) model, we find that Shh significantly decreases brain edema and preserves BBB permeability. Moreover, Shh increases zonula occludens-1 (ZO-1), occludin and angiopiotetin-1 (Ang-1) expression in the ischemic penumbra. Blockage of Shh with cyclopamine abolishes the effects of Shh on brain edema, BBB permeability and ZO-1, occludin, Ang-1 expression. Primary brain microvessel endothelial cells (BMECs) and astrocytes were pre-treated with Shh, cyclopamine, Ang-1-neutralizing antibody, and subjected to oxygen-glucose deprivation (OGD). Results show that the Ang-1 protein level in the culture medium of Shh-treated astrocytes is significantly higher. Shh also increased ZO-1, occludin and Ang-1 expression in BMECs, while cyclopamine and Ang-1-neutralizing antibody inhibited the effects of Shh on the ZO-1 and occludin expression, respectively. This study suggests that, under ischemic insults, Shh triggers Ang-1 production predominantly in astrocytes, and the secreted Ang-1 acts on BMECs, thereby upregulating ZO-1 and occludin to repair the tight junction and ameliorate the brain edema and BBB leakage. PMID:23894369

Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection

PubMed Central

Gunnarson, Eli; Song, Yutong; Kowalewski, Jacob M.; Brismar, Hjalmar; Brines, Michael; Cerami, Anthony; Andersson, Ulf; Zelenina, Marina; Aperia, Anita

2009-01-01

Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water uptake. Here we report that erythropoietin (EPO), which in recent years has emerged as a potent neuro-protective agent, antagonizes the effect of a group I mGluR agonist on astrocyte water permeability. Activation of group I mGluRs triggers fast and highly regular intracellular calcium oscillations and we show that EPO interferes with this signaling event by altering the frequency of the oscillations. These effects of EPO are immediate, in contrast to the neuroprotective effects of EPO that are known to depend upon gene activation. Our findings indicate that EPO may directly reduce the risk of astrocyte swelling in stroke and other brain insults. In support of this conclusion we found that EPO reduced the neurological symptoms in a mouse model of primary brain edema known to depend upon AQP4 water transport. PMID:19164545

Fault-related structural permeability: Qualitative insights of the damage-zone from micro-CT analysis.

NASA Astrophysics Data System (ADS)

Gomila, Rodrigo; Arancibia, Gloria; Nehler, Mathias; Bracke, Rolf; Stöckhert, Ferdinand

2016-04-01

Fault zones and their related structural permeability play a leading role in the migration of fluids through the continental crust. A first approximation to understanding the structural permeability conditions, and the estimation of its hydraulic properties (i.e. palaeopermeability and fracture porosity conditions) of the fault-related fracture mesh is the 2D analysis of its veinlets, usually made in thin-section. Those estimations are based in the geometrical parameters of the veinlets, such as average fracture density, length and aperture, which can be statistically modelled assuming penny-shaped fractures of constant radius and aperture within an anisotropic fracture system. Thus, this model is related to fracture connectivity, its length and to the cube of the fracture apertures. In this way, the estimated values presents their own inaccuracies owing to the method used. Therefore, the study of the real spatial distribution of the veinlets of the fault-related fracture mesh (3D), feasible with the use of micro-CT analyses, is a first order factor to unravel both, the real structural permeability conditions of a fault-zone, together with the validation of previous estimations made in 2D analyses in thin-sections. This early contribution shows the preliminary results of a fault-related fracture mesh and its 3D spatial distribution in the damage zone of the Jorgillo Fault (JF), an ancient subvertical left-lateral strike-slip fault exposed in the Atacama Fault System in northern Chile. The JF is a ca. 20 km long NNW-striking strike-slip fault with sinistral displacement of ca. 4 km. The methodology consisted of the drilling of vertically oriented plugs of 5 mm in diameter located at different distances from the JF core - damage zone boundary. Each specimen was, then, scanned with an x-ray micro-CT scanner (ProCon X-Ray CTalpha) in order to assess the fracture mesh. X-rays were generated in a transmission target x-ray tube with acceleration voltages ranging from 90-120 kV and target currents from 40-60 μA. The focal spot size on the diamond/tungsten target was about 5 μm. The x-ray beam was filtered using a 1 mm Aluminum plate before passing the sample. 1200 x-ray images were taken during a full rotation of the sample using an amorphous silicon flat panel detector with 1516x1900 pixels. This resulted in a voxel resolution of about 8 μm in the 3D data reconstructed from the images. Future work will be aimed in the images segmentation of the fault-related fracture mesh followed by the estimation of its hydraulic properties at the time of fracture sealing. Acknowledgements: This work is a contribution to the CONICYT- BMBF International Scientific Collaborative Research Program Project PCCI130025/FKZ01DN14033 and the FONDAP-CONICYT Project 15090013.

Hydromechanical heterogeneities of a mature fault zone: impacts on fluid flow.

PubMed

Jeanne, Pierre; Guglielmi, Yves; Cappa, Frédéric

2013-01-01

In this paper, fluid flow is examined for a mature strike-slip fault zone with anisotropic permeability and internal heterogeneity. The hydraulic properties of the fault zone were first characterized in situ by microgeophysical (VP and σc ) and rock-quality measurements (Q-value) performed along a 50-m long profile perpendicular to the fault zone. Then, the local hydrogeological context of the fault was modified to conduct a water-injection test. The resulting fluid pressures and flow rates through the different fault-zone compartments were then analyzed with a two-phase fluid-flow numerical simulation. Fault hydraulic properties estimated from the injection test signals were compared to the properties estimated from the multiscale geological approach. We found that (1) the microgeophysical measurements that we made yield valuable information on the porosity and the specific storage coefficient within the fault zone and (2) the Q-value method highlights significant contrasts in permeability. Fault hydrodynamic behavior can be modeled by a permeability tensor rotation across the fault zone and by a storativity increase. The permeability tensor rotation is linked to the modification of the preexisting fracture properties and to the development of new fractures during the faulting process, whereas the storativity increase results from the development of micro- and macrofractures that lower the fault-zone stiffness and allows an increased extension of the pore space within the fault damage zone. Finally, heterogeneities internal to the fault zones create complex patterns of fluid flow that reflect the connections of paths with contrasting properties. © 2013, The Author(s). Ground Water © 2013, National Ground Water Association.

The effects of long duration chronic exposure to hexavalent chromium on single live cells interrogated by scanning electrochemical microscopy.

PubMed

Filice, Fraser P; Li, Michelle S M; Wong, Jonathan M; Ding, Zhifeng

2018-05-01

Chromium is a useful heavy metal which has been employed in numerous industry and house applications. However, there are several known health risks associated with its uses. Cr (VI) is a toxic heavy metal format which serves no essential biological role in humans. It has been associated with oxidative stress, cytotoxicity, and carcinogenicity. Contamination of groundwater or soil due to improper handling lead to long term environmental damage. This study explores the effects of long duration chronic exposure to Cr (VI) on live human cells. Herein, scanning electrochemical microscopy (SECM) depth scan imaging was employed to monitor the membrane permeability of single live human bladder cancer (T24) cells following incubation with various Cr (VI) concentration stimuli. SECM was used to provide insights into the long duration effects on membrane homeostasis of individual cells exposed to constant levels of Cr (VI). Further investigation of total population viability was performed by MTT assay. Dependent on the exposure time, transition between three distinct trends was observed. At short incubation times (≤1-3 h) with low concentrations of Cr (VI) (0-10 μM), membrane permeability was largely unaffected. As time increased a decrease in membrane permeability coefficient was observed, reaching a minimum at 3-6 h. Following this a dramatic increase in membrane permeability was observed as cell viability decreased. Higher concentrations were also found to accelerate the timeframe at which these trends occurred. These findings further demonstrate the strength of SECM as a bioanalytical technique for monitoring cellular homeostasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective effects of skin permeable epidermal and fibroblast growth factor against ultraviolet-induced skin damage and human skin wrinkles.

PubMed

An, Jae Jin; Eum, Won Sik; Kwon, Hyuck Se; Koh, Jae Sook; Lee, Soo Yun; Baek, Ji Hwoon; Cho, Yong-Jun; Kim, Dae Won; Han, Kyu Huyng; Park, Jinseu; Jang, Sang Ho; Choi, Soo Young

2013-12-01

Epidermal and fibroblast growth factor (EGF and FGF1) proteins play an important role in the regeneration and proliferation of skin cells. EGF and FGF1 have considerable potential as possible therapeutic or cosmetic agents for the treatment of skin damage including wrinkles. Using protein transduction domains (PTD), we investigated whether PTD-EGF and FGF1 transduced into skin cells and tissue. Transduced proteins showed protective effects in a UV-induced skin damage model as well as against skin wrinkles. Transduced PTD-EGF and FGF1 proteins were detected by immunofluorescence and immunohistochemistry. The effects of PTD-EGF and FGF1 were examined by WST assay, Western blotting, immunohistochemistry, and skin wrinkle parameters. The PTD-EGF and FGF1 increased cell proliferation and collagen type 1 alpha 1 protein accumulation in skin tissue. Also, PTD-EGF and FGF1 inhibited UV-induced skin damage. Furthermore, topical application of PTD-EGF and FGF1 contained ampoules which were considered to improve the wrinkle parameters of human skin. These results show that PTD-EGF and FGF1 can be a potential therapeutic or cosmetic agent for skin damaged and injury including wrinkles and aging. © 2013 Wiley Periodicals, Inc.

Vascular tight junction disruption and angiogenesis in spontaneously hypertensive rat with neuroinflammatory white matter injury.

PubMed

Yang, Yi; Kimura-Ohba, Shihoko; Thompson, Jeffrey F; Salayandia, Victor M; Cossé, Melissa; Raz, Limor; Jalal, Fakhreya Y; Rosenberg, Gary A

2018-06-01

Vascular cognitive impairment is a major cause of dementia caused by chronic hypoxia, producing progressive damage to white matter (WM) secondary to blood-brain barrier (BBB) opening and vascular dysfunction. Tight junction proteins (TJPs), which maintain BBB integrity, are lost in acute ischemia. Although angiogenesis is critical for neurovascular remodeling, less is known about its role in chronic hypoxia. To study the impact of TJP degradation and angiogenesis during pathological progression of WM damage, we used the spontaneously hypertensive/stroke prone rats with unilateral carotid artery occlusion and Japanese permissive diet to model WM damage. MRI and IgG immunostaining showed regions with BBB damage, which corresponded with decreased endothelial TJPs, claudin-5, occludin, and ZO-1. Affected WM had increased expression of angiogenic factors, Ki67, NG2, VEGF-A, and MMP-3 in vascular endothelial cells and pericytes. To facilitate the study of angiogenesis, we treated rats with minocycline to block BBB disruption, reduce WM lesion size, and extend survival. Minocycline-treated rats showed increased VEGF-A protein, TJP formation, and oligodendrocyte proliferation. We propose that chronic hypoxia disrupts TJPs, increasing vascular permeability, and initiating angiogenesis in WM. Minocycline facilitated WM repair by reducing BBB damage and enhancing expression of TJPs and angiogenesis, ultimately preserving oligodendrocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Damage-Based Time-Dependent Modeling of Paraglacial to Postglacial Progressive Failure of Large Rock Slopes

NASA Astrophysics Data System (ADS)

Riva, Federico; Agliardi, Federico; Amitrano, David; Crosta, Giovanni B.

2018-01-01

Large alpine rock slopes undergo long-term evolution in paraglacial to postglacial environments. Rock mass weakening and increased permeability associated with the progressive failure of deglaciated slopes promote the development of potentially catastrophic rockslides. We captured the entire life cycle of alpine slopes in one damage-based, time-dependent 2-D model of brittle creep, including deglaciation, damage-dependent fluid occurrence, and rock mass property upscaling. We applied the model to the Spriana rock slope (Central Alps), affected by long-term instability after Last Glacial Maximum and representing an active threat. We simulated the evolution of the slope from glaciated conditions to present day and calibrated the model using site investigation data and available temporal constraints. The model tracks the entire progressive failure path of the slope from deglaciation to rockslide development, without a priori assumptions on shear zone geometry and hydraulic conditions. Complete rockslide differentiation occurs through the transition from dilatant damage to a compacting basal shear zone, accounting for observed hydraulic barrier effects and perched aquifer formation. Our model investigates the mechanical role of deglaciation and damage-controlled fluid distribution in the development of alpine rockslides. The absolute simulated timing of rock slope instability development supports a very long "paraglacial" period of subcritical rock mass damage. After initial damage localization during the Lateglacial, rockslide nucleation initiates soon after the onset of Holocene, whereas full mechanical and hydraulic rockslide differentiation occurs during Mid-Holocene, supporting a key role of long-term damage in the reported occurrence of widespread rockslide clusters of these ages.

Effects of Methylenedianiline on Tight Junction Permeability of Biliary Epithelial Cells in vivo and in vitro

PubMed Central

Santa Cruz, Vicente; Liu, Hanlin; Kaphalia, Lata; Kanz, Mary F.

2007-01-01

Methylenedianiline (DAPM) is considered a cholangiodestructive toxicant in vivo. Increases in biliary inorganic phosphate (Pi) and glucose occur prior to biliary epithelial cell (BEC) injury, which could be due to increased paracellular permeability and/or impairment of Pi and glucose uptake by BEC. To evaluate these possibilities, we induced mild injury [loss of BEC from major bile ducts (6 h), ultrastructural alterations in BEC mitochondria and Golgi cisternae (3 h), and striking increases in biliary Pi and glucose (3–6 h)] with 25 mg DAPM/kg and then assessed temporal alterations in tight junction (TJ) permeability by measuring bile to plasma (B:P) ratios of [3H]-inulin. Parameters maintained by hepatocytes in bile were unchanged (bile flow, bile acids, bilirubin) or only transiently perturbed (protein, glutathione). Minimal elevations in B:P ratios of inulin occurred temporally later (4 h) in DAPM-treated rats than increases in biliary Pi and glucose. To confirm a direct effect of DAPM on BEC TJs, we measured transepithelial resistance (TER) and bi-ionic potentials of BEC monolayers prior to and after exposure to pooled (4 to 6) bile samples collected from untreated rats (Basal Bile) or rats treated with 50 mg DAPM/ kg (DAPM-Bile). BEC TJs were found to be cation selective. Exposure to DAPM-Bile for 1 h decreased TERs by ~35% and decreased charge selectivity of BEC TJs while exposure to Basal Bile had no effects. These observations indicate that DAPM-Bile impairs paracellular permeability of BEC in vitro. Further, our in vivo model suggests that increases in paracellular permeability induced by DAPM are localized to BEC because bile flow and constituents excreted by hepatocytes were unchanged; BEC damage was temporally correlated with increases in biliary Pi and glucose; and elevations in B:P ratios of inulin were delayed and minimal. PMID:17178199

Ischemia-reperfusion impairs blood-brain barrier function and alters tight junction protein expression in the ovine fetus.

PubMed

Chen, X; Threlkeld, S W; Cummings, E E; Juan, I; Makeyev, O; Besio, W G; Gaitanis, J; Banks, W A; Sadowska, G B; Stonestreet, B S

2012-12-13

The blood-brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-brain barrier. Hypoxic-ischemic damage to the blood-brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood-brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood-brain barrier function in the fetus. Blood-brain barrier function was quantified with the blood-to-brain transfer constant (K(i)) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in K(i) (P<0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between K(i) and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-brain barrier function after ischemia. We conclude that impaired blood-brain barrier function is an important component of hypoxic-ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (K(i)) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood-brain barrier function improves early after injury because the blood-brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood-brain barrier permeability after ischemia. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Effectiveness of cuticular transpiration barriers in a desert plant at controlling water loss at high temperatures

PubMed Central

Schuster, Ann-Christin; Burghardt, Markus; Alfarhan, Ahmed; Bueno, Amauri; Hedrich, Rainer; Leide, Jana; Thomas, Jacob; Riederer, Markus

2016-01-01

Maintaining the integrity of the cuticular transpiration barrier even at elevated temperatures is of vital importance especially for hot-desert plants. Currently, the temperature dependence of the leaf cuticular water permeability and its relationship with the chemistry of the cuticles are not known for a single desert plant. This study investigates whether (i) the cuticular permeability of a desert plant is lower than that of species from non-desert habitats, (ii) the temperature-dependent increase of permeability is less pronounced than in those species and (iii) whether the susceptibility of the cuticular permeability barrier to high temperatures is related to the amounts or properties of the cutin or the cuticular waxes. We test these questions with Rhazya stricta using the minimum leaf water vapour conductance (gmin) as a proxy for cuticular water permeability. gmin of R. stricta (5.41 × 10−5 m s−1 at 25 °C) is in the upper range of all existing data for woody species from various non-desert habitats. At the same time, in R. stricta, the effect of temperature (15–50 °C) on gmin (2.4-fold) is lower than in all other species (up to 12-fold). Rhazya stricta is also special since the temperature dependence of gmin does not become steeper above a certain transition temperature. For identifying the chemical and physical foundation of this phenomenon, the amounts and the compositions of cuticular waxes and cutin were determined. The leaf cuticular wax (251.4 μg cm−2) is mainly composed of pentacyclic triterpenoids (85.2% of total wax) while long-chain aliphatics contribute only 3.4%. In comparison with many other species, the triterpenoid-to-cutin ratio of R. stricta (0.63) is high. We propose that the triterpenoids deposited within the cutin matrix restrict the thermal expansion of the polymer and, thus, prevent thermal damage to the highly ordered aliphatic wax barrier even at high temperatures. PMID:27154622

Exposure to 900 MHz electromagnetic fields activates the mkp-1/ERK pathway and causes blood-brain barrier damage and cognitive impairment in rats.

PubMed

Tang, Jun; Zhang, Yuan; Yang, Liming; Chen, Qianwei; Tan, Liang; Zuo, Shilun; Feng, Hua; Chen, Zhi; Zhu, Gang

2015-03-19

With the rapid increase in the number of mobile phone users, the potential adverse effects of the electromagnetic field radiation emitted by a mobile phone has become a serious concern. This study demonstrated, for the first time, the blood-brain barrier and cognitive changes in rats exposed to 900 MHz electromagnetic field (EMF) and aims to elucidate the potential molecular pathway underlying these changes. A total of 108 male Sprague-Dawley rats were exposed to a 900 MHz, 1 mW/cm(2) EMF or sham (unexposed) for 14 or 28 days (3h per day). The specific energy absorption rate (SAR) varied between 0.016 (whole body) and 2 W/kg (locally in the head). In addition, the Morris water maze test was used to examine spatial memory performance determination. Morphological changes were investigated by examining ultrastructural changes in the hippocampus and cortex, and the Evans Blue assay was used to assess blood brain barrier (BBB) damage. Immunostaining was performed to identify heme oxygenase-1 (HO-1)-positive neurons and albumin extravasation detection. Western blot was used to determine HO-1 expression, phosphorylated ERK expression and the upstream mediator, mkp-1 expression. We found that the frequency of crossing platforms and the percentage of time spent in the target quadrant were lower in rats exposed to EMF for 28 days than in rats exposed to EMF for 14 days and unexposed rats. Moreover, 28 days of EMF exposure induced cellular edema and neuronal cell organelle degeneration in the rat. In addition, damaged BBB permeability, which resulted in albumin and HO-1 extravasation were observed in the hippocampus and cortex. Thus, for the first time, we found that EMF exposure for 28 days induced the expression of mkp-1, resulting in ERK dephosphorylation. Taken together, these results demonstrated that exposure to 900 MHz EMF radiation for 28 days can significantly impair spatial memory and damage BBB permeability in rat by activating the mkp-1/ERK pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

Melatonin pretreatment enhances the therapeutic effects of exogenous mitochondria against hepatic ischemia-reperfusion injury in rats through suppression of mitochondrial permeability transition.

PubMed

Chen, Hong-Hwa; Chen, Yen-Ta; Yang, Chih-Chao; Chen, Kuan-Hung; Sung, Pei-Hsun; Chiang, Hsin-Ju; Chen, Chih-Hung; Chua, Sarah; Chung, Sheng-Ying; Chen, Yi-Ling; Huang, Tien-Hung; Kao, Gour-Shenq; Chen, Sheng-Yi; Lee, Mel S; Yip, Hon-Kan

2016-08-01

We tested the hypothesis that melatonin (Mel) enhances exogenous mitochondria (Mito) treatment against rodent hepatic ischemia-reperfusion (IR) injury. In vitro study utilized three groups of hepatocytes (i.e. nontreatment, menadione, and menadione-melatonin treatment, 4.0 × 10(5) each), while in vivo study used adult male Sprague Dawley rats (n = 40) equally divided into sham-control (SC), IR (60-min left-lobe ischemia + 72-hr reperfusion), IR-Mel (melatonin at 30 min/6/8 hr after reperfusion), IR-Mito (mitochondria 15,000 μg/rat 30 min after reperfusion), and IR-Mel-Mito. Following menadione treatment in vitro, oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (cleaved caspase-3/PARP), DNA damage (γ-H2AX/CD90/XRCC1), mitochondria damage (cytosolic cytochrome c) biomarkers, and mitochondrial permeability transition were found to be lower, whereas mitochondrial cytochrome c were found to be higher in hepatocytes with melatonin treatment compared to those without (all P < 0.001). In vivo study demonstrated highest liver injury score and serum AST in IR group, but lowest in SC group and higher in IR-Mito group than that in groups IR-Mel and IR-Mel-Mito, and higher in IR-Mel group than that in IR-Mel-Mito group after 72-hr reperfusion (all P < 0.003). Protein expressions of inflammatory (TNF-α/NF-κB/IL-1β/MMP-9), oxidative stress (NOX-1/NOX-2/oxidized protein), apoptotic (caspase-3/PARP/Bax), and mitochondria damage (cytosolic cytochrome c) biomarkers displayed an identical pattern, whereas mitochondria integrity marker (mitochondrial cytochrome c) showed an opposite pattern compared to that of liver injury score (all P < 0.001) among five groups. Microscopically, expressions of apoptotic nuclei, inflammatory (MPO(+) /CD68(+) /CD14(+) cells), and DNA damage (γ-H2AX(+) cells) biomarkers exhibited an identical pattern compared to that of liver injury score (all P < 0.001) among five groups. Melatonin-supported mitochondria treatment offered an additional benefit of alleviating hepatic IR injury. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Damage and Geochemical Signature of a Crustal Scale Strike-Slip Fault Zone

NASA Astrophysics Data System (ADS)

Gomila, R.; Mitchell, T. M.; Arancibia, G.; Jensen Siles, E.; Rempe, M.; Cembrano, J. M.; Faulkner, D. R.

2013-12-01

Fluid-flow migration in the upper crust is strongly controlled by fracture network permeability and connectivity within fault zones, which can lead to fluid-rock chemical interaction represented as mineral precipitation in mesh veins and/or mineralogical changes (alteration) of the host rock. While the dimensions of fault damage zones defined by fracture intensity is beginning to be better understood, how such dimensions compare to the size of alteration zones is less well known. Here, we show quantitative structural and chemical analyses as a function of distance from a crustal-scale strike-slip fault in the Atacama Fault System, Northern Chile, to compare fault damage zone characteristics with its geochemical signature. The Jorgillo Fault (JF) is a ca. 18 km long NNW striking strike-slip fault cutting Mesozoic rocks with sinistral displacement of ca. 4 km. In the study area, the JF cuts through orthogranulitic and gabbroic rocks at the west (JFW) and the east side (JFE), respectively. A 200 m fault perpendicular transect was mapped and sampled for structural and XRF analyses of the core, damage zone and protolith. The core zone consists of a ca. 1 m wide cataclasite zone bounded by two fault gouge zones ca. 40 cm. The damage zone width defined by fracture density is ca. 50 m wide each side of the core. The damage zone in JFW is characterized by NW-striking subvertical 2 cm wide cataclastic rocks and NE-striking milimetric open fractures. In JFE, 1-20 mm wide chlorite, quartz-epidote and quartz-calcite veins, cut the gabbro. Microfracture analysis in JFW reveal mm-wide cataclasitic/ultracataclasitic bands with clasts of protolith and chlorite orientated subparallel to the JF in the matrix, calcite veins in a T-fractures orientation, and minor polidirectional chlorite veins. In JFE, chlorite filled conjugate fractures with syntaxial growth textures and evidence for dilational fracturing processes are seen. Closest to the core, calcite veins crosscut chlorite veins. Whole-rock XRF analyses show Al and Ca content decrease with increasing Si, whereas Na increases towards the core. This can be interpreted as compositional changes of plagioclase to albite-rich ones due to chloritic-propylitic alteration. In the damage zone, LOI increases towards the core but decreases inside of it. This is explained by H2O-rich clays and gypsum in the fault core boundary represented as fault gouge zones whereas in the cataclastic core zone, the decrease in LOI is explained by epidote. Our results show the JF had an evolving permeability structure where a cataclasite-rich core is formed at an early stage, and then a gouge-bounded core is developed which acted as a barrier to fluid from east to west of the fault.

A three-dimensional `Kaiser damage-memory' effect through true-triaxial loading

NASA Astrophysics Data System (ADS)

Meredith, P. G.; Browning, J.; Harland, S. R.; Healy, D.; Stuart, C.; Mitchell, T. M.

2017-12-01

Microcrack damage leading to failure in rocks evolves in response to differential loading. The vast majority of experimental studies investigate damage evolution, the `Kaiser damage-memory' effect, and rock failure using conventional triaxial stress states (σ1 > σ2 = σ3). Such stress states develop a crack population that displays cylindrical transverse isotropy. However, in nature the stress state is in general truly triaxial (σ1 > σ2 > σ3) and experiments that utilise such loading conditions can generate crack populations that display planar transverse isotropy which in turn influences properties such as permeability and strength. We investigate the evolution of crack damage under both conventional and true triaxial stress conditions using results from measurements made on cubic samples of sandstone deformed in three orthogonal directions with independently controlled stress paths. We have measured, simultaneously with stress and strain, the changes in ultrasonic compressional and shear wave velocities in the three principal directions, together with the bulk acoustic emission (AE) output. Changes in acoustic wave velocities are associated with both elastic closure and opening of pre-existing cracks, and the inelastic formation of new cracks. By contrast, AE is only associated with the inelastic growth of new crack damage and as such, we use the onset of AE to determine the initiation of new crack damage. By mapping these damage onsets under both conventional triaxial and true triaxial sequential cyclic loading, we have shown that `damage envelopes' evolve dynamically and can be pushed closer to the failure envelope. Whether a stress state has been `visited' before is key to determining and understanding damage states. Crack damage populations can be generated with multiple orientations depending on the arrangement of loading directions and hence principal stress directions. The sequential cyclic loading tests show that further damage in any one population commences only when the previous maximum differential stress `seen' by that population is exceeded. Understanding anisotropic damage is important for applying the results of true-triaxial tests and hence better replicating natural fractured systems.

Effects of microbeam radiation therapy on normal and tumoral blood vessels.

PubMed

Bouchet, Audrey; Serduc, Raphäel; Laissue, Jean Albert; Djonov, Valentin

2015-09-01

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels. The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT. Copyright © 2015. Published by Elsevier Ltd.

Anti-MRSA activity of isoplagiochin-type macrocyclic bis(bibenzyl)s is mediated through cell membrane damage.

PubMed

Onoda, Kenji; Sawada, Hiromi; Morita, Daichi; Fujii, Kana; Tokiwa, Hiroaki; Kuroda, Teruo; Miyachi, Hiroyuki

2015-07-01

We synthesized three geometrical isomers of a macrocyclic bis(bibenzyl) based on isoplagiochin, a natural product isolated from bryophytes, and evaluated their antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). The isomer containing a 1,4-linked ring (5) showed only weak activity, whereas the isomers containing a 1,3-linked (6) or 1,2-linked (7) C ring showed potent anti-MRSA activity. Molecular dynamics calculations indicated that these differences are probably due to differences in the conformational flexibility of the macrocyclic ring; the active compounds 6 and 7 were more rigid than 5. In order to understand the action mechanism of anti-MRSA activity, we investigated the cellular flux of a fluorescent DNA-binder, ethidium bromide (EtBr), in the presence and absence of these macrocycles. The active compound 6 increased the levels of EtBr inflow and outflow in S. aureus cells, as did our potent anti-MRSA riccardin derivative (4), indicating that these compounds increased the permeability of the cytoplasmic membrane. Inactive 5 had no effect on EtBr inflow or outflow. Furthermore, compound 6 abrogated the normal intracellular concentration gradients of Na(+) and K(+) in S. aureus cells, increasing the intracellular Na(+) concentration and decreasing the K(+) concentration, while 5 had no such effect. These results indicate that anti-MRSA-active macrocyclic bis(bibenzyl) derivatives directly damage the gram-positive bacterial membrane, resulting in increased permeability. Copyright © 2015 Elsevier Ltd. All rights reserved.

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy

PubMed Central

Wong, Philip; Leppert, Ilana R.; Roberge, David; Boudam, Karim; Brown, Paul D.; Muanza, Thierry; Pike, G. Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-01-01

Purpose This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). Method 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Results Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. Conclusions DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages. PMID:27248467

Lacking applicability of in vitro eye irritation methods to identify seriously eye irritating agrochemical formulations: Results of bovine cornea opacity and permeability assay, isolated chicken eye test and the EpiOcular™ ET-50 method to classify according to UN GHS.

PubMed

Kolle, Susanne N; Van Cott, Andrew; van Ravenzwaay, Bennard; Landsiedel, Robert

2017-04-01

In vitro methods have gained regulatory acceptance for the prediction of serious eye damage (UN GHS Cat 1). However, the majority of in vitro methods do not state whether they are applicable to agrochemical formulations. This manuscript presents a study of up to 27 agrochemical formulations tested in three in vitro assays (three versions of the bovine corneal opacity and permeability test (BCOP, OECD TG 437) assay, the isolated chicken eye test (ICE, OECD TG 438) and the EpiOcular™ ET-50 assay). The results were compared with already-available in vivo data. In the BCOP only one of the four, one of five in the ICE and six of eleven tested formulations in the EpiOcular™ ET-50 Neat Protocol resulted in the correct UN GHS Cat 1 prediction. Overpredictions occurred in all assays. These data indicate a lack of applicability of the three in vitro methods to reliably predict UN GHS Cat 1 of agrochemical formulations. In order to ensure animal-free identification of seriously eye damaging agrochemical formulations testing protocols and/or prediction models need to be modified or classification rules should be tailored to in vitro testing rather than using in vivo Draize data as a standard. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Airway Obstruction Due to Bronchial Vascular Injury after Sulfur Mustard Analog Inhalation

PubMed Central

Veress, Livia A.; O'Neill, Heidi C.; Hendry-Hofer, Tara B.; Loader, Joan E.; Rancourt, Raymond C.; White, Carl W.

2010-01-01

Rationale: Sulfur mustard (SM) is a frequently used chemical warfare agent, even in modern history. SM inhalation causes significant respiratory tract injury, with early complications due to airway obstructive bronchial casts, akin to those seen after smoke inhalation and in single-ventricle physiology. This process with SM is poorly understood because animal models are unavailable. Objectives: To develop a rat inhalation model for airway obstruction with the SM analog 2-chloroethyl ethyl sulfide (CEES), and to investigate the pathogenesis of bronchial cast formation. Methods: Adult rats were exposed to 0, 5, or 7.5% CEES in ethanol via nose-only aerosol inhalation (15 min). Airway microdissection and confocal microscopy were used to assess cast formation (4 and 18 h after exposure). Bronchoalveolar lavage fluid (BALF) retrieval and intravascular dye injection were done to evaluate vascular permeability. Measurements and Main Results: Bronchial casts, composed of abundant fibrin and lacking mucus, occluded dependent lobar bronchi within 18 hours of CEES exposure. BALF contained elevated concentrations of IgM, protein, and fibrin. Accumulation of fibrin-rich fluid in peribronchovascular regions (4 h) preceded cast formation. Monastral blue dye leakage identified bronchial vessels as the site of leakage. Conclusions: After CEES inhalation, increased permeability from damaged bronchial vessels underlying damaged airway epithelium leads to the appearance of plasma proteins in both peribronchovascular regions and BALF. The subsequent formation of fibrin-rich casts within the airways then leads to airways obstruction, causing significant morbidity and mortality acutely after exposure. PMID:20639443

Concentration gradient along the scala tympani after local application of gentamicin to the round window membrane.

PubMed

Plontke, Stefan K; Mynatt, Robert; Gill, Ruth M; Borgmann, Stefan; Salt, Alec N

2007-07-01

The distribution of gentamicin along the fluid spaces of the cochlea after local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected, and histologic studies indicate that hair cell damage is greater at the base than at the apex after local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. A recently developed method of sampling perilymph from the cochlear apex of guinea pigs was used in which the samples represent fluid originating from different regions along the scala tympani. Gentamicin concentration was determined in sequential apical samples that were taken after up to 3 hours of local application to the round window niche. Substantial gradients of gentamicin along the length of the scala tympani were demonstrated and quantified, averaging more than 4,000 times greater concentration at the base compared with the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients.

Concentration gradient along scala tympani following the local application of gentamicin to the round window membrane

PubMed Central

Plontke, Stefan K.; Mynatt, Robert; Gill, Ruth M.; Borgmann, Stefan; Salt, Alec N.

2008-01-01

Objectives The distribution of gentamicin along the fluid spaces of the cochlea following local applications has never previously been demonstrated. Computer simulations have predicted that significant basal-apical concentration gradients might be expected and histological studies indicate that hair cell damage is greater at the base than at the apex following local gentamicin application. In the present study, gradients of gentamicin along the cochlea were measured. Methods A recently-developed method of sampling perilymph from the cochlear apex of guinea pigs was used, in which the samples represent fluid originating from different regions along scala tympani. Gentamicin concentration was determined in sequential apical samples which were taken following up to three hours of local application to the round window niche. Results Substantial gradients of gentamicin along the length of scala tympani were demonstrated and quantified, averaging more than 4000 times greater concentration at the base compared to the apex at the time of sampling. Peak concentrations and gradients for gentamicin varied considerably between animals, likely resulting from variations in round window membrane permeability and rates of perilymph flow. Conclusions The large gradients for gentamicin demonstrated here in guinea pigs account for how it is possible to suppress vestibular function in some patients with a local application of gentamicin without damaging auditory function. Variations in round window membrane permeability and in perilymph flow could account for why hearing losses are observed in some patients. PMID:17603318

Visualizing the Acute Effects of Vascular-Targeted Therapy In Vivo Using Intravital Microscopy and Magnetic Resonance Imaging: Correlation with Endothelial Apoptosis, Cytokine Induction, and Treatment Outcome1

PubMed Central

Seshadri, Mukund; Spernyak, Joseph A; Maiery, Patricia G; Cheney, Richard T; Mazurchuk, Richard; Bellnier, David A

2007-01-01

Abstract The acute effects of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) were investigated in vivo using intravital microscopy (IVM) and magnetic resonance imaging (MRI). Changes in vascular permeability and blood flow of syngeneic CT-26 murine colon adenocarcinomas were assessed at 4 and 24 hours after DMXAA treatment (30 mg/kg, i.p.) and correlated with induction of tumor necrosis factor-α (TNF-α), endothelial damage [CD31/terminal deoxynucleotidyl transferase (TdT)], and treatment outcome. Intravital imaging revealed a marked increase in vascular permeability 4 hours after treatment, consistent with increases in intratumoral mRNA and protein levels of TNF-α. Parallel contrast-enhanced MRI studies showed a ∼ 4-fold increase in longitudinal relaxation rates (ΔR1), indicative of increased contrast agent accumulation within the tumor. Dual immunostained tumor sections (CD31/TdT) revealed evidence of endothelial apoptosis at this time point. Twenty-four hours after treatment, extensive hemorrhage and complete disruption of vascular architecture were observed with IVM, along with a significant reduction in ΔR1; and virtual absence of CD31 immunostaining. DMXAA-induced tumor vascular damage resulted in significant long-term (60-day) cures compared to untreated controls. Multimodality imaging approaches are useful in visualizing the effects of antivascular therapy in vivo. Such approaches allow cross validation and correlation of findings with underlying molecular changes contributing to treatment outcome. PMID:17356709

A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.

PubMed

Wong, Philip; Leppert, Ilana R; Roberge, David; Boudam, Karim; Brown, Paul D; Muanza, Thierry; Pike, G Bruce; Chankowsky, Jeffrey; Mihalcioiu, Catalin

2016-08-09

This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Regulation and function of endothelial glycocalyx layer in vascular diseases.

PubMed

Sieve, Irina; Münster-Kühnel, Anja K; Hilfiker-Kleiner, Denise

2018-01-01

In the vascular system, the endothelial surface layer (ESL) as the inner surface of blood vessels affects mechanotransduction, vascular permeability, rheology, thrombogenesis, and leukocyte adhesion. It creates barriers between endothelial cells and blood and neighbouring cells. The glycocalyx, composed of glycoconjugates and proteoglycans, is an integral component of the ESL and a key element in inter- and intracellular communication and tissue homeostasis. In pathophysiological conditions (atherosclerosis, infection, ischemia/reperfusion injury, diabetes, trauma and acute lung injury) glycocalyx-degrading factors, i.e. reactive oxygen and nitrogen species, matrix metalloproteinases, heparanase and sialidases, damage the ESL, thereby impairing endothelial functions. This leads to increased capillary permeability, leucocyte-endothelium interactions, thrombosis and vascular inflammation, the latter further driving glycocalyx destruction. The present review highlights current knowledge on the vasculoprotective role of the ESL, with specific emphasis on its remodelling in inflammatory vascular diseases and discusses its potential as a novel therapeutic target to treat vascular pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurovascular unit impairment in early Alzheimer's disease measured with magnetic resonance imaging.

PubMed

van de Haar, Harm J; Jansen, Jacobus F A; van Osch, Matthias J P; van Buchem, Mark A; Muller, Majon; Wong, Sau May; Hofman, Paul A M; Burgmans, Saartje; Verhey, Frans R J; Backes, Walter H

2016-09-01

The neurovascular unit, which protects neuronal cells and supplies them with essential molecules, plays an important role in the pathophysiology of Alzheimer's Disease (AD). The aim of this study was to noninvasively investigate 2 linked functional elements of the neurovascular unit, blood-brain barrier (BBB) permeability and cerebral blood flow (CBF), in patients with early AD and healthy controls. Therefore, both dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling magnetic resonance imaging were applied to measure BBB permeability and CBF, respectively. The patients with early AD showed significantly lower CBF and local blood volume in the gray matter, compared with controls. In the patients, we also found that a reduction in CBF is correlated with an increase in leakage rate. This finding supports the hypothesis that neurovascular damage, and in particular impairment of the neurovascular unit constitutes the pathophysiological link between CBF reduction and BBB impairment in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms.

PubMed

Antonisamy, Paulrayer; Duraipandiyan, Veeramuthu; Aravinthan, Adithan; Al-Dhabi, Naif Abdullah; Ignacimuthu, Savarimuthu; Choi, Ki Choon; Kim, Jong-Hoon

2015-03-05

The current study was aimed to investigate the gastroprotective effects of friedelin isolated from the hexane extract of leaves of Azima tetracantha. Ethanol-induced gastric ulcer model was used to investigate the gastroprotective effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide, gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis level have been investigated. Ethanol caused severe gastric damage and friedelin pretreatment protected against its deleterious role. Antioxidant enzyme activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive nitric oxide synthase (cNOS) and mucus weight have been increased significantly. However, the vascular permeability, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been decreased after friedelin ingestion. The present study has clearly demonstrated the anti-ulcer potential of friedelin, these findings suggested that friedelin could be a new useful natural gastroprotective tool against gastric ulcer. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

González, Rafael I.; Valencia, Felipe; Mella, José

The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role ofmore » nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.« less

Preservative cytotoxic threshold for benzalkonium chloride and chlorhexidine digluconate in cat and rabbit corneas.

PubMed

Burstein, N L

1980-03-01

Benzalkonium chloride (BAC) and chlorhexidine digluconate (CDG) were applied to rabbit and cat corneal epithelium in clinically used concentrations. Corneas were fixed 1/2 hr later and examined by scanning electron microscopy (SEM). BAC was found to produce a progressive increase in damage at concentrations between 0.001% and 0.01% as determined by SEM. CGD produced less damage than BAC at any concentration. Cats lacrimated copiously and blinked frequently after instillation of drops; rabbits did not. No significant difference was found between the two species, however, in their response to the preservative agents tested. It is presumed that binding of these surface active agents occurs almost immediately and is unaffected by tear film dilution. Studies measuring permeability increase in the human eye after preservative use are required to allow clinical interpretation of the data presented here.

The tissue-type plasminogen activator–plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans

PubMed Central

Sashindranath, Maithili; Sales, Eunice; Daglas, Maria; Freeman, Roxann; Samson, Andre L.; Cops, Elisa J.; Beckham, Simone; Galle, Adam; McLean, Catriona; Morganti-Kossmann, Cristina; Rosenfeld, Jeffrey V.; Madani, Rime; Vassalli, Jean-Dominique; Su, Enming J.; Lawrence, Daniel A.

2012-01-01

The neurovascular unit provides a dynamic interface between the circulation and central nervous system. Disruption of neurovascular integrity occurs in numerous brain pathologies including neurotrauma and ischaemic stroke. Tissue plasminogen activator is a serine protease that converts plasminogen to plasmin, a protease that dissolves blood clots. Besides its role in fibrinolysis, tissue plasminogen activator is abundantly expressed in the brain where it mediates extracellular proteolysis. However, proteolytically active tissue plasminogen activator also promotes neurovascular disruption after ischaemic stroke; the molecular mechanisms of this process are still unclear. Tissue plasminogen activator is naturally inhibited by serine protease inhibitors (serpins): plasminogen activator inhibitor-1, neuroserpin or protease nexin-1 that results in the formation of serpin:protease complexes. Proteases and serpin:protease complexes are cleared through high-affinity binding to low-density lipoprotein receptors, but their binding to these receptors can also transmit extracellular signals across the plasma membrane. The matrix metalloproteinases are the second major proteolytic system in the mammalian brain, and like tissue plasminogen activators are pivotal to neurological function but can also degrade structures of the neurovascular unit after injury. Herein, we show that tissue plasminogen activator potentiates neurovascular damage in a dose-dependent manner in a mouse model of neurotrauma. Surprisingly, inhibition of activity following administration of plasminogen activator inhibitor-1 significantly increased cerebrovascular permeability. This led to our finding that formation of complexes between tissue plasminogen activator and plasminogen activator inhibitor-1 in the brain parenchyma facilitates post-traumatic cerebrovascular damage. We demonstrate that following trauma, the complex binds to low-density lipoprotein receptors, triggering the induction of matrix metalloproteinase-3. Accordingly, pharmacological inhibition of matrix metalloproteinase-3 attenuates neurovascular permeability and improves neurological function in injured mice. Our results are clinically relevant, because concentrations of tissue plasminogen activator: plasminogen activator inhibitor-1 complex and matrix metalloproteinase-3 are significantly elevated in cerebrospinal fluid of trauma patients and correlate with neurological outcome. In a separate study, we found that matrix metalloproteinase-3 and albumin, a marker of cerebrovascular damage, were significantly increased in brain tissue of patients with neurotrauma. Perturbation of neurovascular homeostasis causing oedema, inflammation and cell death is an important cause of acute and long-term neurological dysfunction after trauma. A role for the tissue plasminogen activator–matrix metalloproteinase axis in promoting neurovascular disruption after neurotrauma has not been described thus far. Targeting tissue plasminogen activator: plasminogen activator inhibitor-1 complex signalling or downstream matrix metalloproteinase-3 induction may provide viable therapeutic strategies to reduce cerebrovascular permeability after neurotrauma. PMID:22822039

Glutamine supplementation, but not combined glutamine and arginine supplementation, improves gut barrier function during chemotherapy-induced intestinal mucositis in rats.

PubMed

Beutheu, Stéphanie; Ouelaa, Wassila; Guérin, Charlène; Belmonte, Liliana; Aziz, Moutaz; Tennoune, Naouel; Bôle-Feysot, Christine; Galas, Ludovic; Déchelotte, Pierre; Coëffier, Moïse

2014-08-01

Increased intestinal permeability occurs during chemotherapy-induced intestinal mucositis. Previous data suggest that glutamine and arginine may have additive or synergic effects to limit intestinal damage. The present study aimed to evaluate the effects of glutamine and arginine, each alone or in combination, on gut barrier function during methotrexate (MTX)-induced mucositis in rats. Eighty Sprague Dawley rats received during 7 days (d) standard chow supplemented with protein powder (PP), glutamine (G, 2%), arginine (A, 1.2%) or glutamine plus arginine (GA). All diets were isonitrogenous. Rats received subcutaneous injections of MTX (2.5 mg/kg) from d0 to d2. The intestinal permeability and tight junction proteins were assessed at d4 and d9 in the jejunum by FITC-dextran and by western blot and immunohistochemistry, respectively. At d4, intestinal permeability was increased in MTX-PP, MTX-A and MTX-GA rats compared with controls but not in MTX-G rats. The expression of claudin-1, occludin and ZO-1 was decreased in MTX-PP group compared with controls but was restored in MTX-G and MTX-A rats. In MTX-GA rats, occludin expression remained decreased. These effects could be explained by an increase of erk phosphorylation and a decrease of IκBα expression in MTX-PP and MTX-GA rats. At d9, Intestinal permeability remained higher only in MTX-GA rats. This was associated with a persistent decrease of occludin expression. Glutamine prevents MTX-induced gut barrier disruption by regulating occludin and claudin-1 probably through erk and NF-κB pathways. In contrast, combined glutamine and arginine has no protective effect in this model. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Coral larvae conservation: physiology and reproduction.

PubMed

Hagedorn, M; Pan, R; Cox, E F; Hollingsworth, L; Krupp, D; Lewis, T D; Leong, J C; Mazur, P; Rall, W F; MacFarlane, D R; Fahy, G; Kleinhans, F W

2006-02-01

Coral species throughout the world's oceans are facing severe environmental pressures. We are interested in conserving coral larvae by means of cryopreservation, but little is known about their cellular physiology or cryobiology. These experiments examined cryoprotectant toxicity, dry weight, water and cryoprotectant permeability using cold and radiolabeled glycerol, spontaneous ice nucleation temperatures, chilling sensitivity, and settlement of coral larvae. Our two test species of coral larvae, Pocillopora damicornis (lace coral), and Fungia scutaria (mushroom coral) demonstrated a wide tolerance to cryoprotectants. Computer-aided morphometry determined that F. scutaria larvae were smaller than P. damicornis larvae. The average dry weight for P. damicornis was 24.5%, while that for F. scutaria was 17%, yielding osmotically inactive volumes (V(b)) of 0.22 and 0.15, respectively. The larvae from both species demonstrated radiolabeled glycerol uptake over time, suggesting they were permeable to the glycerol. Parameter fitting of the F. scutaria larvae data yielded a water permeability 2 microm/min/atm and a cryoprotectant permeability = 2.3 x 10(-4) cm/min while modeling indicated that glycerol reached 90% of final concentration in the larvae within 25 min. The spontaneous ice nucleation temperature for F. scutaria larvae in filtered seawater was -37.8+/-1.4 degrees C. However, when F. scutaria larvae were chilled from room temperature to -11 degrees C at various rates, they exhibited 100% mortality. When instantly cooled from room temperature to test temperatures, they showed damage below 10 degrees C. These data suggest that they are sensitive to both the rate of chilling and the absolute temperature, and indicate that vitrification may be the only means to successfully cryopreserve these organisms. Without prior cryopreservation, both species of coral settled under laboratory conditions.

Inhalation of methane preserves the epithelial barrier during ischemia and reperfusion in the rat small intestine.

PubMed

Mészáros, András T; Büki, Tamás; Fazekas, Borbála; Tuboly, Eszter; Horváth, Kitti; Poles, Marietta Z; Szűcs, Szilárd; Varga, Gabriella; Kaszaki, József; Boros, Mihály

2017-06-01

Methane is part of the gaseous environment of the intestinal lumen. The purpose of this study was to elucidate the bioactivity of exogenous methane on the intestinal barrier function in an antigen-independent model of acute inflammation. Anesthetized rats underwent sham operation or 45-min occlusion of the superior mesenteric artery. A normoxic methane (2.2%)-air mixture was inhaled for 15 min at the end of ischemia and at the beginning of a 60-min or 180-min reperfusion. The integrity of the epithelial barrier of the ileum was assessed by determining the lumen-to-blood clearance of fluorescent dextran, while microvascular permeability changes were detected by the Evans blue technique. Tissue levels of superoxide, nitrotyrosine, myeloperoxidase, and endothelin-1 were measured, the superficial mucosal damage was visualized and quantified, and the serosal microcirculation and mesenteric flow was recorded. Erythrocyte deformability and aggregation were tested in vitro. Reperfusion significantly increased epithelial permeability, worsened macro- and microcirculation, increased the production of proinflammatory mediators, and resulted in a rapid loss of the epithelium. Exogenous normoxic methane inhalation maintained the superficial mucosal structure, decreased epithelial permeability, and improved local microcirculation, with a decrease in reactive oxygen and nitrogen species generation. Both the deformability and aggregation of erythrocytes improved with incubation of methane. Normoxic methane decreases the signs of oxidative and nitrosative stress, improves tissue microcirculation, and thus appears to modulate the ischemia-reperfusion-induced epithelial permeability changes. These findings suggest that the administration of exogenous methane may be a useful strategy for maintaining the integrity of the mucosa sustaining an oxido-reductive attack. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage.

PubMed

Klar, Joakim; Piontek, Jörg; Milatz, Susanne; Tariq, Muhammad; Jameel, Muhammad; Breiderhoff, Tilman; Schuster, Jens; Fatima, Ambrin; Asif, Maria; Sher, Muhammad; Mäbert, Katrin; Fromm, Anja; Baig, Shahid M; Günzel, Dorothee; Dahl, Niklas

2017-07-01

Claudins constitute the major component of tight junctions and regulate paracellular permeability of epithelia. Claudin-10 occurs in two major isoforms that form paracellular channels with ion selectivity. We report on two families segregating an autosomal recessive disorder characterized by generalized anhidrosis, severe heat intolerance and mild kidney failure. All affected individuals carry a rare homozygous missense mutation c.144C>G, p.(N48K) specific for the claudin-10b isoform. Immunostaining of sweat glands from patients suggested that the disease is associated with reduced levels of claudin-10b in the plasma membranes and in canaliculi of the secretory portion. Expression of claudin-10b N48K in a 3D cell model of sweat secretion indicated perturbed paracellular Na+ transport. Analysis of paracellular permeability revealed that claudin-10b N48K maintained cation over anion selectivity but with a reduced general ion conductance. Furthermore, freeze fracture electron microscopy showed that claudin-10b N48K was associated with impaired tight junction strand formation and altered cis-oligomer formation. These data suggest that claudin-10b N48K causes anhidrosis and our findings are consistent with a combined effect from perturbed TJ function and increased degradation of claudin-10b N48K in the sweat glands. Furthermore, affected individuals present with Mg2+ retention, secondary hyperparathyroidism and mild kidney failure that suggest a disturbed reabsorption of cations in the kidneys. These renal-derived features recapitulate several phenotypic aspects detected in mice with kidney specific loss of both claudin-10 isoforms. Our study adds to the spectrum of phenotypes caused by tight junction proteins and demonstrates a pivotal role for claudin-10b in maintaining paracellular Na+ permeability for sweat production and kidney function.

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

PubMed Central

Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid.

PubMed

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L

2015-01-01

Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. Copyright © 2015 International Society for Peritoneal Dialysis.

Alterations of Intercellular Junctions in Peritoneal Mesothelial Cells from Patients Undergoing Dialysis: Effect of Retinoic Acid

PubMed Central

Retana, Carmen; Sanchez, Elsa; Perez-Lopez, Alejandro; Cruz, Armando; Lagunas, Jesus; Cruz, Carmen; Vital, Socorro; Reyes, Jose L.

2015-01-01

♦ Background: Dialysis patients are classified according to their peritoneal permeability as low transporter (LT, low solute permeability) or high transporter (HT, high solute permeability). Tight junction (TJ) proteins are critical to maintain ions, molecules and water paracellular transport through peritoneum. Exposure to peritoneal dialysis solutions causes damage to TJ in human peritoneal mesothelial cells (HPMCs). We analyzed the quantity, distribution and function of TJ proteins: claudin-1, -2 and -8, ZO-1 and occludin, in HPMC cultures from LT and HT patients. Since all-trans retinoic acid (ATRA) might modify the expression of TJ proteins, we studied its effect on HPMCs. ♦ Methods: Control HPMCs were isolated from human omentum, while HT or LT cells were obtained from dialysis effluents. Cells were cultured in presence of ATRA 0, 50 or 100 nM. Transepithelial electrical resistance (TER) measurement, immunostaining and Western blot analyses were performed. ♦ Results: HT exhibited lower TER than control and LT monolayers. Immunofluorescence for TJ was weak and discontinuous along the cell contour, in LT and HT. Furthermore, claudin-1, occludin and ZO-1 expressions were decreased. In all groups, claudin-2 was localized at nuclei. We observed that ATRA improved TJ distribution and increased TJ expression in HT. This retinoid did not modify claudin-2 and -8 expressions. All-trans retinoic acid decreased TER in HT, but had no effect in LT. ♦ Conclusions: Tight junctions were altered in HPMCs from dialyzed patients. The HT monolayer has lower TER than LT, which might be associated with the peritoneal permeability in these patients. ATRA might be a therapeutic alternative to maintain mesothelial integrity, since it improved TJ localization and expression. PMID:24584604

Non-invasive biomarkers of pulmonary damage and inflammation: Application to children exposed to ozone and trichloramine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, Alfred; Carbonnelle, Sylviane; Nickmilder, Marc

2005-08-07

To date, airways injury or inflammation caused by air pollutants has been evaluated mainly by analysis of bronchoalveolar lavage, an invasive technique totally unsuitable to children. The assessment of respiratory risks in this particularly vulnerable population has thus for a long time relied on spirometric tests and self-reported symptoms which are relatively late and inaccurate indicators of lung damage. Research in the field of biomarkers is now opening new perspectives with the development of non-invasive tests allowing to monitor inflammation and damage in the deep lung. Blood tests measuring lung-specific proteins (pneumoproteins) such as Clara cell protein (CC16) and surfactant-associatedmore » proteins (A, B or D) are now available to evaluate the permeability and/or the cellular integrity of the pulmonary epithelium. The application of these tests to children has recently led to the discovery of a lung epithelium hyperpermeability caused by trichloramine (nitrogen trichloride), an irritant gas contaminating the air of indoor-chlorinated pools. Serum CC16 can also serve to detect increases of airway permeability during short-term exposures to ambient ozone. Indicators measurable in exhaled air such as nitric oxide (NO) appear more useful to detect airway inflammation. By applying the exhaled NO test to children attending summer camps, we recently found that ambient ozone produces an acute inflammatory response in children from levels slightly lower than current air quality guidelines. In a study exploring the links between atopy, asthma, and exposure to chlorination products in indoor pools, we also found that the exhaled NO test can serve to detect the chronic airway inflammation associated with excessive exposure to trichloramine. Lung-specific proteins measurable in serum and markers in exhaled air represent sensitive tools that can be used to assess non-invasively the effects of air pollutants on the respiratory tract of children.« less

Insulin differentially affects the distribution kinetics of amyloid beta 40 and 42 in plasma and brain.

PubMed

Swaminathan, Suresh Kumar; Ahlschwede, Kristen M; Sarma, Vidur; Curran, Geoffry L; Omtri, Rajesh S; Decklever, Teresa; Lowe, Val J; Poduslo, Joseph F; Kandimalla, Karunya K

2018-05-01

Impaired brain clearance of amyloid-beta peptides (Aβ) 40 and 42 across the blood-brain barrier (BBB) is believed to be one of the pathways responsible for Alzheimer's disease (AD) pathogenesis. Hyperinsulinemia prevalent in type II diabetes was shown to damage cerebral vasculature and increase Aβ accumulation in AD brain. However, there is no clarity on how aberrations in peripheral insulin levels affect Aβ accumulation in the brain. This study describes, for the first time, an intricate relation between plasma insulin and Aβ transport at the BBB. Upon peripheral insulin administration in wild-type mice: the plasma clearance of Aβ40 increased, but Aβ42 clearance reduced; the plasma-to-brain influx of Aβ40 increased, and that of Aβ42 reduced; and the clearance of intracerebrally injected Aβ40 decreased, whereas Aβ42 clearance increased. In hCMEC/D3 monolayers (in vitro BBB model) exposed to insulin, the luminal uptake and luminal-to-abluminal permeability of Aβ40 increased and that of Aβ42 reduced; the abluminal-to-luminal permeability of Aβ40 decreased, whereas Aβ42 permeability increased. Moreover, Aβ cellular trafficking machinery was altered. In summary, Aβ40 and Aβ42 demonstrated distinct distribution kinetics in plasma and brain compartments, and insulin differentially modulated their distribution. Cerebrovascular disease and metabolic disorders may disrupt this intricate homeostasis and aggravate AD pathology.

Biophysical studies of photosystem II-related recovery processes after a heat pulse in barley seedlings (Hordeum vulgare L.).

PubMed

Tóth, Szilvia Z; Schansker, Gert; Kissimon, Judit; Kovács, László; Garab, Gyozo; Strasser, Reto J

2005-02-01

Leaves of 7-day-old barley seedlings were subjected to heat pulses at 50 degrees C for 20 or 40s to inhibit partially or fully the oxygen evolution without inducing visible symptoms. By means of biophysical techniques, we investigated the time course and mechanism of photosystem II (PSII) recovery. After the heat treatment, the samples were characterized by typical heat stress symptoms: loss of oxygen evolution activity, strong decrease of Fv/Fm, induction of the K-step in the fluorescence induction transient, emergence of the AT-thermoluminescence-band and a dramatic increase in membrane permeability. In the first 4h in the light following the heat pulse, the AT-band and the K-step disappeared in parallel, indicating the loss of this restricted activity of PSII. This phase was followed by a recovery period, during which PSII-activity was gradually restored in the light. In darkness, no recovery, except for the membrane permeability, was observed. A model is presented that accounts for (i) the damage induced by the heat pulse on the membrane architecture and on the PSII donor side, (ii) the light-dependent removal of the impaired reaction centers from the disorganized membrane, and (iii) the subsequent light-independent restoration of the membrane permeability and the de novo synthesis of the PSII reaction centers in the light.

Heterogeneity of the calcium-induced permeability transition in isolated non-synaptic brain mitochondria.

PubMed

Kristián, Tibor; Weatherby, Tina M; Bates, Timothy E; Fiskum, Gary

2002-12-01

Calcium overload of neural cell mitochondria plays a key role in excitotoxic and ischemic brain injury. This study tested the hypothesis that brain mitochondria consist of subpopulations with differential sensitivity to calcium-induced inner membrane permeability transition, and that this sensitivity is greatly reduced by physiological levels of adenine nucleotides. Isolated non-synaptosomal rat brain mitochondria were incubated in a potassium-based medium in the absence or presence of ATP or ADP. Measurements were made of medium and intramitochondrial free calcium, light scattering, mitochondrial ultrastructure, and the elemental composition of electron-opaque deposits within mitochondria treated with calcium. In the absence of adenine nucleotides, calcium induced a partial decrease in light scattering, accompanied by three distinct ultrastructural morphologies, including large-amplitude swelling, matrix vacuolization and a normal appearance. In the presence of ATP or ADP the mitochondrial calcium uptake capacity was greatly enhanced and calcium induced an increase rather than a decrease in mitochondrial light scattering. Approximately 10% of the mitochondria appeared damaged and the rest contained electron-dense precipitates that contained calcium, as determined by electron-energy loss spectroscopy. These results indicate that brain mitochondria are heterogeneous in their response to calcium. In the absence of adenine nucleotides, approximately 20% of the mitochondrial population exhibit morphological alterations consistent with activation of the permeability transition, but less than 10% exhibit evidence of osmotic swelling and membrane disruption in the presence of ATP or ADP.

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

PubMed

Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

2009-09-18

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.

Effect of mechanical cleaning with granular material on the permeability of submerged membranes in the MBR process.

PubMed

Siembida, B; Cornel, P; Krause, S; Zimmermann, B

2010-07-01

The research on fouling reduction and permeability loss in membrane bioreactors (MBRs) was carried out at two MBR pilot plants with synthetic and real wastewater. On the one hand, the effect of mechanical cleaning with an abrasive granular material on the performance of a submerged MBR process was tested. Additionally, scanning electron microscopy (SEM) measurements and integrity tests were conducted to check whether the membrane material was damaged by the granulate.The results indicate that the fouling layer formation was significantly reduced by abrasion using the granular material. This technique allowed a long-term operation of more than 600 days at a flux up to 40 L/(m2 h) without chemical cleaning of the membranes. Moreover, it was demonstrated that the membrane bioreactor (MBR) with granulate could be operated with more than 20% higher flux compared to a conventional MBR operation. SEM images and integrity tests showed that in consequence of abrasive cleaning, the granular material left brush marks on the membrane surface, however, the membrane function was not affected.In a parallel experimental set up, the impact of the operationally defined "truly soluble fraction" <0.04 microm from wastewater and activated sludge on the ultrafiltration membrane fouling characteristics was investigated. It was shown that the permeability loss was caused predominantly by the colloidal fraction >0.04 microm rather than by the dissolved fraction of wastewater and activated sludge.

Physical and Transport Properties of the carbonate-bearing faults: experimental insights from the Monte Maggio Fault zone (Central Italy)

NASA Astrophysics Data System (ADS)

Trippetta, Fabio; Scuderi, Marco Maria; Collettini, Cristiano

2015-04-01

Physical properties of fault zones vary with time and space and in particular, fluid flow and permeability variations are strictly related to fault zone processes. Here we investigate the physical properties of carbonate samples collected along the Monte Maggio normal Fault (MMF), a regional structure (length ~10 km and displacement ~500 m) located within the active system of the Apennines. In particular we have studied an exceptionally exposed outcrop of the fault within the Calcare Massiccio formation (massive limestone) that has been recently exposed by new roadworks. Large cores (100 mm in diameter and up to 20 cm long) drilled perpendicular to the fault plane have been used to: 1) characterize the damage zone adjacent to the fault plane and 2) to obtain smaller cores, 38 mm in diameter both parallel and perpendicular to the fault plane, for rock deformation experiments. At the mesoscale two types of cataclastic damage zones can be identified in the footwall block (i) a Cemented Cataclasite (CC) and (ii), a Fault Breccia (FB). Since in some portions of the fault the hangingwall (HW) is still preserved we also collected HW samples. After preliminary porosity measurements at ambient pressure, we performed laboratory measurements of Vp, Vs, and permeability at effective confining pressures up to 100 MPa in order to simulate crustal conditions. The protolith has a primary porosity of about 7 %, formed predominantly by isolated pores since the connected porosity is only 1%. FB samples are characterized by 10% and 5% of bulk and connected porosity respectively, whilst CC samples show lower bulk porosity (7%) and a connected porosity of 2%. From ambient pressure to 100 MPa, P-wave velocity is about 5,9-6,0 km/s for the protolith, ranges from 4,9 km/s to 5,9 km/s for FB samples, whereas it is constant at 5,9 km/s for CC samples and ranges from 5,4 to 5,7 for HW sample. Vs shows the same behaviour resulting in a constant Vp/Vs ratio from 0 to 100 MPa that ranges from 1,5 to 1,98 where the lower values are recorded for FB samples. Permeability of FB samples is pressure dependent starting from 10-17 m2 at ambient pressure to 10-18 m2 at 100 MPa confining pressure. In contrast, for CC samples, permeability is about 10-19 m2 and is pressure independent. In conclusion, our dataset depicts a fault zone structure with heterogeneous static physical and transport properties that are controlled by the occurrence of different deformation mechanisms related to different protolites. At the moment we have been conducting experiments during loading/unloading stress cycles in order to characterize possible permeability and acoustic properties evolution induced by differential stress.

The effect of retinol on the hyperthermal response of normal tissue in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rogers, M.A.; Marigold, J.C.; Hume, S.P.

The effect of prior administration of retinol, a membrane labilizer, on the in vivo hyperthermal response of lysosomes was investigated in the mouse spleen using a quantitative histochemical assay for the lysosomal enzyme acid phosphatase. A dose of retinol which had no effect when given alone enhanced the thermal response of the lysosome, causing an increase in lysosomal membrane permeability. In contrast, the same dose of retinol had no effect on the gross hyperthermal response of mouse intestine; a tissue which is relatively susceptible to hyperthermia. Thermal damage to intestine was assayed directly by crypt loss 1 day after treatmentmore » or assessed as thermal enhancement of X-ray damage by counting crypt microcolonies 4 days after a combined heat and X-ray treatment. Thus, although the hyperthermal response of the lysosome could be enhanced by the administration of retinol, thermal damage at a gross tissue level appeared to be unaffected, suggesting that lysosomal membrane injury is unlikely to be a primary event in hyperthermal cell killing.« less

Resurfacing Damaged Articular Cartilage to Restore Compressive Properties

PubMed Central

Grenier, Stephanie; Donnelly, Patrick E.; Gittens, Jamila; Torzilli, Peter A.

2014-01-01

Surface damage to articular cartilage is recognized as the initial underlying process causing the loss of mechanical function in early-stage osteoarthritis. In this study, we developed structure-modifying treatments to potentially prevent, stabilize or reverse the loss in mechanical function. Various polymers (chondroitin sulfate, carboxymethylcellulose, sodium hyaluronate) and photoinitiators (riboflavin, irgacure 2959) were applied to the surface of collagenase-degraded cartilage and crosslinked in situ using UV light irradiation. While matrix permeability and deformation significantly increased following collagenase-induced degradation of the superficial zone, resurfacing using tyramine-substituted sodium hyaluronate and riboflavin decreased both values to a level comparable to that of intact cartilage. Repetitive loading of resurfaced cartilage showed minimal variation in the mechanical response over a 7 day period. Cartilage resurfaced using a low concentration of riboflavin had viable cells in all zones while a higher concentration resulted in a thin layer of cell death in the uppermost superficial zone. Our approach to repair surface damage initiates a new therapeutic advance in the treatment of injured articular cartilage with potential benefits that include enhanced mechanical properties, reduced susceptibility to enzymatic degradation and reduced adhesion of macrophages. PMID:25468298

Effect of Synthetic Matrix Metalloproteinase Inhibitors on Lipopolysaccharide-Induced Blood-Brain Barrier Opening in Rodents: Differences in Response Based on Strains and Solvents

PubMed Central

Rosenberg, Gary A.; Estrada, Eduardo Y.; Mobashery, Shahriar

2007-01-01

Matrix metalloproteinase inhibitors (MMPIs) reduce blood-brain barrier (BBB) disruption and prevent cell death. Animal models of multiple sclerosis, cerebral ischemia and hemorrhage, and bacterial meningitis respond to treatment with MMPIs. We have used the intracerebral injection of lipopolysaccharide (LPS) in rat, which induces MMP production and results in a delayed opening of the BBB, to screen MMPIs to identify therapeutic agents. We hypothesized that the mouse would respond similarly to LPS and that the mouse/LPS model of BBB damage would be more useful for screening of MMPIs. Therefore, we adapted the rat LPS model to the mouse and compared the response to LPS and treatment with MMPIs. Wistar-Kyoto rats (WKY) and three strains of mice had stereotactic injections of LPS into the caudate. 14C-sucrose was used to measure permeability of the BBB 24 hours after injection. Initially, we tested three broad-spectrum MMPIs in the rat, BB-1101, BB-94, and BB-2293, and a MMP-2 selective inhibitor, IW449; both BB-1101 and BB-94 significantly suppressed LPS-induced BBB damage (p<0.05). In the 3 mouse strains, C57/BL6, C57/BL10, and C57/BL10HIIIR2, LPS significantly opened the BBB in C57/BL6, and it was the only strain that showed a reduction in BBB permeability with BB-94. Treatment with methylprednisolone and several broad spectrum MMPIs, including BB-1101, were ineffective in the C57/BL6. There was a significant reduction in BBB permeability seen with 10% dimethyl sulfoxide (DMSO) alone, which was used to dissolve the selective MMP-2 and -9 inhibitor, SB-3CT. The tetracycline derivative, minocycline, reduced the BBB injury in mouse by blocking the production of MMP-9. Our results show variability in rats and mice to LPS and MMPIs, which most likely is based on genetic make-up. Understanding these differences may provide important clues that could guide selection of MMPIs in treatment of neurological diseases. PMID:17184743

Causation by Diesel Exhaust Particles of Endothelial Dysfunctions in Cytotoxicity, Pro-inflammation, Permeability, and Apoptosis Induced by ROS Generation.

PubMed

Tseng, Chia-Yi; Wang, Jhih-Syuan; Chao, Ming-Wei

2017-10-01

Epidemiological studies suggest that an increase of diesel exhaust particles (DEP) in ambient air corresponds to an increase in hospital-recorded myocardial infarctions within 48 h after exposure. Among the many theories to explain this data are endothelial dysfunction and translocation of DEP into vasculature. The mechanisms for such DEP-induced vascular permeability remain unknown. One of the major mechanisms underlying the effects of DEP is suggested to be oxidative stress. Experiments have shown that DEP induce the generation of reactive oxygen species (ROS), such as superoxide anion and H 2 O 2 in the HUVEC tube cells. Transcription factor Nrf2 is translocated to the cell nucleus, where it activates transcription of the antioxidative enzyme HO-1 and sequentially induces the release of vascular permeability factor VEGF-A. Furthermore, a recent study shows that DEP-induced intracellular ROS may cause the release of pro-inflammatory TNF-α and IL-6, which may induce endothelial permeability as well by promoting VEGF-A secretion independently of HO-1 activation. These results demonstrated that the adherens junction molecule, VE-cadherin, becomes redistributed from the membrane at cell-cell borders to the cytoplasm in response to DEP, separating the plasma membranes of adjacent cells. DEP were occasionally found in endothelial cell cytoplasm and in tube lumen. In addition, the induced ROS is cytotoxic to the endothelial tube-like HUVEC. Acute DEP exposure stimulates ATP depletion, followed by depolarization of their actin cytoskeleton, which sequentially inhibits PI3K/Akt activity and induces endothelial apoptosis. Nevertheless, high-dose DEP augments tube cell apoptosis up to 70 % but disrupts the p53 negative regulator Mdm2. In summary, exposure to DEP affects parameters influencing vasculature permeability and viability, i.e., oxidative stress and its upregulated antioxidative and pro-inflammatory responses, which sequentially induce vascular permeability factor, VEGF-A release and disrupt cell-cell junction integrity. While exposure to a low dose of DEP actin triggers cytoskeleton depolarization, reduces PI3K/Akt activity, and induces a p53/Mdm2 feedback loop, a high dose causes apoptosis by depleting Mdm2. Addition of ROS scavenger N-acetyl cysteine suppresses DEP-induced oxidative stress efficiently and reduces subsequent damages by increasing endogenous glutathione.

Effects of viscosity on endothelial cell damage under acoustic droplet vaporization

NASA Astrophysics Data System (ADS)

Seda, Robinson; Singh, Rahul; Li, David; Pitre, John; Putnam, Andrew; Fowlkes, J. Brian; Bull, Joseph

2014-11-01

Acoustic droplet vaporization (ADV) is a process by which stabilized superheated microdroplets are able to undergo phase transition with the aid of focused ultrasound. Gas bubbles resulting from ADV can provide local occlusion of the blood vessels supplying diseased tissue, such as tumors. The ADV process can also induce bioeffects that increase vessel permeability, which is beneficial for localized drug delivery. Previous in vitro studies have demonstrated that vaporization at the endothelial layer will affect cell attachment and viability. Several hypotheses have been proposed to elucidate the mechanism of damage including the generation of normal and shear stresses during bubble expansion. A single 3.5 MHz ultrasound pulse consisting of 8 cycles (~2.3 μs) and a 6 MPa peak rarefactional pressure was used to induce ADV on endothelial cells in media of different viscosities. Carboxylmethyl cellulose was added to the cell media to increase the viscosity up to 300 cP to and aid in the reduction of stresses during bubble expansion. The likelihood of cell damage was decreased when compared to our control (~1 cP), but it was still present in some cases indicating that the mechanism of damage does not depend entirely on viscous stresses associated with bubble expansion. This work was supported by NIH Grant R01EB006476.

Pore network properties of sandstones in a fault damage zone

NASA Astrophysics Data System (ADS)

Bossennec, Claire; Géraud, Yves; Moretti, Isabelle; Mattioni, Luca; Stemmelen, Didier

2018-05-01

The understanding of fluid flow in faulted sandstones is based on a wide range of techniques. These depend on the multi-method determination of petrological and structural features, porous network properties and both spatial and temporal variations and interactions of these features. The question of the multi-parameter analysis on fluid flow controlling properties is addressed for an outcrop damage zone in the hanging wall of a normal fault zone on the western border of the Upper Rhine Graben, affecting the Buntsandstein Group (Early Triassic). Diagenetic processes may alter the original pore type and geometry in fractured and faulted sandstones. Therefore, these may control the ultimate porosity and permeability of the damage zone. The classical model of evolution of hydraulic properties with distance from the major fault core is nuanced here. The hydraulic behavior of the rock media is better described by a pluri-scale model including: 1) The grain scale, where the hydraulic properties are controlled by sedimentary features, the distance from the fracture, and the impact of diagenetic processes. These result in the ultimate porous network characteristics observed. 2) A larger scale, where the structural position and characteristics (density, connectivity) of the fracture corridors are strongly correlated with both geo-mechanical and hydraulic properties within the damage zone.

The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome

PubMed Central

Spiropoulou, Christina F; Srikiatkhachorn, Anon

2013-01-01

The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity. PMID:23841977

The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome.

PubMed

Spiropoulou, Christina F; Srikiatkhachorn, Anon

2013-08-15

The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity.

Fracking, fracture, and permeability

NASA Astrophysics Data System (ADS)

Turcotte, D. L.; Norris, J.; Rundle, J. B.

2013-12-01

Injections of large volumes of water into tight shale reservoirs allows the extraction of oil and gas not previously accessible. This large volume 'super' fracking induces damage that allows the oil and/or gas to flow to an extraction well. The purpose of this paper is to provide a model for understanding super fracking. We assume that water is injected from a small spherical cavity into a homogeneous elastic medium. The high pressure of the injected water generates hoop stresses that reactivate natural fractures in the tight shales. These fractures migrate outward as water is added creating a spherical shell of damaged rock. The porosity associated with these fractures is equal to the water volume injected. We obtain an analytic expression for this volume. We apply our model to a typical tight shale reservoir and show that the predicted water volumes are in good agreement with the volumes used in super fracking.

Metal-nanotube composites as radiation resistant materials

NASA Astrophysics Data System (ADS)

González, Rafael I.; Valencia, Felipe; Mella, José; van Duin, Adri C. T.; So, Kang Pyo; Li, Ju; Kiwi, Miguel; Bringa, Eduardo M.

2016-07-01

The improvement of radiation resistance in nanocomposite materials is investigated by means of classical reactive molecular dynamics simulations. In particular, we study the influence of carbon nanotubes (CNTs) in an Ni matrix on the trapping and possible outgassing of He. When CNTs are defect-free, He atoms diffuse alongside CNT walls and, although there is He accumulation at the metal-CNT interface, no He trespassing of the CNT wall is observed, which is consistent with the lack of permeability of a perfect graphene sheet. However, when vacancies are introduced to mimic radiation-induced defects, He atoms penetrate CNTs, which play the role of nano-chimneys, allowing He atoms to escape the damaged zone and reduce bubble formation in the matrix. Consequently, composites made of CNTs inside metals are likely to display improved radiation resistance, particularly when radiation damage is related to swelling and He-induced embrittlement.

Contribution of neutrophils to acute lung injury.

PubMed

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Experimental tests of truncated diffusion in fault damage zones

NASA Astrophysics Data System (ADS)

Suzuki, Anna; Hashida, Toshiyuki; Li, Kewen; Horne, Roland N.

2016-11-01

Fault zones affect the flow paths of fluids in groundwater aquifers and geological reservoirs. Fault-related fracture damage decreases to background levels with increasing distance from the fault core according to a power law. This study investigated mass transport in such a fault-related structure using nonlocal models. A column flow experiment is conducted to create a permeability distribution that varies with distance from a main conduit. The experimental tracer response curve is preasymptotic and implies subdiffusive transport, which is slower than the normal Fickian diffusion. If the surrounding area is a finite domain, an upper truncated behavior in tracer response (i.e., exponential decline at late times) is observed. The tempered anomalous diffusion (TAD) model captures the transition from subdiffusive to Fickian transport, which is characterized by a smooth transition from power-law to an exponential decline in the late-time breakthrough curves.

Intrathecal infusion of a Ca(2+)-permeable AMPA channel blocker slows loss of both motor neurons and of the astrocyte glutamate transporter, GLT-1 in a mutant SOD1 rat model of ALS.

PubMed

Yin, Hong Z; Tang, Darryl T; Weiss, John H

2007-10-01

Elevated extracellular glutamate, resulting from a loss of astrocytic glutamate transport capacity, may contribute to excitotoxic motor neuron (MN) damage in ALS. Accounting for their high excitotoxic vulnerability, MNs possess large numbers of unusual Ca(2+)-permeable AMPA channels (Ca-AMPA channels), the activation of which triggers mitochondrial Ca(2+) overload and strong reactive oxygen species (ROS) generation. However, the causes of the astrocytic glutamate transport loss remain unexplained. To assess the role of Ca-AMPA channels on the evolution of pathology in vivo, we have examined effects of prolonged intrathecal infusion of the Ca-AMPA channel blocker, 1-naphthyl acetylspermine (NAS), in G93A transgenic rat models of ALS. In wild-type animals, immunoreactivity for the astrocytic glutamate transporter, GLT-1, was particularly strong around ventral horn MNs. However, a marked loss of ventral horn GLT-1 was observed, along with substantial MN damage, prior to onset of symptoms (90-100 days) in the G93A rats. Conversely, labeling with the oxidative marker, nitrotyrosine, was increased in the neuropil surrounding MNs in the transgenic animals. Compared to sham-treated G93A animals, 30-day NAS infusions (starting at 67+/-2 days of age) markedly diminished the loss of both MNs and of astrocytic GLT-1 labeling. These observations are compatible with the hypothesis that activation of Ca-AMPA channels on MNs contributes, likely in part through oxidative mechanisms, to loss of glutamate transporter in surrounding astrocytes.

X-ray imaging of water motion during capillary imbibition: A study on how compaction bands impact fluid flow in Bentheim sandstone

NASA Astrophysics Data System (ADS)

Pons, A.; David, C.; Fortin, J.; Stanchits, S.; MenéNdez, B.; Mengus, J. M.

2011-03-01

To investigate the effect of compaction bands (CB) on fluid flow, capillary imbibition experiments were performed on Bentheim sandstone specimens (initial porosity ˜22.7%) using an industrial X-ray scanner. We used a three-step procedure combining (1) X-ray imaging of capillary rise in intact Bentheim sandstone, (2) formation of compaction band under triaxial tests, at 185 MPa effective pressure, with acoustic emissions (AE) recording for localization of the induced damage, and (3) again X-ray imaging of capillary rise in the damaged specimens after the unloading. The experiments were performed on intact cylindrical specimens, 5 cm in diameter and 10.5 cm in length, cored in different orientations (parallel or perpendicular to the bedding). Analysis of the images obtained at different stages of the capillary imbibition shows that the presence of CB slows down the imbibition and disturbs the geometry of water flow. In addition, we show that the CB geometry derived from X-ray density maps analysis is well correlated with the AE location obtained during triaxial test. The analysis of the water front kinetics was conducted using a simple theoretical model, which allowed us to confirm that compaction bands act as a barrier for fluid flow, not fully impermeable though. We estimate a contrast of permeability of a factor of ˜3 between the host rock and the compaction bands. This estimation of the permeability inside the compaction band is consistent with estimations done in similar sandstones from field studies but differs by 1 order of magnitude from estimations from previous laboratory measurements.

Identification and characterization of cannabinoids that induce cell death through mitochondrial permeability transition in Cannabis leaf cells.

PubMed

Morimoto, Satoshi; Tanaka, Yumi; Sasaki, Kaori; Tanaka, Hiroyuki; Fukamizu, Tomohide; Shoyama, Yoshinari; Shoyama, Yukihiro; Taura, Futoshi

2007-07-13

Cannabinoids are secondary metabolites stored in capitate-sessile glands on leaves of Cannabis sativa. We discovered that cell death is induced in the leaf tissues exposed to cannabinoid resin secreted from the glands, and identified cannabichromenic acid (CBCA) and Delta(1)-tetrahydrocannabinolic acid (THCA) as unique cell death mediators from the resin. These cannabinoids effectively induced cell death in the leaf cells or suspension-cultured cells of C. sativa, whereas pretreatment with the mitochondrial permeability transition (MPT) inhibitor cyclosporin A suppressed this cell death response. Examinations using isolated mitochondria demonstrated that CBCA and THCA mediate opening of MPT pores without requiring Ca(2+) and other cytosolic factors, resulting in high amplitude mitochondrial swelling, release of mitochondrial proteins (cytochrome c and nuclease), and irreversible loss of mitochondrial membrane potential. Therefore, CBCA and THCA are considered to cause serious damage to mitochondria through MPT. The mitochondrial damage was also confirmed by a marked decrease of ATP level in cannabinoid-treated suspension cells. These features are in good accord with those of necrotic cell death, whereas DNA degradation was also observed in cannabinoid-mediated cell death. However, the DNA degradation was catalyzed by nuclease(s) released from mitochondria during MPT, indicating that this reaction was not induced via a caspase-dependent apoptotic pathway. Furthermore, the inhibition of the DNA degradation only slightly blocked the cell death induced by cannabinoids. Based on these results, we conclude that CBCA and THCA have the ability to induce necrotic cell death via mitochondrial dysfunction in the leaf cells of C. sativa.

Atorvastatin prevents angiotensin II-induced high permeability of human arterial endothelial cell monolayers via ROCK signaling pathway.

PubMed

Yi, Ren; Xiao-Ping, Gao; Hui, Liang

2015-03-27

Intracranial aneurysm, as a common cause of cerebral hemorrhage, is often discovered when the aneurysm ruptures, causing subarachnoid hemorrhage. Unfortunately, the formation of cerebral aneurysm, which is associated with endothelial damage and macrophage migration, still cannot be prevented now. Tight junctions (TJs) open due to the disappearance of TJ proteins occludin and zona occludens-1 (ZO-1) in damaged endothelia, thus allowing macrophage migration and forming cerebral aneurysm. Therefore, cerebral aneurysm formation can be prevented by increasing TJs of the artery endothelium. Interestingly, statin, which can reduce saccular aneurysm, may prevent aneurysm formation through acting on different steps, but the underlying mechanism remains unclear. In this study, angiotensin II (Ang II) significantly increased the permeability of human arterial endothelial cell (HAEC). Moreover, the distribution of ZO-1 in cell-cell junction area and the total expression in HAECs were significantly decreased by Ang II treatment. However, the abnormal distribution and decreased expression of ZO-1 and hyperpermeability of HAECs were significantly reversed by pretreatment with atorvastatin. Furthermore, Ang II-induced phosphorylations of MYPT1, LIMK and MLC2 were significantly inhibited with atorvastatin or Rho kinase (ROCK) inhibitor (H1152) pretreatment. Knockdown of ROCK-II probably abolished Ang II-induced abnormal ZO-1 distribution and expression deficiency and hyperpermeability of HAECs. In conclusion, atorvastatin prevented Ang II-induced rupture of HAEC monolayers by suppressing the ROCK signaling pathway. Our results may explain, at least in part, some beneficial effects of statins on cardiovascular diseases such as intracranial aneurysm. Copyright © 2015 Elsevier Inc. All rights reserved.

Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.

PubMed

Garas, Lydia C; Feltrin, Cristiano; Hamilton, M Kristina; Hagey, Jill V; Murray, James D; Bertolini, Luciana R; Bertolini, Marcelo; Raybould, Helen E; Maga, Elizabeth A

2016-02-01

Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.

Investigation of functional and morphological changes in Pseudomonas aeruginosa and Staphylococcus aureus cells induced by Origanum compactum essential oil.

PubMed

Bouhdid, S; Abrini, J; Zhiri, A; Espuny, M J; Manresa, A

2009-05-01

Evaluation of the cellular effects of Origanum compactum essential oil on Pseudomonas aeruginosa ATCC 27853 and Staphylococcus aureus ATCC 29213. The damage induced by O. compactum essential oil on these two strains has been studied using different techniques: plate count, potassium leakage, flow cytometry (FC) and transmission electron microscopy (TEM). The results showed that oil treatment led to reduction of cells viability and dissipated potassium ion gradients. Flow cytometric analysis showed that oil treatment promoted the accumulation of bis-oxonol and the membrane-impermeable nucleic acid stain propidium iodide (PI), indicating the loss of membrane potential and permeability. The ability to reduce 5-cyano-2,3-ditolyl tetrazolium chloride was inhibited. Unlike in Ps. aeruginosa, membrane potential and membrane permeability in Staph. aureus cells were affected by oil concentration and contact time. Finally, TEM showed various structural effects. Mesosome-like structures were seen in oil-treated Staph. aureus cells whereas in Ps. aeruginosa, coagulated cytoplasmic material and liberation of membrane vesicles were observed, and intracellular material was seen in the surrounding environment. Both FC and TEM revealed that the effects in Ps. aeruginosa were greater than in Staph. aureus. Oregano essential oil induces membrane damage showed by the leakage of potassium and uptake of PI and bis-oxonol. Ultrastructural alterations and the loss of cell viability were observed. Understanding the mode of antibacterial effect of the oil studied is of a great interest in it further application as natural preservative in food or pharmaceutical industries.

Effect of lycopene on the blood-spinal cord barrier after spinal cord injury in mice.

PubMed

Zhang, Qian; Wang, Jianbo; Gu, Zhengsong; Zhang, Qing; Zheng, Hong

2016-09-05

The current study aimed to investigate the effect of lycopene on the blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) in a mouse model. Lycopene inhibited lipid peroxidation and oxidative DNA damage as a highly efficient antioxidant and free radical scavenger. Lycopene (4 mg/kg/d) was administrated immediately following SCI. The permeability of the BSCB and water content in the spinal cord tissue were evaluated. Additionally, levels of expression of tight junction proteins and heme oxygenase-1 (HO-1) were determined with Western blotting. An enzyme-linked immunosorbent assay analysis of spinal cord tissue homogenates was performed 48 h after SCI to evaluate the expression of inflammation-related cytokines. In addition, recovery of motor function was assessed 1 d, 2 d, 5 d, 10 d, and 15 d after SCI using the Basso Mouse Scale to score locomotion. Compared to the group with an untreated SCI, mice with an SCI treated with lycopene had significantly reduced spinal cord tissue water content and BSCB permeability. Furthermore, motor function of mice with an SCI was also greatly improved by lycopene administration. The expression of the proinflammatory factors TNF-α and NF-kB increased markedly 48 h after SCI, and their upregulation was significantly attenuated by lycopene treatment. The expression of molecules that protect tight junctions, zonula occluden-1 and claudin-5, was upregulated by lycopene treatment after SCI. Taken together, these results clearly indicate that lycopene attenuated SCI by promoting repair of the damaged BSCB, so lycopene is a novel and promising treatment for SCI in humans.

On the mechanism of polypropylene fibres in preventing fire spalling in self-compacting and high-performance cement paste

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X.; Magnel Laboratory for Concrete Research, Department of Structural Engineering, Ghent University, Technologiepark-Zwijnaarde 904 B-9052, Ghent; Ye, G.

2008-04-15

With the increasing application of self-compacting concrete (SCC) in construction and infrastructure, the fire spalling behavior of SCC has been attracting due attention. In high performance concrete (HPC), addition of polypropylene fibers (PP fibers) is widely used as an effective method to prevent explosive spalling. Hence, it would be useful to investigate whether the PP fibers are also efficient in SCC to avoid explosive spalling. However, no universal agreement exists concerning the fundamental mechanism of reducing the spalling risk by adding PP fiber. For SCC, the reduction of flowability should be considered when adding a significant amount of fibres. Inmore » this investigation, both the micro-level and macro-level properties of pastes with different fiber contents were studied in order to investigate the role of PP fiber at elevated temperature in self-compacting cement paste samples. The micro properties were studied by backscattering electron microscopy (BSE) and mercury intrusion porosimetry (MIP) tests. The modification of the pore structure at elevated temperature was investigated as well as the morphology of the PP fibers. Some macro properties were measured, such as the gas permeability of self-compacting cement paste after heating at different temperatures. The factors influencing gas permeability were analyzed. It is shown that with the melting of PP fiber, no significant increase in total pore volume is obtained. However, the connectivity of isolated pores increases, leading to an increase of gas permeability. With the increase of temperature, the addition of PP fibers reduces the damage of cement pastes, as seen from the total pore volume and the threshold pore diameter changes. From this investigation, it is concluded that the connectivity of pores as well as the creation of micro cracks are the major factors which determine the gas permeability after exposure to high temperatures. Furthermore, the connectivity of the pores acts as a dominant factor for temperatures below 300 deg. C. For higher temperatures micro cracks are becoming the major factor which influences the gas permeability.« less

Hydraulic Shearing and Hydraulic Jacking Observed during Hydraulic Stimulations in Fractured Geothermal Reservoir in Pohang, Korea

NASA Astrophysics Data System (ADS)

Min, K. B.; Park, S.; Xie, L.; Kim, K. I.; Yoo, H.; Kim, K. Y.; Choi, J.; Yoon, K. S.; Yoon, W. S.; Lee, T. J.; Song, Y.

2017-12-01

Enhanced Geothermal System (EGS) relies on sufficient and irreversible enhancement of reservoir permeability through hydraulic stimulation and possibility of such desirable change of permeability is an open question that can undermine the universality of EGS concept. We report results of first hydraulic stimulation campaign conducted in two deep boreholes in fractured granodiorite geothermal reservoir in Pohang, Korea. Borehole PX-1, located at 4.22 km, was subjected to the injection of 3,907 m3 with flow rate of up to 18 kg/s followed by bleeding off of 1,207 m3. The borehole PX-2, located at 4.35 km, was subjected to the injection of 1,970 m3 with flow rate of up to 46 kg/sIn PX-1, a sharp distinct decline of wellhead pressure was observed at around 16 MPa of wellhead pressure which was similar to the predicted injection pressure to induce hydraulic shearing. Injectivity interpretation before and after the hydraulic shearing indicates that permanent increase of permeability was achieved by a factor of a few. In PX-2, however, injectivity was very small and hydraulic shearing was not observed due possibly to the near wellbore damage made by the remedying process of lost circulation such as using lost circulation material during drilling. Flow rate of larger than 40 kg/s was achieved at very high well head pressure of nearly 90 MPa. Hydraulic jacking, that is reversible opening and closure of fracture with change of injection pressure, was clearly observed. Although sharp increase of permeability due to fracture opening was achieved with elevated injection pressure, the increased permeability was reversed with decreased injection pressure.Two contrasting response observed in the same reservoir at two different boreholes which is apart only 600 m apart provide important implication that can be used for the stimulation strategy for EGS.This work was supported by the New and Renewable Energy Technology Development Program of the Korea Institute of Energy Technology Evaluation and Planning (KETEP) through a grant funded by the Korean Government's Ministry of Trade, Industry & Energy (No. 20123010110010).

Interaction between Proppant Packing, Reservoir Depletion, and Fluid Flow in Pore Space

NASA Astrophysics Data System (ADS)

Fan, M.; McClure, J. E.; Han, Y.; Chen, C.

2016-12-01

In the oil and gas industry, the performance of proppant pack in hydraulically created fractures has a significant influence on fracture conductivity. A better understanding of proppant transport and deposition pattern in a hydraulic fracture is vital for effective and economical production within oil and gas reservoirs. In this research, a numerical modeling approach, combining Particle Flow Code (PFC) and GPU-enhanced lattice Boltzmann simulator (GELBS), is adopted to advance the understanding of the interaction between proppant particle packing, depletion of reservoir formation, and transport of reservoir flow through the pore space. In this numerical work flow, PFC is used to simulate effective stress increase and proppant particle movement and rearrangement under increasing mechanical loading. The pore structure of the proppant pack evolves subsequently and the geometrical data are output for lattice Boltzmann (LB) simulation of proppant pack permeability. Three different proppant packs with fixed particle concentration and 12/18, 16/30, and 20/40 mesh sizes are generated. These proppant packs are compressed with specified loading stress and their subsequent geometries are used for fluid flow simulations. The simulation results are in good agreement with experimental observations, e.g., the conductivity of proppant packs decreases with increasing effective stress. Three proppant packs with the same average diameter were generated using different coefficients of variation (COVs) for the proppant diameter (namely cov5%, cov20%, and cov30%). By using the coupled PFC-LBM work flow, the proppant pack permeability as functions of effective stress and porosity is investigated. The results show that the proppant pack with a higher proppant diameter COV has lower permeability and porosity under the same effective stress, because smaller particles fill in the pore space between bigger particles. The relationship between porosity and permeability is also consistent with the Kozeny-Carman equation. In addition, relative permeability curves are obtained using multiphase LB simulation to study non-wetting phase trapping, which will benefit production forecasting and interpretation of formation damage. This research provides an advantageous alternative to expensive laboratory experiments.

Effectiveness of cuticular transpiration barriers in a desert plant at controlling water loss at high temperatures.

PubMed

Schuster, Ann-Christin; Burghardt, Markus; Alfarhan, Ahmed; Bueno, Amauri; Hedrich, Rainer; Leide, Jana; Thomas, Jacob; Riederer, Markus

2016-01-01

Maintaining the integrity of the cuticular transpiration barrier even at elevated temperatures is of vital importance especially for hot-desert plants. Currently, the temperature dependence of the leaf cuticular water permeability and its relationship with the chemistry of the cuticles are not known for a single desert plant. This study investigates whether (i) the cuticular permeability of a desert plant is lower than that of species from non-desert habitats, (ii) the temperature-dependent increase of permeability is less pronounced than in those species and (iii) whether the susceptibility of the cuticular permeability barrier to high temperatures is related to the amounts or properties of the cutin or the cuticular waxes. We test these questions with Rhazya stricta using the minimum leaf water vapour conductance (gmin) as a proxy for cuticular water permeability. gmin of R. stricta (5.41 × 10(-5) m s(-1) at 25 °C) is in the upper range of all existing data for woody species from various non-desert habitats. At the same time, in R. stricta, the effect of temperature (15-50 °C) on gmin (2.4-fold) is lower than in all other species (up to 12-fold). Rhazya stricta is also special since the temperature dependence of gmin does not become steeper above a certain transition temperature. For identifying the chemical and physical foundation of this phenomenon, the amounts and the compositions of cuticular waxes and cutin were determined. The leaf cuticular wax (251.4 μg cm(-2)) is mainly composed of pentacyclic triterpenoids (85.2% of total wax) while long-chain aliphatics contribute only 3.4%. In comparison with many other species, the triterpenoid-to-cutin ratio of R. stricta (0.63) is high. We propose that the triterpenoids deposited within the cutin matrix restrict the thermal expansion of the polymer and, thus, prevent thermal damage to the highly ordered aliphatic wax barrier even at high temperatures. Published by Oxford University Press on behalf of the Annals of Botany Company.

Deferoxamine inhibits microglial activation, attenuates blood-brain barrier disruption, rescues dendritic damage, and improves spatial memory in a mouse model of microhemorrhages.

PubMed

He, Xiao-Fei; Lan, Yue; Zhang, Qun; Liu, Dong-Xu; Wang, Qinmei; Liang, Feng-Ying; Zeng, Jin-Sheng; Xu, Guang-Qing; Pei, Zhong

2016-08-01

Cerebral microbleeds are strongly linked to cognitive dysfunction in the elderly. Iron accumulation plays an important role in the pathogenesis of intracranial hemorrhage. Deferoxamine (DFX), a metal chelator, removes iron overload and protects against brain damage in intracranial hemorrhage. In this study, the protective effects of DFX against microhemorrhage were examined in mice. C57BL6 and Thy-1 green fluorescent protein transgenic mice were subjected to perforating artery microhemorrhages on the right posterior parietal cortex using two-photon laser irradiation. DFX (100 mg/kg) was administered 6 h after microhemorrhage induction, followed by every 12 h for three consecutive days. The water maze task was conducted 7 days after induction of microhemorrhages, followed by measurement of blood-brain barrier permeability, iron deposition, microglial activation, and dendritic damage. Laser-induced multiple microbleeds in the right parietal cortex clearly led to spatial memory disruption, iron deposits, microglial activation, and dendritic damage, which were significantly attenuated by DFX, supporting the targeting of iron overload as a therapeutic option and the significant potential of DFX in microhemorrhage treatment. Irons accumulation after intracranial hemorrhage induced a serious secondary damage to the brain. We proposed that irons accumulation after parietal microhemorrhages impaired spatial cognition. After parietal multiple microhemorrhages, increased irons and ferritin contents induced blood-brain barrier disruption, microglial activation, and further induced dendrites loss, eventually impaired the water maze, deferoxamine treatment protected from these damages. © 2016 International Society for Neurochemistry.

Electrolyte leakage and lipid degradation account for cold sensitivity in leaves of Coffea sp. plants.

PubMed

Campos, Paula Scotti; Quartin, Virgínia; Ramalho, José Cochicho; Nunes, Maria Antonieta

2003-03-01

Five Coffea genotypes differing in their sensitivity to low positive temperatures were compared with regard to the effects of chilling on membrane integrity, as well as their ability to recover from cold-induced injury upon re-warming. Membrane damage was evaluated through electrolyte leakage, changes in membrane lipid composition and malondialdehyde (MDA) production in control conditions (25/20 degrees C, day/night), after a gradual temperature decrease period to 15/10 degrees C, after chilling treatment (3 nights at 4 degrees C) and upon re-warming to 25/20 degrees C during 6 days (recovery). C. dewevrei showed the highest electrolyte leakage at 15/10 degrees C and after chilling. This was due mainly to lipid degradation observed at 15/10 degrees C, reflecting strong membrane damage. Furthermore, MDA production after chilling conditions indicated the occurrence of lipid peroxidation. A higher susceptibility of C. dewevrei to cold also was inferred from the complete absence of recovery as regards permeability, contrary to what was observed in the remaining plants. Apoatã and Piatã presented significant leakage values after chilling. However, such effects were reversible under recovery conditions. Exposure to cold (15/10 degrees C and 3 x 15/4 degrees C) did not significantly affect membrane permeability in Catuaí and Icatú. Furthermore, no significant MDA production was observed even after chilling treatments in Apoatã, Piatã, Catuaí and Icatú, suggesting that the four genotypes had the ability to maintain membrane integrity and/or repair membrane damage caused by low temperatures. Apoatã, Piatã and, to a lower extent, Catuaí, were able to cope with gradual temperature decrease through an enhanced lipid biosynthesis. After acclimation, Piatã and Catuaí showed a lowering of digalactosyldiacylglycerol to monogalactosyldiacylglycerol ratio (MGDG/DGDG) as a result of enhanced DGDG synthesis, which represents an increase in membrane stability. The same was observed in Apoatã after chilling, in spite of phospholipids decrease. The studied parameters clearly indicated that chilling induced irreversible membrane damage in C. dewevrei. We also concluded that increased lipid synthesis, lower MGDG/DGDG ratio, and changes in membrane unsaturation occurring during acclimation to low temperatures may be critical factors in maintenance of cellular integrity under chilling.

Investigation of mud density and weighting materials effect on drilling fluid filter cake properties and formation damage

NASA Astrophysics Data System (ADS)

Fattah, K. A.; Lashin, A.

2016-05-01

Drilling fluid density/type is an important factor in drilling and production operations. Most of encountered problems during rotary drilling are related to drilling mud types and weights. This paper aims to investigate the effect of mud weight on filter cake properties and formation damage through two experimental approaches. In the first approach, seven water-based drilling fluid samples with same composition are prepared with different densities (9.0-12.0 lb/gal) and examined to select the optimum mud weight that has less damage. The second approach deals with investigating the possible effect of the different weighting materials (BaSO4 and CaCO3) on filter cake properties. High pressure/high temperature loss tests and Scanning Electron Microscopy (SEM) analyses were carried out on the filter cake (two selected samples). Data analysis has revealed that mud weigh of 9.5 lb/gal has the less reduction in permeability of ceramic disk, among the seven used mud densities. Above 10.5 ppg the effect of the mud weight density on formation damage is stabilized at constant value. Fluids of CaCO3-based weighting material, has less reduction in the porosity (9.14%) and permeability (25%) of the filter disk properties than the BaSO4-based fluid. The produced filter cake porosity increases (from 0.735 to 0.859) with decreasing of fluid density in case of drilling samples of different densities. The filtration loss tests indicated that CaCO3 filter cake porosity (0.52) is less than that of the BaSO4 weighted material (0.814). The thickness of the filter cake of the BaSO4-based fluid is large and can cause some problems. The SEM analysis shows that some major elements do occur on the tested samples (Ca, Al, Si, and Ba), with dominance of Ca on the expense of Ba for the CaCO3 fluid sample and vice versa. The less effect of 9.5 lb/gal mud sample is reflected in the well-produced inter-particle pore structure and relatively crystal size. A general recommendation is given to minimize the future utilization of Barium Sulfate as a drilling fluid.

Simulation of Anisotropic Rock Damage for Geologic Fracturing

NASA Astrophysics Data System (ADS)

Busetti, S.; Xu, H.; Arson, C. F.

2014-12-01

A continuum damage model for differential stress-induced anisotropic crack formation and stiffness degradation is used to study geologic fracturing in rocks. The finite element-based model solves for deformation in the quasi-linear elastic domain and determines the six component damage tensor at each deformation increment. The model permits an isotropic or anisotropic intact or pre-damaged reference state, and the elasticity tensor evolves depending on the stress path. The damage variable, similar to Oda's fabric tensor, grows when the surface energy dissipated by three-dimensional opened cracks exceeds a threshold defined at the appropriate scale of the representative elementary volume (REV). At the laboratory or wellbore scale (<1m) brittle continuum damage reflects microcracking, grain boundary separation, grain crushing, or fine delamination, such as in shale. At outcrop (1m-100m), seismic (10m-1000m), and tectonic (>1000m) scales the damaged REV reflects early natural fracturing (background or tectonic fracturing) or shear strain localization (fault process zone, fault-tip damage, etc.). The numerical model was recently benchmarked against triaxial stress-strain data from laboratory rock mechanics tests. However, the utility of the model to predict geologic fabric such as natural fracturing in hydrocarbon reservoirs was not fully explored. To test the ability of the model to predict geological fracturing, finite element simulations (Abaqus) of common geologic scenarios with known fracture patterns (borehole pressurization, folding, faulting) are simulated and the modeled damage tensor is compared against physical fracture observations. Simulated damage anisotropy is similar to that derived using fractured rock-mass upscaling techniques for pre-determined fracture patterns. This suggests that if model parameters are constrained with local data (e.g., lab, wellbore, or reservoir domain), forward modeling could be used to predict mechanical fabric at the relevant REV scale. This reference fabric also can be used as the starting material property to pre-condition subsequent deformation or fluid flow. Continuing efforts are to expand the present damage model to couple damage evolution with plasticity and with permeability for more geologically realistic simulation.

Nitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrier

PubMed Central

Olivera, Gabriela C.; Ren, Xiaoyuan; Vodnala, Suman K.; Lu, Jun; Coppo, Lucia; Leepiyasakulchai, Chaniya; Holmgren, Arne; Kristensson, Krister; Rottenberg, Martin E.

2016-01-01

Nitric oxide (NO) generated by inducible NO synthase (iNOS) is critical for defense against intracellular pathogens but may mediate inflammatory tissue damage. To elucidate the role of iNOS in neuroinflammation, infections with encephalitogenic Trypanosoma brucei parasites were compared in inos -/- and wild-type mice. Inos -/- mice showed enhanced brain invasion by parasites and T cells, and elevated protein permeability of cerebral vessels, but similar parasitemia levels. Trypanosome infection stimulated T cell- and TNF-mediated iNOS expression in perivascular macrophages. NO nitrosylated and inactivated pro-inflammatory molecules such as NF-κΒp65, and reduced TNF expression and signalling. iNOS-derived NO hampered both TNF- and T cell-mediated parasite brain invasion. In inos -/- mice, TNF stimulated MMP, including MMP9 activity that increased cerebral vessel permeability. Thus, iNOS-generated NO by perivascular macrophages, strategically located at sites of leukocyte brain penetration, can serve as a negative feed-back regulator that prevents unlimited influx of inflammatory cells by restoring the integrity of the blood-brain barrier. PMID:26915097

Application of Layered Perforation Profile Control Technique to Low Permeable Reservoir

NASA Astrophysics Data System (ADS)

Wei, Sun

2018-01-01

it is difficult to satisfy the demand of profile control of complex well section and multi-layer reservoir by adopting the conventional profile control technology, therefore, a research is conducted on adjusting the injection production profile with layered perforating parameters optimization. i.e. in the case of coproduction for multi-layer, water absorption of each layer is adjusted by adjusting the perforating parameters, thus to balance the injection production profile of the whole well section, and ultimately enhance the oil displacement efficiency of water flooding. By applying the relationship between oil-water phase percolation theory/perforating damage and capacity, a mathematic model of adjusting the injection production profile with layered perforating parameters optimization, besides, perforating parameters optimization software is programmed. Different types of optimization design work are carried out according to different geological conditions and construction purposes by using the perforating optimization design software; furthermore, an application test is done for low permeable reservoir, and the water injection profile tends to be balanced significantly after perforation with optimized parameters, thereby getting a good application effect on site.

Experimental Study on Cementitious Composites Embedded with Organic Microcapsules

PubMed Central

Wang, Xianfeng; Xing, Feng; Zhang, Ming; Han, Ningxu; Qian, Zhiwei

2013-01-01

The recovery behavior for strength and impermeability of cementitious composites embedded with organic microcapsules was investigated in this study. Mortar specimens were formed by mixing the organic microcapsules and a catalyst with cement and sand. The mechanical behaviors of flexural and compression strength were tested. The results showed that strength could increase by up to nine percent with the addition of a small amount of microcapsules and then decrease with an increasing amount of microcapsules. An orthogonal test for investigating the strength recovery rate was designed and implemented for bending and compression using the factors of water/cement ratio, amount of microcapsules, and preloading rate. It is shown that the amount of microcapsules plays a key role in the strength recovery rate. Chloride ion permeability tests were also carried out to investigate the recovery rate and healing effect. The initial damage was obtained by subjecting the specimens to compression. Both the recovery rate and the healing effect were nearly proportional to the amount of microcapsules. The obtained cementitious composites can be seen as self-healing owing to their recovery behavior for both strength and permeability. PMID:28788318

Melatonin and human mitochondrial diseases

PubMed Central

Sharafati-Chaleshtori, Reza; Shirzad, Hedayatollah; Rafieian-Kopaei, Mahmoud; Soltani, Amin

2017-01-01

Mitochondrial dysfunction is one of the main causative factors in a wide variety of complications such as neurodegenerative disorders, ischemia/reperfusion, aging process, and septic shock. Decrease in respiratory complex activity, increase in free radical production, increase in mitochondrial synthase activity, increase in nitric oxide production, and impair in electron transport system and/or mitochondrial permeability are considered as the main factors responsible for mitochondrial dysfunction. Melatonin, the pineal gland hormone, is selectively taken up by mitochondria and acts as a powerful antioxidant, regulating the mitochondrial bioenergetic function. Melatonin increases the permeability of membranes and is the stimulator of antioxidant enzymes including superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase. It also acts as an inhibitor of lipoxygenase. Melatonin can cause resistance to oxidation damage by fixing the microsomal membranes. Melatonin has been shown to retard aging and inhibit neurodegenerative disorders, ischemia/reperfusion, septic shock, diabetes, cancer, and other complications related to oxidative stress. The purpose of the current study, other than introducing melatonin, was to present the recent findings on clinical effects in diseases related to mitochondrial dysfunction including diabetes, cancer, gastrointestinal diseases, and diseases related to brain function. PMID:28400824

Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

PubMed

Costa, Rute A P; Fernandes, Mariana P; de Souza-Pinto, Nadja C; Vercesi, Aníbal E

2013-02-15

Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. Copyright © 2013 Elsevier B.V. All rights reserved.

Membrane of Candida albicans as a target of berberine.

PubMed

Zorić, Nataša; Kosalec, Ivan; Tomić, Siniša; Bobnjarić, Ivan; Jug, Mario; Vlainić, Toni; Vlainić, Josipa

2017-05-17

We investigated the mechanisms of anti-Candida action of isoquinoline alkaloid berberine, active constituent of medically important plants of Barberry species. The effects on membrane, morphological transition, synthesis of ergosterol and the consequent changes in membrane permeability have been studied. Polarization and lipid peroxidation level of the membrane following berberine treatment have been addressed. Minimal inhibitory concentration (MIC) of berberine against C. albicans was 17.75 μg/mL. Cytotoxic effect of berberine was concentration dependent, and in sub-MIC concentrations inhibit morphological transition of C. albicans cells to its filamentous form. Results showed that berberine affects synthesis of membrane ergosterol dose-dependently and induces increased membrane permeability causing loss of intracellular material to the outer space (DNA/protein leakage). Berberine also caused membrane depolarization and lipid peroxidation of membrane constituents indicating its direct effect on the membrane. Moreover, ROS levels were also increased following berberine treatment indicating further the possibility of membrane damage. Based on the obtained results it seems that berberine achieves its anti-Candida activity by affecting the cell membrane.

Permeability of latex gloves after contact with dental materials.

PubMed

Richards, J M; Sydiskis, R J; Davidson, W M; Josell, S D; Lavine, D S

1993-09-01

The use of latex examination gloves in the dental office has become the standard of care. However, the effectiveness of gloves as a barrier after coming into contact with specific dental materials is still uncertain. To examine the effects of dental materials is still uncertain. To examine the effects of dental materials on latex, 100 latex examination glove finger tips were divided into 10 groups. Each group was manipulated in a different dental material for 15 minutes. Permeability was detected by the passage of herpes virus across the latex membrane, rinsed from the inner glove surface and titrated onto Vero cells. Significant virus leakage was discovered in gloves treated with acrylic monomer, chloroform, and orange solvent. Little virus leakage was noted in bleach, soap, and 30% phosphoric acid etchant treated gloves, and no virus leakage was found with composite resin, ethanol, formocresol, and water treated gloves. These data were supported with scanning electron micrographs taken of the treated glove samples and comparing with the controls. When certain dental materials are manipulated while wearing gloves, irreversible damage to the material occurs and may increase the practitioner's exposure to pathogens.

Example of Qanats for the Sustainability of Groundwater Usage, Antalya-Turkey

NASA Astrophysics Data System (ADS)

Ciftci, Ismail; Leventeli, Yasemin

2017-12-01

The protection of the existing resources has become much more important than getting fresh water. The traditional methods, like well and pump, can reduce the groundwater level and dry up the reservoirs. On the other hand, there are some environmentally friendly methods like “qanat”. Qanat is a water management system which has been used to supply water in semi-arid and arid regions for a long time; for example, in Iran, Iraq, Morocco, Oman etc. The system consists of many vertical well connected by gently sloping tunnel with tapping into the groundwater table. The main idea is to reduce the evaporation and leakage, keep the natural balance of the groundwater without pumping. The main idea in this study is to find suitable places for qanats in terms of geology and hydrology and to create a model for new water projects in Antalya. A “pilot area” near to Elmalı, which is one of the districts of Antalya, is selected. The geological units in the area are permeable - highly permeable micritic limestone and impermeable - poor permeable claystone - siltstone. The surface waters in the area are generally seasonal. The physical and chemical properties of surface waters were determined. The water in the area was classified “as very good quality water for drinking” and “very good for irrigations”. Besides that, the study showed that “the geological model is very appropriate for “qanat” and to get water by gravitation without decreasing the groundwater table and damaging natural balance”.

Assessing deep-seated landslide susceptibility using 3-D groundwater and slope-stability analyses, southwestern Seattle, Washington

USGS Publications Warehouse

Brien, Dianne L.; Reid, Mark E.

2008-01-01

In Seattle, Washington, deep-seated landslides on bluffs along Puget Sound have historically caused extensive damage to land and structures. These large failures are controlled by three-dimensional (3-D) variations in strength and pore-water pressures. We assess the slope stability of part of southwestern Seattle using a 3-D limit-equilibrium analysis coupled with a 3-D groundwater flow model. Our analyses use a high-resolution digital elevation model (DEM) combined with assignment of strength and hydraulic properties based on geologic units. The hydrogeology of the Seattle area consists of a layer of permeable glacial outwash sand that overlies less permeable glacial lacustrine silty clay. Using a 3-D groundwater model, MODFLOW-2000, we simulate a water table above the less permeable units and calibrate the model to observed conditions. The simulated pore-pressure distribution is then used in a 3-D slope-stability analysis, SCOOPS, to quantify the stability of the coastal bluffs. For wet winter conditions, our analyses predict that the least stable areas are steep hillslopes above Puget Sound, where pore pressures are elevated in the outwash sand. Groundwater flow converges in coastal reentrants, resulting in elevated pore pressures and destabilization of slopes. Regions predicted to be least stable include the areas in or adjacent to three mapped historically active deep-seated landslides. The results of our 3-D analyses differ significantly from a slope map or results from one-dimensional (1-D) analyses.

Whole-brain radiation fails to boost intracerebral gefitinib concentration in patients with brain metastatic non-small cell lung cancer: a self-controlled, pilot study.

PubMed

Fang, Luo; Sun, Xiaojiang; Song, Yu; Zhang, Yiwen; Li, Fanzhu; Xu, Yaping; Ma, Shenglin; Lin, Nengming

2015-10-01

Whole-brain radiation therapy (WBRT) is generally considered as an efficient strategy to improve blood-brain barrier (BBB) permeability by damaging BBB structure and is therefore, used as a promising pretreatment of chemotherapy. However, the impact of radiotherapy on leaky BBB is still controversial for the reason that BBB of metastatic brain tumor lesion had been breached by tumor metastasizing. Herein, we conducted a self-controlled study to evaluate the effect of WBRT on the permeability of BBB in non-small cell lung cancer (NSCLC) patients with brain metastases (BM). A prospective self-controlled research was performed. Radiation-naive NSCLC patients with BM were enrolled and treated with gefitinib for 2 weeks, and then concurrently combined with WBRT for 2 weeks. Plasma and cerebrospinal fluid (CSF) before and after WBRT were collected on day 15 and 29 after the initiation of gefitinib treatment. The concentrations of gefitinib in these samples were measured by HPLC. Three patients were enrolled and evaluated. The concentrations of gefitinib in plasma and CSF pre-WBRT were comparable to those of post-WBRT. Consequently, no significant change was noted in the CSF-to-plasma ratios of gefitinib before and after WBRT (2.79 ± 1.47 vs. 2.35 ± 1.74 %, p = 0.123). The WBRT may not affect the BBB permeability by determining the concentration of gefitinib in NSCLC patients with BM.

Eicosapentaenoic Acid Enhances Heat Stress-Impaired Intestinal Epithelial Barrier Function in Caco-2 Cells

PubMed Central

Xiao, Guizhen; Tang, Liqun; Yuan, Fangfang; Zhu, Wei; Zhang, Shaoheng; Liu, Zhifeng; Geng, Yan; Qiu, Xiaowen

2013-01-01

Objective Dysfunction of the intestinal epithelial tight junction (TJ) barrier is known to have an important etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. Methods Human intestinal epithelial Caco-2 cells were pre-incubated with EPA, DHA or arachidonic acid (AA) and then exposed to heat stress. Transepithelial electrical resistance (TEER) and Horseradish Peroxidase (HRP) permeability were measured to analyze barrier integrity. Levels of TJ proteins, including occludin, ZO-1 and claudin-2, were analyzed by Western blot and localized by immunofluorescence microscopy. Messenger RNA levels were determined by quantitative real time polymerase chain reaction (Q-PCR). TJ morphology was observed by transmission electron microscopy. Results EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. EPA significantly elevated the expression of occludin and ZO-1, while DHA was less effective and AA was not at all effective. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pretreatment with EPA. Conclusion This study indicates for the first time that EPA is more potent than DHA in protecting against heat-induced permeability dysfunction and epithelial barrier damage of tight junction. PMID:24066055

Brain Damage from Soman-Induced Seizures Is Greatly Exacerbated by Dimethyl sulfoxide (DMSO): Modest Neuroprotection by 2-Aminoethyl diphenylborinate (2- APB), a Transient Receptor Potential Channel Inhibitor and Inositol 1,4,5-triphosphate Receptor Antagonist

DTIC Science & Technology

2008-03-04

whereby the depletion of calcium from intracellular stores (e.g., via IP3 or ryanodine receptor activation ) signals the opening of calcium permeable TRP...system and allowed at least 30 min to acclimate. Baseline ECoG activity and behavior were monitored for at least 15 min. Following baseline recordings...used because the former does not cross the blood-brain-barrier and will not diminish seizure activity or interfere with central effects of the

Purely numerical approach for analyzing flow to a well intercepting a vertical fracture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narasimhan, T.N.; Palen, W.A.

1979-03-01

A numerical method, based on an Integral Finite Difference approach, is presented to investigate wells intercepting fractures in general and vertical fractures in particular. Such features as finite conductivity, wellbore storage, damage, and fracture deformability and its influence as permeability are easily handled. The advantage of the numerical approach is that it is based on fewer assumptions than analytic solutions and hence has greater generality. Illustrative examples are given to validate the method against known solutions. New results are presenteed to demonstrate the applicability of the method to problems not apparently considered in the literature so far.

Essential role of TRPV2 ion channel in the sensitivity of dystrophic muscle to eccentric contractions.

PubMed

Zanou, Nadège; Iwata, Yuko; Schakman, Olivier; Lebacq, Jean; Wakabayashi, Shigeo; Gailly, Philippe

2009-11-19

Duchenne myopathy is a lethal disease due to the absence of dystrophin, a cytoskeletal protein. Muscles from dystrophin-deficient mice (mdx) typically present an exaggerated susceptibility to eccentric work characterized by an important force drop and an increased membrane permeability consecutive to repeated lengthening contractions. The present study shows that mdx muscles are largely protected from eccentric work-induced damage by overexpressing a dominant negative mutant of TRPV2 ion channel. This observation points out the role of TRPV2 channel in the physiopathology of Duchenne muscular dystrophy.

Characterizing flow pathways in a sandstone aquifer at multiple depths

NASA Astrophysics Data System (ADS)

Medici, Giacomo; West, Jared; Mountney, Nigel

2017-04-01

Sandstone aquifers are commonly assumed to represent porous media characterized by a permeable matrix. However, such aquifers may be heavily fractured where rock properties and timing of deformation favour brittle failure and crack opening. In many aquifer types, fractures associated with faults, bedding planes and stratabound joints represent preferential pathways for fluids and contaminants. This presentation reports well-test results and outcrop-scale studies that reveal how strongly lithified siliciclastic rocks may be entirely dominated by fracture flow at shallow depths (≤ 150 m), similar to limestone and crystalline aquifers. The Triassic St Bees Sandstone Formation of the UK East Irish Sea Basin represents an optimum succession for study of the influence of both sedimentary and tectonic aquifer heterogeneities in a strongly lithified sandstone aquifer-type. This sedimentary succession of fluvial origin accumulated in rapidly subsiding basins, which typically favour preservation of complete depositional cycles, including fine-grained mudstone and silty sandstone layers of floodplain origin interbedded with sandstone-dominated fluvial channel deposits. Vertical joints in the St Bees Sandstone Formation form a pervasive stratabound system whereby joints terminate at bedding-parallel discontinuities. Additionally, normal faults are present through the succession and record development of open-fractures in their damage zones. Here, the shallow aquifer (depth ≤150 m BGL) was characterized in outcrop and well tests. Fluid temperature, conductivity and flow-velocity logs record inflows and outflows from normal faults, as well as from pervasive bed-parallel fractures. Quantitative flow logging analyses in boreholes that cut fault planes indicate that zones of fault-related open fractures typically represent ˜ 50% of well transmissivity. The remaining flow component is dominated by bed-parallel fractures. However, such sub-horizontal fractures become the principal flow conduits in wells that penetrate the exterior parts of fault damage zones, as well as in non-faulted areas. Optical televiewer logs show development of karst-like conduits in correspondence of bedding fractures and faults up to 150 m below the ground surface, where recharge water containing dissolved carbonic acid enlarges fractures; these features may be responsible for the relatively high field-scale permeability (K˜0.1-1 m/day) of the phreatic zone at these depths. Below this 'karstifed' zone, field-scale permeability progressively decreases from K˜10-2 to 10-4 m/day from 150 m to 1100 m depth. Notably, differences between plug and field-scale permeability, and frequency of well in-flows seen in temperature and conductivity logs, also decrease between intermediate (150 to 450 m) and elevated (450 to 1100 m) depths. This confirms how fracture closure leads to a progressively more important matrix contribution to flow with increasing lithostatic stress, leading to intergranular flow dominance at ˜ 1 km depth.

Cumulative co-seismic fault damage and feedbacks on earthquake rupture

NASA Astrophysics Data System (ADS)

Mitchell, T. M.; Aben, F. M.; Ostermeijer, G.; Rockwell, T. K.; Doan, M. L.

2017-12-01

The importance of the damage zone in the faulting and earthquake process is widely recognized, but our understanding of how damage zones are created, what their properties are, and how they feed back into the seismic cycle, is remarkably poorly known. Firstly, damaged rocks have reduced elastic moduli, cohesion and yield strength, which can cause attenuation and potentially non-linear wave propagation effects during ruptures. Secondly, damaged fault rocks are generally more permeable than intact rocks, and hence play a key role in the migration of fluids in and around fault zones over the seismic cycle. Finally, the dynamic generation of damage as the earthquake propagates can itself influence the dynamics of rupture propagation, by increasing the amount of energy dissipation, decreasing the rupture velocity, modifying the size of the earthquake, changing the efficiency of weakening mechanisms such as thermal pressurisation of pore fluids, and even generating seismic waves itself . All of these effects imply that a feedback exists between the damage imparted immediately after rupture propagation, at the early stages of fault slip, and the effects of that damage on subsequent ruptures dynamics. In recent years, much debate has been sparked by the identification of so-called `pulverized rocks' described on various crustal-scale faults, a type of intensely damaged fault rock which has undergone minimal shear strain, and the occurrence of which has been linked to damage induced by transient high strain-rate stress perturbations during earthquake rupture. Damage induced by such transient stresses, whether compressional or tensional, likely constitute heterogeneous modulations of the remote stresses that will impart significant changes on the strength, elastic and fluid flow properties of a fault zone immediately after rupture propagation, at the early stage of fault slip. In this contribution, we will demonstrate laboratory and field examples of two dynamic mechanisms that have been proposed for the generation of pulverized rocks; (i) compressive loading by high-frequency stress pulses due to the radiation of seismic waves and (ii) explosive dilation in tension in rocks containing pressurized pore fluids.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Mechanism of oxidative DNA damage induction in a strict anaerobe, Prevotella melaninogenica.

PubMed

Takeuchi, T; Kato, N; Watanabe, K; Morimoto, K

2000-11-01

We investigated the mechanism of the oxidative DNA damage induction by exposure to O(2) in Prevotella melaninogenica, a strict anaerobe. Flow cytometry with hydroethidine and dichlorofluorescein diacetate showed that O(2) exposure generated O(2)*-) and H(2)O(2). Results of electron spin resonance with alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone and ethanol showed that O(2) exposure also induced *OH radical generation in P. melaninogenica loaded with FeCl(2) but not in samples without FeCl(2) loading. In P. melaninogenica, O(2) exposure increased 8-hydroxydeoxyguanosine (8OHdG), typical of oxidative DNA damage. Catalase inhibited the increase, but the *OH radical scavengers did not. Phenanthroline, a membrane-permeable Fe and Cu chelator, increased the 8OHdG induction. In FeCl(2)-loaded samples, induction of 8OHdG decreased. Addition of H(2)O(2) markedly increased 8OHdG levels. These results indicate that in P. melaninogenica, exposure to O(2) generated and accumulated O(2)* and H(2)O(2), and that a crypto-OH radical generated through H(2)O(2) was the active species in the 8OHdG induction.

The Effects of Aging on Pulmonary Oxidative Damage, Protein Nitration and Extracellular Superoxide Dismutase Down-Regulation During Systemic Inflammation

PubMed Central

Starr, Marlene E; Ueda, Junji; Yamamoto, Shoji; Evers, B. Mark; Saito, Hiroshi

2011-01-01

Systemic inflammatory response syndrome (SIRS), a serious clinical condition characterized by whole body inflammation, is particularly threatening for elderly patients who suffer much higher mortality rates than the young. A major pathological consequence of SIRS is acute lung injury caused by neutrophil-mediated oxidative damage. Previously, we reported an increase in protein tyrosine nitration (a marker of oxidative/nitrosative damage), and a decrease in antioxidant enzyme, extra-cellular superoxide dismutase (EC-SOD), in the lungs of young mice during endotoxemia-induced SIRS. Here we demonstrate that during endotoxemia, down-regulation of EC-SOD is significantly more profound and prolonged, while up-regulation of iNOS is augmented in aged compared to young mice. Aged mice also showed 2.5-fold higher protein nitration levels, compared to young mice, with particularly strong nitration in the pulmonary vascular endothelium during SIRS. Additionally, by 2-dimensional gel electrophoresis, Western blotting and mass spectrometry, we identified proteins which show increased tyrosine nitration in age- and SIRS-dependent manners; these proteins (profilin-1, transgelin-2, LASP 1, tropomyosin and myosin) include components of the actin cytoskeleton responsible for maintaining pulmonary vascular permeability. Reduced EC-SOD in combination with increased oxidative/nitrosative damage and altered cytoskeletal protein function due to tyrosine nitration may contribute to augmented lung injury in the aged with SIRS. PMID:21092756

HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: Potential role of the thiol antioxidant N-acetylcysteine amide

PubMed Central

Banerjee, Atrayee; Zhang, Xinsheng; Manda, Kalyan Reddy; Banks, William A; Ercal, Nuran

2010-01-01

An increased risk of HIV-1 associated dementia (HAD) has been observed in patients abusing methamphetamine (METH). Since both HIV viral proteins (gp120, Tat) and METH induce oxidative stress, drug abusing patients are at a greater risk of oxidative stress-induced damage. The objective of this study was to determine if N-acetylcysteine amide (NACA) protects the blood brain barrier (BBB) from oxidative stress-induced damage in animals exposed to gp120, Tat and METH. To study this, CD-1 mice pre-treated with NACA/saline, received injections of gp120, Tat, gp120 + Tat or saline for 5 days, followed by three injections of METH/saline on the fifth day, and sacrificed 24 h after the final injection. Various oxidative stress parameters were measured, and animals treated with gp120+Tat+Meth were found to be the most challenged group, as indicated by their GSH and MDA levels. Treatment with NACA significantly rescued the animals from oxidative stress. Further, NACA-treated animals had significantly higher expression of TJ proteins and BBB permeability as compared to the group treated with gp120+Tat+METH alone, indicating that NACA can protect the BBB from oxidative stress-induced damage in gp120, Tat and METH exposed animals, and thus could be a viable therapeutic option for patients with HAD. PMID:20188164

The hydraulic structure of the Gole Larghe Fault Zone (Italian Southern Alps) through the seismic cycle

NASA Astrophysics Data System (ADS)

Bistacchi, A.; Mittempergher, S.; Di Toro, G.; Smith, S. A. F.; Garofalo, P. S.

2017-12-01

The 600 m-thick, strike slip Gole Larghe Fault Zone (GLFZ) experienced several hundred seismic slip events at c. 8 km depth, well-documented by numerous pseudotachylytes, was then exhumed and is now exposed in beautiful and very continuous outcrops. The fault zone was also characterized by hydrous fluid flow during the seismic cycle, demonstrated by alteration halos and precipitation of hydrothermal minerals in veins and cataclasites. We have characterized the GLFZ with > 2 km of scanlines and semi-automatic mapping of faults and fractures on several photogrammetric 3D Digital Outcrop Models (3D DOMs). This allowed us obtaining 3D Discrete Fracture Network (DFN) models, based on robust probability density functions for parameters of fault and fracture sets, and simulating the fault zone hydraulic properties. In addition, the correlation between evidences of fluid flow and the fault/fracture network parameters have been studied with a geostatistical approach, allowing generating more realistic time-varying permeability models of the fault zone. Based on this dataset, we have developed a FEM hydraulic model of the GLFZ for a period of some tens of years, covering one seismic event and a postseismic period. The higher permeability is attained in the syn- to early post-seismic period, when fractures are (re)opened by off-fault deformation, then permeability decreases in the postseismic due to fracture sealing. The flow model yields a flow pattern consistent with the observed alteration/mineralization pattern and a marked channelling of fluid flow in the inner part of the fault zone, due to permeability anisotropy related to the spatial arrangement of different fracture sets. Amongst possible seismological applications of our study, we will discuss the possibility to evaluate the coseismic fracture intensity due to off-fault damage, and the heterogeneity and evolution of mechanical parameters due to fluid-rock interaction.

Protective effect of a Chinese Medicine formula He-Ying-Qing-Re Formula on diabetic retinopathy.

PubMed

Wang, Leilei; Wang, Ning; Tan, Hor-yue; Zhang, Yinjian; Feng, Yibin

2015-07-01

He-Ying-Qing-Re Formula (HF) is a formula modified from "Si-Miao-Yong-An Decoction", a traditional Chinese medical classic emerged in the Qing dynasty and has been reported for treatment of vascular diseases. HF, containing 8 herbs, has been used in local hospital for decades as a complementary method for diabetic retinopathy (DR) with retinal vascular dysfunction. Clinical reports revealed HF could ameliorate vision defects, microaneurysms, hemorrhages and macular edema. The aim of this study is to investigate the anti-DR action of HF and its underlying mechanism experimentally. Chromatographic fingerprinting of HF and rodent model of DR were established; hypoglycemic effect of HF was measured by fasting, random blood glucose and glucose tolerance test; vascular degeneration was measured by retinal digestion; blood-retina-barrier (BRB) permeability was assessed with Evans Blue leakage assay. Advanced glycation end products (AGEs) were measured in vitro and in vivo level; Migration of retinal vascular endothelial cells were determined by wound healing and transwell chamber assays; permeability of endothelial monolayer was monitored with dextran transport. AGEs-related proteins and signaling were measured with immunoblotting and immunohistochemistry. Chlorogenic acid, ferulic acid and arctin were identified as major components in HF; HF suppresses retinal vasculature degeneration and BRB permeability damage without significant inhibition on hyperglycemia; HF reduces in vitro and in vivo formation of AGEs and AGEs-induced migration as well as permeability of retinal vascular endothelial cells. Expression of tight junction proteins Zo-1 and Claudin-1 was increased while activation of AGEs receptor and downstream signaling Akt were suppressed upon HF treatment. HF exhibits protective effect against diabetic retinopathy, which may be associated with inhibition on AGEs and recovery on endothelial dysfunction via modulation of tight junction and AGEs downstream signaling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Adenovirus-delivered GFP-HO-1C[INCREMENT]23 attenuates blood-spinal cord barrier permeability after rat spinal cord contusion.

PubMed

Chang, Sheng; Bi, Yunlong; Meng, Xiangwei; Qu, Lin; Cao, Yang

2018-03-21

The blood-spinal cord barrier (BSCB) plays a key role in maintaining the microenvironment and is primarily composed of tight junction proteins and nonfenestrated capillary endothelial cells. After injury, BSCB damage results in increasing capillary permeability and release of inflammatory factors. Recent studies have reported that haem oxygenase-1 (HO-1) fragments lacking 23 amino acids at the C-terminus (HO-1C[INCREMENT]23) exert novel anti-inflammatory and antioxidative effects in vitro. However, no study has identified the role of HO-1C[INCREMENT]23 in vivo. We aimed to investigate the protective effects of HO-1C[INCREMENT]23 on the BSCB after spinal cord injury (SCI) in a rat model. Here, adenoviral HO-1C[INCREMENT]23 (Ad-GFP-HO-1C[INCREMENT]23) was intrathecally injected into the 10th thoracic spinal cord segment (T10) 7 days before SCI. In addition, nuclear and cytoplasmic extraction and immunofluorescence staining of HO-1 were used to examine the effect of Ad-GFP-HO-1C[INCREMENT]23 on HO-1 nuclear translocation. Evan's blue staining served as an index of capillary permeability and was detected by fluorescence microscopy at 633 nm. Western blotting was also performed to detect tight junction protein expression. The Basso, Beattie and Bresnahan score was used to evaluate kinematic functional recovery through the 28th day after SCI. In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.

Methamphetamine transiently increases the blood-brain barrier permeability in the hippocampus: role of tight junction proteins and matrix metalloproteinase-9.

PubMed

Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Leal, Ermelindo; Milhazes, Nuno; Borges, Fernanda; Ribeiro, Carlos F; Quintela, Oscar; Lendoiro, Elena; López-Rivadulla, Manuel; Ambrósio, António F; Silva, Ana P

2011-09-09

Methamphetamine (METH) is a powerful stimulant drug of abuse that has steadily gained popularity worldwide. It is known that METH is highly neurotoxic and causes irreversible damage of brain cells leading to neurological and psychiatric abnormalities. Recent studies suggested that METH-induced neurotoxicity might also result from its ability to compromise blood-brain barrier (BBB) function. Due to the crucial role of BBB in the maintenance of brain homeostasis and protection against toxic molecules and pathogenic organisms, its dysfunction could have severe consequences. In this study, we investigated the effect of an acute high dose of METH (30mg/kg) on BBB permeability after different time points and in different brain regions. For that, young adult mice were sacrificed 1h, 24h or 72h post-METH administration. METH increased BBB permeability, but this effect was detected only at 24h after administration, being therefore a transitory effect. Interestingly, we also found that the hippocampus was the most susceptible brain region to METH, comparing to frontal cortex and striatum. Moreover, in an attempt to identify the key players in METH-induced BBB dysfunction we further investigated potential alterations in tight junction (TJ) proteins and matrix metalloproteinase-9 (MMP-9). METH was able to decrease the protein levels of zonula occludens (ZO)-1, claudin-5 and occludin in the hippocampus 24h post-injection, and increased the activity and immunoreactivity of MMP-9. The pre-treatment with BB-94 (30mg/kg), a matrix metalloproteinase inhibitor, prevented the METH-induced increase in MMP-9 immunoreactivity in the hippocampus. Overall, the present data demonstrate that METH transiently increases the BBB permeability in the hippocampus, which can be explained by alterations on TJ proteins and MMP-9. Copyright © 2011 Elsevier B.V. All rights reserved.

Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection.

PubMed

Li, Fang; Wang, Yueyun; Yu, Lan; Cao, Shengbo; Wang, Ke; Yuan, Jiaolong; Wang, Chong; Wang, Kunlun; Cui, Min; Fu, Zhen F

2015-05-01

Japanese encephalitis is an acute zoonotic, mosquito-borne disease caused by Japanese encephalitis virus (JEV). Japanese encephalitis is characterized by extensive inflammation in the central nervous system (CNS) and disruption of the blood-brain barrier (BBB). However, the pathogenic mechanisms contributing to the BBB disruption are not known. Here, using a mouse model of intravenous JEV infection, we show that virus titers increased exponentially in the brain from 2 to 5 days postinfection. This was accompanied by an early, dramatic increase in the level of inflammatory cytokines and chemokines in the brain. Enhancement of BBB permeability, however, was not observed until day 4, suggesting that viral entry and the onset of inflammation in the CNS occurred prior to BBB damage. In vitro studies revealed that direct infection with JEV could not induce changes in the permeability of brain microvascular endothelial cell monolayers. However, brain extracts derived from symptomatic JEV-infected mice, but not from mock-infected mice, induced significant permeability of the endothelial monolayer. Consistent with a role for inflammatory mediators in BBB disruption, the administration of gamma interferon-neutralizing antibody ameliorated the enhancement of BBB permeability in JEV-infected mice. Taken together, our data suggest that JEV enters the CNS, propagates in neurons, and induces the production of inflammatory cytokines and chemokines, which result in the disruption of the BBB. Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia, resulting in 70,000 cases each year, in which approximately 20 to 30% of cases are fatal, and a high proportion of patients survive with serious neurological and psychiatric sequelae. Pathologically, JEV infection causes an acute encephalopathy accompanied by BBB dysfunction; however, the mechanism is not clear. Thus, understanding the mechanisms of BBB disruption in JEV infection is important. Our data demonstrate that JEV gains entry into the CNS prior to BBB disruption. Furthermore, it is not JEV infection per se, but the inflammatory cytokines/chemokines induced by JEV infection that inhibit the expression of TJ proteins and ultimately result in the enhancement of BBB permeability. Neutralization of gamma interferon (IFN-γ) ameliorated the enhancement of BBB permeability in JEV-infected mice, suggesting that IFN-γ could be a potential therapeutic target. This study would lead to identification of potential therapeutic avenues for the treatment of JEV infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Mechanism of Bacillus subtilis Spore Inactivation by and Resistance to Supercritical CO2 plus Peracetic Acid

PubMed Central

Setlow, Barbara; Korza, George; Blatt, Kelly M.S.; Fey, Julien P.; Setlow, Peter

2015-01-01

Aims Determine how supercritical CO2 (scCO2) plus peracetic acid (PAA) inactivates Bacillus subtilis spores, factors important in spore resistance to scCO2-PAA, and if spores inactivated by scCO2-PAA are truly dead. Methods and Results Spores of wild-type B. subtilis and isogenic mutants lacking spore protective proteins were treated with scCO2-PAA in liquid or dry at 35°C. Wild-type wet spores (aqueous suspension) were more susceptible than dry spores. Treated spores were examined for viability (and were truly dead), dipicolinic acid (DPA), mutations, permeability to nucleic acid stains, germination under different conditions, energy metabolism and outgrowth. ScCO2-PAA-inactivated spores retained DPA, and survivors had no notable DNA damage. However, DPA was released from inactivated spores at a normally innocuous temperature (85°C), and colony formation from treated spores was salt sensitive. The inactivated spores germinated but did not outgrow, and these germinated spores had altered plasma membrane permeability and defective energy metabolism. Wet or dry coat-defective spores had increased scCO2-PAA sensitivity, and dry spores but not wet spores lacking DNA protective proteins were more scCO2-PAA sensitive. Conclusions These findings suggest that scCO2-PAA inactivates spores by damaging spores’ inner membrane. The spore coat provided scCO2-PAA resistance for both wet and dry spores. DNA protective proteins provided scCO2-PAA resistance only for dry spores. Significance and Impact of Study These results provide information on mechanisms of spore inactivation of and resistance to scCO2-PAA, an agent with increasing use in sterilization applications. PMID:26535794

Mechanism of Bacillus subtilis spore inactivation by and resistance to supercritical CO2 plus peracetic acid.

PubMed

Setlow, B; Korza, G; Blatt, K M S; Fey, J P; Setlow, P

2016-01-01

Determine how supercritical CO2 (scCO2 ) plus peracetic acid (PAA) inactivates Bacillus subtilis spores, factors important in spore resistance to scCO2 -PAA, and if spores inactivated by scCO2 -PAA are truly dead. Spores of wild-type B. subtilis and isogenic mutants lacking spore protective proteins were treated with scCO2 -PAA in liquid or dry at 35°C. Wild-type wet spores (aqueous suspension) were more susceptible than dry spores. Treated spores were examined for viability (and were truly dead), dipicolinic acid (DPA), mutations, permeability to nucleic acid stains, germination under different conditions, energy metabolism and outgrowth. ScCO2 -PAA-inactivated spores retained DPA, and survivors had no notable DNA damage. However, DPA was released from inactivated spores at a normally innocuous temperature (85°C), and colony formation from treated spores was salt sensitive. The inactivated spores germinated but did not outgrow, and these germinated spores had altered plasma membrane permeability and defective energy metabolism. Wet or dry coat-defective spores had increased scCO2 -PAA sensitivity, and dry spores but not wet spores lacking DNA protective proteins were more scCO2 -PAA sensitive. These findings suggest that scCO2 -PAA inactivates spores by damaging spores' inner membrane. The spore coat provided scCO2 -PAA resistance for both wet and dry spores. DNA protective proteins provided scCO2 -PAA resistance only for dry spores. These results provide information on mechanisms of spore inactivation of and resistance to scCO2 -PAA, an agent with increasing use in sterilization applications. © 2015 The Society for Applied Microbiology.

Photodynamic inactivation of conidia of the fungus Colletotrichum abscissum on Citrus sinensis plants with methylene blue under solar radiation.

PubMed

Gonzales, Júlia C; Brancini, Guilherme T P; Rodrigues, Gabriela B; Silva-Junior, Geraldo José; Bachmann, Luciano; Wainwright, Mark; Braga, Gilberto Ú L

2017-11-01

Antimicrobial photodynamic treatment (APDT) is a promising light based approach to control diseases caused by plant-pathogenic fungi. In the present study, we evaluated the effects of APDT with the phenothiazinium photosensitizer methylene blue (MB) under solar radiation on the germination and viability of conidia of the pathogenic fungus Colletotricum abscissum (former Colletotrichum acutatum sensu lato). Experiments were performed both on petals and leaves of sweet orange (Citrus sinensis) in different seasons and weather conditions. Conidial suspensions were deposited on the leaves and petals surface, treated with the PS (25 or 50μM) and exposed to solar radiation for only 30min. The effects of APDT on conidia were evaluated by counting the colony forming units recovered from leaves and petals and by direct evaluating conidial germination on the surface of these plant organs after the treatment. To better understand the mechanistic of conidial photodynamic inactivation, the effect of APDT on the permeability of the conidial plasma membrane was assessed using the fluorescent probe propidium iodide (PI) together with flow cytometry and fluorescence microscopy. APDT with MB and solar exposure killed C. abscissum conidia and prevented their germination on both leaves and petals of citrus. Reduction of conidial viability was up to three orders of magnitude and a complete photodynamic inactivation was achieved in some of the treatments. APDT damaged the conidial plasma membrane and increased its permeability to PI. No damage to sweet orange flowers or leaves was observed after APDT. The demonstration of the efficacy of APDT on the plant host represents a further step towards the use of the method for control phytopathogens in the field. Copyright © 2017 Elsevier B.V. All rights reserved.

Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3beta.

PubMed

Feng, Jianhua; Lucchinetti, Eliana; Ahuja, Preeti; Pasch, Thomas; Perriard, Jean-Claude; Zaugg, Michael

2005-11-01

Postischemic administration of volatile anesthetics activates reperfusion injury salvage kinases and decreases myocardial damage. However, the mechanisms underlying anesthetic postconditioning are unclear. Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane (1.5 minimum alveolar concentration) administered at the onset of reperfusion. In some experiments, atractyloside (10 microm), a mitochondrial permeability transition pore (mPTP) opener, and LY294002 (15 microm), a phosphatidylinositol 3-kinase inhibitor, were coadministered with isoflurane. Western blot analysis was used to determine phosphorylation of protein kinase B/Akt and its downstream target glycogen synthase kinase 3beta after 15 min of reperfusion. Myocardial tissue content of nicotinamide adenine dinucleotide served as a marker for mPTP opening. Accumulation of MitoTracker Red 580 (Molecular Probes, Invitrogen, Basel, Switzerland) was used to visualize mitochondrial function. Anesthetic postconditioning significantly improved functional recovery and decreased infarct size (36 +/- 1% in unprotected hearts vs. 3 +/- 2% in anesthetic postconditioning; P < 0.05). Isoflurane-mediated protection was abolished by atractyloside and LY294002. LY294002 inhibited isoflurane-induced phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta and opened mPTP as determined by nicotinamide adenine dinucleotide measurements. Atractyloside, a direct opener of the mPTP, did not inhibit phosphorylation of protein kinase B/Akt and glycogen synthase kinase 3beta by isoflurane but reversed isoflurane-mediated cytoprotection. Microscopy showed accumulation of the mitochondrial tracker in isoflurane-protected functional mitochondria but no staining in mitochondria of unprotected hearts. Anesthetic postconditioning by isoflurane effectively protects against reperfusion damage by preventing opening of the mPTP through inhibition of glycogen synthase kinase 3beta.

Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3β Signaling and Inhibiting Mitochondrial Permeability Transition

PubMed Central

Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin

2013-01-01

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury. PMID:24058562

Colonic migrating motor complexes are inhibited in acute tri-nitro benzene sulphonic acid colitis.

PubMed

Hofma, Ben R; Wardill, Hannah R; Mavrangelos, Chris; Campaniello, Melissa A; Dimasi, David; Bowen, Joanne M; Smid, Scott D; Bonder, Claudine S; Beckett, Elizabeth A; Hughes, Patrick A

2018-01-01

Inflammatory Bowel Disease (IBD) is characterized by overt inflammation of the intestine and is typically accompanied by symptoms of bloody diarrhea, abdominal pain and cramping. The Colonic Migrating Motor Complex (CMMC) directs the movement of colonic luminal contents over long distances. The tri-nitrobenzene sulphonic acid (TNBS) model of colitis causes inflammatory damage to enteric nerves, however it remains to be determined whether these changes translate to functional outcomes in CMMC activity. We aimed to visualize innate immune cell infiltration into the colon using two-photon laser scanning intra-vital microscopy, and to determine whether CMMC activity is altered in the tri-nitro benzene sulphonic (TNBS) model of colitis. Epithelial barrier permeability was compared between TNBS treated and healthy control mice in-vitro and in-vivo. Innate immune activation was determined by ELISA, flow cytometry and by 2-photon intravital microscopy. The effects of TNBS treatment and IL-1β on CMMC function were determined using a specialized organ bath. TNBS colitis increased epithelial barrier permeability in-vitro and in-vivo. Colonic IL-1β concentrations, colonic and systemic CD11b+ cell infiltration, and the number of migrating CD11b+ cells on colonic blood vessels were all increased in TNBS treated mice relative to controls. CMMC frequency and amplitude were inhibited in the distal and mid colon of TNBS treated mice. CMMC activity was not altered by superfusion with IL-1β. TNBS colitis damages the epithelial barrier and increases innate immune cell activation in the colon and systemically. Innate cell migration into the colon is readily identifiable by two-photon intra-vital microscopy. CMMC are inhibited by inflammation, but this is not due to direct effects of IL-1β.

Natural thermal convection in fractured porous media

NASA Astrophysics Data System (ADS)

Adler, P. M.; Mezon, C.; Mourzenko, V.; Thovert, J. F.; Antoine, R.; Finizola, A.

2015-12-01

In the crust, fractures/faults can provide preferential pathways for fluid flow or act as barriers preventing the flow across these structures. In hydrothermal systems (usually found in fractured rock masses), these discontinuities may play a critical role at various scales, controlling fluid flows and heat transfer. The thermal convection is numerically computed in 3D fluid satured fractured porous media. Fractures are inserted as discrete objects, randomly distributed over a damaged volume, which is a fraction of the total volume. The fluid is assumed to satisfy Darcy's law in the fractures and in the porous medium with exchanges between them. All simulations were made for Rayleigh numbers (Ra) < 150 (hence, the fluid is in thermal equilibrium with the medium), cubic boxes and closed-top conditions. Checks were performed on an unfractured porous medium and the convection cells do start for the theoretical value of Ra, namely 4p². 2D convection was verified up to Ra=800. The influence of parameters such as fracture aperture (or fracture transmissivity), fracture density and fracture length is studied. Moreover, these models are compared to porous media with the same macroscopic permeability. Preliminary results show that the non-uniqueness associated with initial conditions which makes possible either 2D or 3D convection in porous media (Schubert & Straus 1979) is no longer true for fractured porous media (at least for 50

Self-sealing of thermal fatigue and mechanical damage in fiber-reinforced composite materials

NASA Astrophysics Data System (ADS)

Moll, Jericho L.

Fiber reinforced composite tanks provide a promising method of storage for liquid oxygen and hydrogen for aerospace applications. The inherent thermal fatigue of these vessels leads to the formation of microcracks, which allow gas phase leakage across the tank walls. In this dissertation, self-healing functionality is imparted to a structural composite to effectively seal microcracks induced by both mechanical and thermal loading cycles. Two different microencapsulated healing chemistries are investigated in woven glass fiber/epoxy and uni-weave carbon fiber/epoxy composites. Self-healing of mechanically induced damage was first studied in a room temperature cured plain weave E-glass/epoxy composite with encapsulated dicyclopentadiene (DCPD) monomer and wax protected Grubbs' catalyst healing components. A controlled amount of microcracking was introduced through cyclic indentation of opposing surfaces of the composite. The resulting damage zone was proportional to the indentation load. Healing was assessed through the use of a pressure cell apparatus to detect nitrogen flow through the thickness direction of the damaged composite. Successful healing resulted in a perfect seal, with no measurable gas flow. The effect of DCPD microcapsule size (51 microm and 18 microm) and concentration (0--12.2 wt%) on the self-sealing ability was investigated. Composite specimens with 6.5 wt% 51 microm capsules sealed 67% of the time, compared to 13% for the control panels without healing components. A thermally stable, dual microcapsule healing chemistry comprised of silanol terminated poly(dimethyl siloxane) plus a crosslinking agent and a tin catalyst was employed to allow higher composite processing temperatures. The microcapsules were incorporated into a satin weave E-glass fiber/epoxy composite processed at 120°C to yield a glass transition temperature of 127°C. Self-sealing ability after mechanical damage was assessed for different microcapsule sizees (25 microm and 42 microm) and concentrations (0--11 vol%). Incorporating 9 vol% 42 microm capsules or 11 vol% 25 microm capsules into the composite matrix leads to 100% of the samples sealing. The effect of microcapsule concentration on the short beam strength, storage modulus, and glass transition temperature of the composite specimens was also investigated. The thermally stable tin catalyzed poly(dimethyl siloxane) healing chemistry was then integrated into a [0/90]s uniweave carbon fiber/epoxy composite. Thermal cycling (-196°C to 35°C) of these specimens lead to the formation of microcracks, over time, formed a percolating crack network from one side of the composite to the other, resulting in a gas permeable specimen. Crack damage accumulation and sample permeability was monitored with number of cycles for both self-healing and traditional non-healing composites. Crack accumulation occurred at a similar rate for all sample types tested. A 63% increase in lifetime extension was achieved for the self-healing specimens over traditional non-healing composites.

Modelling of the CO2-Induced Degradation of a Fractured Caprock During Leakage: Potential for a Mechanical Self-Limiting Process

NASA Astrophysics Data System (ADS)

Rohmer, J.; Tremosa, J.; Marty, N. C. M.; Audigane, P.

2017-10-01

In the present study, we assess the potential for initiating ductile failure in a fractured caprock due to the chemical alteration of its mechanical properties under pressure increase induced by CO2 leakage and fixed in situ boundary conditions. In this view, 2D numerically coupled reactive-transport simulations were set up by using the Opalinus Clay formation as an analogue for a caprock layer. The fractured system was viewed as a compartmentalised system that consists of a main highly permeable pathway, a moderately permeable damage zone and the intact rock. The outputs of the numerical simulations (mineral fraction, porosity changes, gas saturation, pore-fluid pressure) were converted into parameter changes of the yield surface by viewing the rock material of the three compartments (fault, damage zone and intact rock) as a composite system that consists of a clayey solid material, pores and mineral inclusions (such as carbonate and quartz). Three alteration processes were considered: (1) the effect of the mineral fraction and porosity evolution on the yield surface, (2) changes in the resulting poro-elastic properties and (3) the suction effect, i.e. the bounding effect induced by the presence of two phases, water and CO2. Our numerical investigations showed that the decrease in the friction coefficient remained negligible during leakage, while the pre-consolidation stress mainly decreased. Consequently, the damage zone of the fractured system became more collapsible over time, which was driven by low-to-moderate pressure build-up of the fluid penetrating the fault (1 MPa in our case). For the considered case, the initiation of ductile failure is likely under conditions of fixed vertical stress and zero lateral strain. This process could potentially limit the spatial spreading of CO2-induced alteration, although this remains very site specific. We recommend that characterisation efforts be intensified to obtain better insight into the properties of fracture systems in caprock-like formations (with special attention to their initial over consolidation ratio).

Consequences of the Thermal Transient on the Evolution of the Damaged Zone Around a Repository for Heat-Emitting High-Level Radioactive Waste in a Clay Formation: a Performance Assessment Perspective

NASA Astrophysics Data System (ADS)

Yu, Li; Weetjens, Eef; Sillen, Xavier; Vietor, Tim; Li, Xiangling; Delage, Pierre; Labiouse, Vincent; Charlier, Robert

2014-01-01

A proper evaluation of the perturbations of the host rock induced by the excavation and the emplacement of exothermic wastes is essential for the assessment of the long-term safety of high-level radioactive waste disposals in clay formations. The impact of the thermal transient on the evolution of the damaged zone (DZ) has been explored in the European Commission project TIMODAZ (thermal impact on the damaged zone around a radioactive waste disposal in clay host rocks, 2006-2010). This paper integrates the scientific results of the TIMODAZ project from a performance assessment (PA) point of view, showing how these results support and justify key PA assumptions and the values of PA model parameters. This paper also contextualises the significance of the thermal impact on the DZ from a safety case perspective, highlighting how the project outcomes result into an improved understanding of the thermo-hydro-mechanical behaviour of the clay host rocks. The results obtained in the TIMODAZ project strengthen the assessment basis of the safety evaluation of the current repository designs. There was no evidence throughout the TIMODAZ experimental observations of a temperature-induced additional opening of fractures nor of a significant permeability increase of the DZ. Instead, thermally induced plasticity, swelling and creep seem to be beneficial to the sealing of fractures and to the recovery of a very low permeability in the DZ, close to that of an undisturbed clay host rock. Results from the TIMODAZ project indicate that the favourable properties of the clay host rock, which guarantee the effectiveness of the safety functions of the repository system, are expected to be maintained after the heating-cooling cycle. Hence, the basic assumptions usually made in PA calculations so far are expected to remain valid, and the performance of the system should not be affected in a negative way by the thermal evolution of the DZ around a radioactive waste repository in clay host rock.

Parylene as a new membrane material for BioMEMS applications

NASA Astrophysics Data System (ADS)

Lu, Bo

The work in this thesis aims to use MEMS and microfabrication technologies to develop two types of parylene membrane devices for biomedical applications. The first device is the parylene membrane filter for cancer detection. The presence of circulating tumor cells (CTC) in patient blood is an important sign of cancer metastasis. However, currently there are two big challenges for CTC detection. First, CTCs are extremely rare, especially at the early stage of cancer metastasis. Secondly, CTCs are very fragile, and are very likely to be damaged during the capturing process. By using size-based membrane filtration through the specially designed parylene filters, together with a constant-pressure filtration system, we are able to capture the CTCs from patient blood with high capture efficiency, high viability, moderate enrichment, and high throughput. Both immunofluorescence enumeration and telomerase activity detection have been used to detect and differentiate the captured CTCs. The feasibility of further cell culture of the captured CTCs has also been demonstrated, which could be a useful way to increase the number of CTCs for future studies. Models of the time-dependent cell membrane damage are developed to predict and prevent CTC damage during this detection process. The results of clinical trials further demonstrate that the parylene membrane filter is a promising device for cancer detection. The second device is the parylene artificial Bruch's membrane for age-related macular degeneration (AMD). AMD is usually characterized by an impaired Bruch's membrane with much lowered permeability, which impedes the transportation of nutrients from choroid vessels to nourish the retinal pigment epithelial (RPE) cells and photoreceptors. Parylene is selected as a substitute material because of its good mechanical properties, transparency, biocompatibility, and machinability. More importantly, it is found that the permeability of submicron parylene is very similar to that of healthy human Bruch's membrane. A mesh-supported submicron parylene membrane structure has been designed and its feasibility as an artificial Bruch's membrane has been demonstrated by diffusion experiments, cell perfusion culture, and pressure deflection tests. RPE cells are able to adhere, proliferate and develop into normal in vivo-like morphology and functions. Currently this artificial membrane is under clinical trials.

2D Simulations of Earthquake Cycles at a Subduction Zone Based on a Rate and State Friction Law -Effects of Pore Fluid Pressure Changes-

NASA Astrophysics Data System (ADS)

Mitsui, Y.; Hirahara, K.

2006-12-01

There have been a lot of studies that simulate large earthquakes occurring quasi-periodically at a subduction zone, based on the laboratory-derived rate-and-state friction law [eg. Kato and Hirasawa (1997), Hirose and Hirahara (2002)]. All of them assume that pore fluid pressure in the fault zone is constant. However, in the fault zone, pore fluid pressure changes suddenly, due to coseismic pore dilatation [Marone (1990)] and thermal pressurization [Mase and Smith (1987)]. If pore fluid pressure drops and effective normal stress rises, fault slip is decelerated. Inversely, if pore fluid pressure rises and effective normal stress drops, fault slip is accelerated. The effect of pore fluid may cause slow slip events and low-frequency tremor [Kodaira et al. (2004), Shelly et al. (2006)]. For a simple spring model, how pore dilatation affects slip instability was investigated [Segall and Rice (1995), Sleep (1995)]. When the rate of the slip becomes high, pore dilatation occurs and pore pressure drops, and the rate of the slip is restrained. Then the inflow of pore fluid recovers the pore pressure. We execute 2D earthquake cycle simulations at a subduction zone, taking into account such changes of pore fluid pressure following Segall and Rice (1995), in addition to the numerical scheme in Kato and Hirasawa (1997). We do not adopt hydrostatic pore pressure but excess pore pressure for initial condition, because upflow of dehydrated water seems to exist at a subduction zone. In our model, pore fluid is confined to the fault damage zone and flows along the plate interface. The smaller the flow rate is, the later pore pressure recovers. Since effective normal stress keeps larger, the fault slip is decelerated and stress drop becomes smaller. Therefore the smaller flow rate along the fault zone leads to the shorter earthquake recurrence time. Thus, not only the frictional parameters and the subduction rate but also the fault zone permeability affects the recurrence time of earthquake cycle. Further, the existence of heterogeneity in the permeability along the plate interface can bring about other slip behaviors, such as slow slip events. Our simulations indicate that, in addition to the frictional parameters, the permeability within the fault damage zone is one of essential parameters, which controls the whole earthquake cycle.

Using estimated risk to develop stimulation strategies for induced seismicity in enhanced geothermal systems

NASA Astrophysics Data System (ADS)

Douglas, John; Aochi, Hideo

2014-05-01

Enhanced Geothermal Systems (EGS) are an attractive source of low-carbon electricity and heating. Consequently, a number of tests of this technology have been made during the past couple of decades and various projects are being planned or under development. EGS work by the injection of fluid into deep boreholes to increase permeability and hence allow the circulation and heating of fluid through a geothermal reservoir. Permeability is irreversibly increased by the shearing of pre-existing factures or fault segments, and hence by the generation of microseismicity. One aspect of this technology that can cause public concern and consequently could limit the widespread adoption of EGS within populated areas is the risk of generating earthquakes that are sufficiently large to be felt (or even to cause building damage). Therefore, there is a need to balance stimulation and exploitation of the geothermal reservoir by injecting fluids against the pressing requirement to keep the earthquake risk below an acceptable level. Current strategies to balance these potentially conflicting requirements rely on a traffic light system based on the observed magnitudes of the triggered earthquakes and the measured peak ground velocities from these events. Douglas and Aochi (Pageoph, 2014) propose an alternative system that uses the actual risk of generating felt (or damaging) earthquake ground motions at a site of interest (e.g. a nearby town) to control the injection rate. This risk is computed by combining characteristics of the observed seismicity rate of the previous six hours, with a (potentially site-specific) ground-motion prediction equation to obtain a real-time seismic hazard curve, and then the convolution of this with the derivative of a (potentially site-specific) fragility curve. Based on the relation between computed risk and pre-defined acceptable risk thresholds the injection is: increased (if the risk is below the amber level), decreased (if the risk is between amber and red levels) or stopped completely (if the risk is above the red level). Based on simulations using a recently developed model of induced seismicity in geothermal systems (Aochi et al., GJI, 2014), which is validated here using observations from the Basel EGS in 2006, it is shown that the proposed procedure could lead to both acceptable levels of risk and increased permeability.

Citral exerts its antifungal activity against Penicillium digitatum by affecting the mitochondrial morphology and function.

PubMed

Zheng, Shiju; Jing, Guoxing; Wang, Xiao; Ouyang, Qiuli; Jia, Lei; Tao, Nengguo

2015-07-01

This work investigated the effect of citral on the mitochondrial morphology and function of Penicillium digitatum. Citral at concentrations of 2.0 or 4.0 μL/mL strongly damaged mitochondria of test pathogen by causing the loss of matrix and increase of irregular mitochondria. The deformation extent of the mitochondria of P. digitatum enhanced with increasing concentrations of citral, as evidenced by a decrease in intracellular ATP content and an increase in extracellular ATP content of P. digitatum cells. Oxygen consumption showed that citral resulted in an inhibition in the tricarboxylic acid cycle (TCA) pathway of P. digitatum cells, induced a decrease in activities of citrate synthetase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinodehydrogenase and the content of citric acid, while enhancing the activity of malic dehydrogenase in P. digitatum cells. Our present results indicated that citral could damage the mitochondrial membrane permeability and disrupt the TCA pathway of P. digitatum. Copyright © 2015 Elsevier Ltd. All rights reserved.

Managing heat and immune stress in athletes with evidence-based strategies.

PubMed

Pyne, David B; Guy, Joshua H; Edwards, Andrew M

2014-09-01

Heat and immune stress can affect athletes in a wide range of sports and environmental conditions. The classical thermoregulatory model of heat stress has been well characterized, as has a wide range of practical strategies largely centered on cooling and heat-acclimation training. In the last decade evidence has emerged of an inflammatory pathway that can also contribute to heat stress. Studies are now addressing the complex and dynamic interplay between hyperthermia, the coagulation cascade, and a systemic inflammatory response occurring after transient damage to the gastrointestinal tract. Damage to the intestinal mucosal membrane increases permeability, resulting in leakage of endotoxins into the circulation. Practical strategies that target both thermoregulatory and inflammatory causes of heat stress include precooling; short-term heat-acclimation training; nutritional countermeasures including hydration, energy replacement, and probiotic supplementation; pacing strategies during events; and postevent cooling measures. Cooperation between international, national, and local sporting organizations is required to ensure that heat-management policies and strategies are implemented effectively to promote athletes' well-being and performance.

Resveratrol induces membrane and DNA disruption via pro-oxidant activity against Salmonella typhimurium.

PubMed

Lee, Wonjong; Lee, Dong Gun

2017-07-22

Resveratrol is a flavonoid found in various plants including grapes, which has been reported to be active against various pathogenic bacteria. However, antibacterial effects and mechanisms via pro-oxidant property of resveratrol remain unknown and speculative. This research investigated antibacterial mechanism of resveratrol against a food-borne human pathogen Salmonella typhimurium, and confirmed the cell death associated oxidative damage. Resveratrol increased outer membrane permeability and membrane depolarization. It also was observed DNA injury responses such as DNA fragmentation, increasing DNA contents and cell division inhibition. Intracellular ROS accumulation, GSH depletion and significant increased malondialdehyde levels were confirmed, which indicated pro-oxidant activity of resveratrol and oxidative stress. Furthermore, the observed lethal damages were reduced by antioxidant N-acetylcysteine treatment supported the view that resveratrol-induced oxidative stress stimulated S. typhimurium cell death. In conclusion, this study expands understanding on role of pro-oxidant property and insight into previously unrecognized oxygen-dependent anti-Salmonella mechanism on resveratrol. Copyright © 2017 Elsevier Inc. All rights reserved.

The role and importance of porosity in the deflagration rates of HMX-based materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glascoe, E A; Hsu, P C; Springer, H K

The deflagration behavior of thermally damaged HMX-based materials will be discussed. Strands of material were burned at pressures ranging from 10-300 MPa using the LLNL high pressure strand burner. Strands were heated in-situ and burned while still hot; temperatures range from 90-200 C and were chosen in order to allow for thermal damage of the material without significant decomposition of the HMX. The results indicate that multiple variables affect the burn rate but the most important are the polymorph of HMX and the nature and thermal stability of the non-HE portion of the material. Characterization of the strands indicate thatmore » the thermal soak produces significant porosity and permeability in the sample allowing for significantly faster burning due to the increased surface area and new pathways for flame spread into the material. Specifically, the deflagration rates of heated PBXN-9, LX-10, and PBX-9501 will be discussed and compared.« less

High Content Analysis technology for evaluating the joint toxicity of sunset yellow and sodium sulfite in vitro.

PubMed

Qu, Daofeng; Gu, Yanpei; Feng, Lifang; Han, Jianzhong

2017-10-15

Foods contain various additives that affect our daily lives. At present, food additive safety evaluation standards are based on the toxicity of single additives, but food additives are often used in combination and may have additive, synergistic or antagonistic actions. The current study investigated the toxicity of food additives and mechanisms of damage in HepG2 cells using High Content Analysis (HCA). We used the CCK-8 assay to determine cell viability, providing an experimental basis for determining the safety of food additives. All of the food additives tested were observed to decrease the growth of HepG2 cells in a dose-dependent manner. Sunset yellow and sodium sulfite had IC50 values of 1.06, and 0.30g/L at 24h, respectively. HCA showed that both sunset yellow and sodium sulfite had synergistic effects on cell number, membrane permeability, mitochondrial membrane potential, intracellular calcium level, oxidative stress, and high dose group DNA damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.

PubMed

Wang, Wei-Wei; Zhang, Yu; Huang, Xiao-Bing; You, Nan; Zheng, Lu; Li, Jing

2017-10-14

To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl 4 )-induced acute hepatic dysfunction. A rat model of HE was established with CCl 4 . Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined. FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment. FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Role of Staphylococcus aureus Virulence Factors in Inducing Inflammation and Vascular Permeability in a Mouse Model of Bacterial Endophthalmitis

PubMed Central

Kumar, Ajay; Kumar, Ashok

2015-01-01

Staphylococcus (S.) aureus is a common causative agent of bacterial endophthalmitis, a vision threatening complication of eye surgeries. The relative contribution of S. aureus virulence factors in the pathogenesis of endophthalmitis remains unclear. Here, we comprehensively analyzed the development of intraocular inflammation, vascular permeability, and the loss of retinal function in C57BL/6 mouse eyes, challenged with live S. aureus, heat-killed S. aureus (HKSA), peptidoglycan (PGN), lipoteichoic acid (LTA), staphylococcal protein A (SPA), α-toxin, and Toxic-shock syndrome toxin 1 (TSST1). Our data showed a dose-dependent (range 0.01 μg/eye to 1.0 μg/eye) increase in the levels of inflammatory mediators by all virulence factors. The cell wall components, particularly PGN and LTA, seem to induce higher levels of TNF-α, IL-6, KC, and MIP2, whereas the toxins induced IL-1β. Similarly, among the virulence factors, PGN induced higher PMN infiltration. The vascular permeability assay revealed significant leakage in eyes challenged with live SA (12-fold) and HKSA (7.3-fold), in comparison to other virulence factors (~2-fold) and controls. These changes coincided with retinal tissue damage, as evidenced by histological analysis. The electroretinogram (ERG) analysis revealed a significant decline in retinal function in eyes inoculated with live SA, followed by HKSA, SPA, and α-toxin. Together, these findings demonstrate the differential innate responses of the retina to S. aureus virulence factors, which contribute to intraocular inflammation and retinal function loss in endophthalmitis. PMID:26053426

Uropathogenic E. coli Promote a Paracellular Urothelial Barrier Defect Characterized by Altered Tight Junction Integrity, Epithelial Cell Sloughing and Cytokine Release

PubMed Central

Wood, M. W.; Breitschwerdt, E. B.; Nordone, S. K.; Linder, K. E.; Gookin, J. L.

2013-01-01

Summary The urinary bladder is a common site of bacterial infection with a majority of cases attributed to uropathogenic Escherichia coli. Sequels of urinary tract infections (UTIs) include the loss of urothelial barrier function and subsequent clinical morbidity secondary to the permeation of urine potassium, urea and ammonia into the subepithelium. To date there has been limited research describing the mechanism by which this urothelial permeability defect develops. The present study models acute uropathogenic E. coli infection in vitro using intact canine bladder mucosa mounted in Ussing chambers to determine whether infection induces primarily a transcellular or paracellular permeability defect. The Ussing chamber sustains tissue viability while physically separating submucosal and lumen influences, so this model is ideal for quantitative measurement of transepithelial electrical resistance (TER) to assess alterations of urothelial barrier function. Using this model, changes in both tissue ultrastructure and TER indicated that uropathogenic E. coli infection promotes a paracellular permeability defect associated with the failure of umbrella cell tight junction formation and umbrella cell sloughing. In addition, bacterial interaction with the urothelium promoted secretion of cytokines from the urinary bladder with bioactivity capable of modulating epithelial barrier function including tumour necrosis factor-α, interleukin (IL)-6 and IL-15. IL-15 secretion by the infected bladder mucosa is a novel finding and, because IL-15 plays key roles in reconstitution of tight junction function in damaged intestine, this study points to a potential role for IL-15 in UTI-induced urothelial injury. PMID:22014415

PAF involvement in dermal extravasation in the reverse passive Arthus reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deacon, R.W.; Melden, M.K.; Saunders, R.N.

The reverse passive erthus reaction (RPAR) is characterized by PMN infiltration, increased vascular permeability leading to plasma extravasation and vessel damage. In the skin RPAR is an inflammatory response initiated by deposition of immune complexes and attributed to complement activation. As PAF can elicit similar dermal reactions, they examined the PAF antagonist SRI 63-072 in the RPAR. Guinea pigs were given an i.v. injection of /sup 125/I-BSA (Ag-20 mg/kg with 20 mg/kg Evan's blue as a permeability tracer), followed by intradermal (i.d.) injections (0.1 ml/site) of anti-BSA antibodies (Ab). After 30 min, dermal sites (2 cm diam.) were removed, countedmore » and the ..mu..l plasma/site (over background counts) calculated from plasma radioactivity measurements. The plasma leakage (..mu..l plasma/site) was dose-dependent upon Ab dose (6-200 ..mu..g/site). At the ultrastructural level, the presence of neutrophils and eosinophils were observed in the extravascular spaces. The luminal endothelium exhibited cytotoxic characteristics and loss of junctional integrity. SRI 63-072 exhibited 50% maximal inhibition when given i.d. with the Ab (0.1 ..mu..g/site) but only 5-10% when given at 3.0 mg/kg i.v. with Ag. No further inhibition of dermal extravasation was observed using SRI 63-441, a competitive receptor antagonist with 3-30 fold the in vivo potency of SRI 63-072. As dermal extravasation in RPAR is only partially inhibited by a PAF antagonist, it appears that other vasoactive mediators, possibly histamine, may be influencing vessel permeability as well.« less

Inhibition of free radical scavenging enzymes affects mitochondrial membrane permeability transition during growth and aging of yeast cells.

PubMed

Deryabina, Yulia; Isakova, Elena; Sekova, Varvara; Antipov, Alexey; Saris, Nils-Erik L

2014-12-01

In this study, we investigated the change in the antioxidant enzymes activity, cell respiration, reactive oxygen species (ROS), and impairment of membrane mitochondria permeability in the Endomyces magnusii yeasts during culture growth and aging. We showed that the transition into stationary phase is the key tool to understanding interaction of these processes. This growth stage is distinguished by two-fold increase in ROS production and respiration rate as compared to those in the logarithmic phase. It results in induction of alternative oxidase (AO) in the stationary phase, decline of the main antioxidant enzymes activities, ROS-production, and mitochondria membrane permeability. Significant increase in the share of mitochondrial isoform of superoxide dismutase (SOD2) occurred in the stationary phase from 51.8% (24 h of cultivation) to 68.6% (48 h of cultivation). Upon blocking the essential ROS-scavenging enzymes, SODs and catalases (CATs) some heterogeneity of cell population was observed: 80-90% of cells displayed evident signs of early apoptosis (such as disorientation of mitochondria cristae, mitochondrial fragmentation and deformation of nuclear chromatine). However, 10-20% of the population were definitely healthy. It allowed to draw the conclusion that a complete system of cell antioxidant protection underlies normal mitochondria functioning while the E. magnusii yeasts grow and age. Moreover, this system provides unimpaired cell physiology under oxidative stress during culture aging in the stationary phase. Failures in mitochondria functions due to inhibition of ROS-scavenging enzymes of CATs and SODs could lead to damage of the cells and some signs of early apoptosis.

[Effect of lanthanum on the flavonoids contents and antioxidant capacity in soybean seedling under ultraviolet-B stress].

PubMed

Peng, Qi; Zhou, Qing

2008-07-01

Dynamic state of antioxidant capacity of flavonoids was investigated for a further demonstration of alleviating the damage of the UV-B radiation in the La-treated soybean seedlings under UV-B stress. Using hydroponics culture, the effects of lanthanum on the contents of flavonoids and its ability of antioxidant under elevated ultraviolet-B radiation (280-320 nm) was studied in this paper. The results showed flavonoids contents in Soybean seedlings during the stress and convalescent period increase firstly and then reduce. Membrane permeability and MDA contents increase firstly (1st-5th day) and then fall (6th to 11th day). A similar change of flavonoids contents and clearance of flavonoids scavenging O2*- and *OH in soybean seedlings occur; the flavonoids contents La(III) + UV-B > UV-B > La(III) > CK, La(III) + T1 > La(III) + T2. Plasma membrane permeability and MAD contents UV-B> La(III) + UV-B > CK > La(III), La(III) + T2 > La(III) + T1. The ability of Scavenging activities of free radical (O2*-, *OH) La(III) + UV-B > UV-B > La(III) > CK. It suggested that the regulative effect of La(III) on flavonoids, improved the metabolism of ROS, diminished the concentration of MDA and maintained normal Plasma membrane permeability, and that its protective effect against low UV-B radiation was superior to that of high UV-B radiation. To conclude, the defensive effect of La(III) on soybean seedlings under UV-B stress was carried out on the layer of defense system.

Borneol, a novel agent that improves central nervous system drug delivery by enhancing blood-brain barrier permeability.

PubMed

Zhang, Qun-Lin; Fu, Bingmei M; Zhang, Zhang-Jin

2017-11-01

The clinical application of central nervous system (CNS) drugs is limited by their poor bioavailability due to the blood-brain barrier (BBB). Borneol is a naturally occurring compound in a class of 'orifice-opening' agents often used for resuscitative purposes in traditional Chinese medicine. A growing body of evidence confirms that the 'orifice-opening' effect of borneol is principally derived from opening the BBB. Borneol is therefore believed to be an effective adjuvant that can improve drug delivery to the brain. The purpose of this paper is to provide a comprehensive review of information accumulated over the past two decades on borneol's chemical features, sources, toxic and kinetic profiles, enhancing effects on BBB permeability and their putative mechanisms, improvements in CNS drug delivery, and pharmaceutical forms. The BBB-opening effect of borneol is a reversible physiological process characterized by rapid and transient penetration of the BBB and highly specific brain regional distribution. Borneol also protects the structural integrity of the BBB against pathological damage. The enhancement of the BBB permeability is associated with the modulation of multiple ATP-binding cassette transporters, including P-glycoprotein; tight junction proteins; and predominant enhancement of vasodilatory neurotransmitters. Systemic co-administration with borneol improves drug delivery to the brain in a region-, dose- and time-dependent manner. Several pharmaceutical forms of borneol have been developed to improve the kinetic and toxic profiles of co-administered drugs and enhance their delivery to the brain. Borneol is a promising novel agent that deserves further development as a BBB permeation enhancer for CNS drug delivery.

TSAR User’s Manual-A Program for Assessing the Effects of Conventional and Chemical Attacks on Sortie Generation: Volume 2, Data Input, Program Operation and Redimensioning, and Sample Problem,

DTIC Science & Technology

1990-09-01

by damage. SHPREP When not zero, all parts repaired at an operating base are shipped to the base that is selected with the SEND logic in the CONTRL ...nominal (at rest) skin temperature when each MOPP is worn, the pumping factor (y), the insulation factor (CLO), and the permeability factor (IM). The...temiperature is taken to be 35 0C, and 36"C for MOPP #5; the pumping factor (y) ranges from 0.200 to 0.270, the insulation factor (CLO) from 1.70 to

The use of subsurface thermal data, isotopic tracers and earthquake hypocenter locations to unravel deep regional flow systems within the crystalline basement beneath the Rio Grande rift, New Mexico. (Invited)

NASA Astrophysics Data System (ADS)

Person, M. A.; Woolsey, E.; Pepin, J.; Crossey, L. J.; Karlstrom, K. E.; Phillips, F. M.; Kelley, S.; Timmons, S.

2013-12-01

The Rio Grande rift in New Mexico hosts a number of low-temperature geothermal systems as well as the 19 km deep Socorro Magma Body. The presence of a mantle helium anomaly measured at San Acacia spring (3He/4He = 0.295 RA) and in an adjacent shallow well (50m < ; 0.8 RA) overlying the Socorro Magma Body at the southern terminus of the Albuquerque Basin suggests that deeply sourced fluids mix with the sedimentary basin groundwater flow system. Temperatures recorded at the base of the San Acacia well is elevated (29 oC). Published estimates of uplift rates and heat flow suggest that the magma body was emplaced about 1-3 ka and reflects a long-lived (several Ma) magmatic system. Further south near the southern terminus of the Engle Basin, much warmer temperatures (42 oC) occur at shallow depths within the spa district in the town of Truth or Consequences at shallow depths also suggesting deep-fluid circulation. 14C constrained apparent groundwater residence times in the spa district range between 6-10 ka. We have developed two 6-19 km deep crustal-scale, cross-sectional models that simulate subsurface fluid flow, heat and isotope (3He/4He) transport as well as groundwater residence times along the Rio Grande rift. The North-South oriented model of the Albuquerque Basin incorporates a high-permeability conduit 100 m wide having hydrologic properties differing from surrounding crystalline basement units. We use these models to constrain the crustal permeability structure and fluid circulation patterns beneath the Albuquerque and Engle Basins. Model results are compared to measurements of groundwater temperatures, residence times (14C), and 3He/4He data. We also use the distribution of earthquake hypocenters to constrain likely fault-crystalline basement hydraulic interactions in the seismogenic crust above the Socorro Magma Body. For the case of the southern Albuquerque Basin, conduit permeability associated with the Indian Hill conduit/fault zone must range between about 1.0E-13 to 1.0E-15 m2 in order for simulated 3He/4He, solute concentrations, and temperatures to match observed conditions. Basement permeability outside of the fault damage zone must range between 1.0E-17 to 1.0E-18 m2. However, a much longer transport time is required (between about 20-30 ka) in order to match observed conditions suggesting multiple magmatic intrusion events. For the case of the Engle Basin near Truth or Consequences, bulk crustal permeability between a depth of 2-6 km below the sedimentary succession must approach 1.0E-12 m2 in order to reproduce hot spring temperatures and groundwater residence times. We compare these model derived permeability estimates to published permeability-depth relationships for crustal rocks (Manning and Ingebritsen, 1999; Ingebritsen and Manning, 2010).

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

PubMed Central

Rinsma, Nicolaas F.; Farré, Ricard; Troost, Fred J.; Elizalde, Montserrat; Keszthelyi, Daniel; Helyes, Zsuzsanna; Masclee, Ad A.; Conchillo, José M.

2017-01-01

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients. PMID:28534850

Horseradish Peroxidase-Encapsulated Hollow Silica Nanospheres for Intracellular Sensing of Reactive Oxygen Species

NASA Astrophysics Data System (ADS)

Chen, Hsin-Yi; Wu, Si-Han; Chen, Chien-Tsu; Chen, Yi-Ping; Chang, Feng-Peng; Chien, Fan-Ching; Mou, Chung-Yuan

2018-04-01

Reactive oxygen species (ROS) have crucial roles in cell signaling and homeostasis. Overproduction of ROS can induce oxidative damage to various biomolecules and cellular structures. Therefore, developing an approach capable of monitoring and quantifying ROS in living cells is significant for physiology and clinical diagnoses. Some cell-permeable fluorogenic probes developed are useful for the detection of ROS while in conjunction with horseradish peroxidase (HRP). Their intracellular scenario is however hindered by the membrane-impermeable property of enzymes. Herein, a new approach for intracellular sensing of ROS by using horseradish peroxidase-encapsulated hollow silica nanospheres (designated HRP@HSNs), with satisfactory catalytic activity, cell membrane permeability, and biocompatibility, was prepared via a microemulsion method. These HRP@HSNs, combined with selective probes or targeting ligands, could be foreseen as ROS-detecting tools in specific organelles or cell types. As such, dihydrorhodamine 123-coupled HRP@HSNs were used for the qualitative and semi-quantitative analysis of physiological H2O2 levels in activated RAW 264.7 macrophages. We envision that this HSNs encapsulating active enzymes can be conjugated with selective probes and targeting ligands to detect ROS in specific organelles or cell types of interest.

Increased Uptake of Chelated Copper Ions by Lolium perenne Attributed to Amplified Membrane and Endodermal Damage

PubMed Central

Johnson, Anthea; Singhal, Naresh

2015-01-01

The contributions of mechanisms by which chelators influence metal translocation to plant shoot tissues are analyzed using a combination of numerical modelling and physical experiments. The model distinguishes between apoplastic and symplastic pathways of water and solute movement. It also includes the barrier effects of the endodermis and plasma membrane. Simulations are used to assess transport pathways for free and chelated metals, identifying mechanisms involved in chelate-enhanced phytoextraction. Hypothesized transport mechanisms and parameters specific to amendment treatments are estimated, with simulated results compared to experimental data. Parameter values for each amendment treatment are estimated based on literature and experimental values, and used for model calibration and simulation of amendment influences on solute transport pathways and mechanisms. Modeling indicates that chelation alters the pathways for Cu transport. For free ions, Cu transport to leaf tissue can be described using purely apoplastic or transcellular pathways. For strong chelators (ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA)), transport by the purely apoplastic pathway is insufficient to represent measured Cu transport to leaf tissue. Consistent with experimental observations, increased membrane permeability is required for simulating translocation in EDTA and DTPA treatments. Increasing the membrane permeability is key to enhancing phytoextraction efficiency. PMID:26512647

Selective Permeability of Uranyl Peroxide Nanocages to Different Alkali Ions: Influences from Surface Pores and Hydration Shells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Yunyi; Haso, Fadi; Szymanowski, Jennifer E. S.

2015-11-16

The precise guidance to different ions across the biological channels is essential for many biological processes. An artificial nanopore system will facilitate the study of the ion-transport mechanism through nanosized channels and offer new views for designing nanodevices. Herein we reveal that a 2.5 nm-sized, fullerene-shaped molecular cluster Li48+mK12(OH)m[UO2(O2)(OH)]60-(H2O)n (m≈20 and n≈310) (U60) shows selective permeability to different alkali ions. The subnanometer pores on the water–ligand-rich surface of U60 are able to block Rb+ and Cs+ ions from passing through, while allowing Na+ and K+ ions, which possess larger hydrated sizes, to enter the interior space of U60. An interestinglymore » high entropy gain during the binding process between U60 and alkali ions suggests that the hydration shells of Na+/K+ and U60 are damaged during the interaction. The ion selectivity of U60 is greatly influenced by both the morphologies of the surface nanopores and the dynamics of the hydration shells.« less

Fault architecture and deformation processes within poorly lithified rift sediments, Central Greece

NASA Astrophysics Data System (ADS)

Loveless, Sian; Bense, Victor; Turner, Jenni

2011-11-01

Deformation mechanisms and resultant fault architecture are primary controls on the permeability of faults in poorly lithified sediments. We characterise fault architecture using outcrop studies, hand samples, thin sections and grain-size data from a minor (1-10 m displacement) normal-fault array exposed within Gulf of Corinth rift sediments, Central Greece. These faults are dominated by mixed zones with poorly developed fault cores and damage zones. In poorly lithified sediment deformation is distributed across the mixed zone as beds are entrained and smeared. We find particulate flow aided by limited distributed cataclasis to be the primary deformation mechanism. Deformation may be localised in more competent sediments. Stratigraphic variations in sediment competency, and the subsequent alternating distributed and localised strain causes complexities within the mixed zone such as undeformed blocks or lenses of cohesive sediment, or asperities at the mixed zone/protolith boundary. Fault tip bifurcation and asperity removal are important processes in the evolution of these fault zones. Our results indicate that fault zone architecture and thus permeability is controlled by a range of factors including lithology, stratigraphy, cementation history and fault evolution, and that minor faults in poorly lithified sediment may significantly impact subsurface fluid flow.

Geochemical and microstructural evidence for interseismic changes in fault zone permeability and strength, Alpine Fault, New Zealand

NASA Astrophysics Data System (ADS)

Boulton, Carolyn; Menzies, Catriona D.; Toy, Virginia G.; Townend, John; Sutherland, Rupert

2017-01-01

Oblique dextral motion on the central Alpine Fault in the last circa 5 Ma has exhumed garnet-oligoclase facies mylonitic fault rocks from ˜35 km depth. During exhumation, deformation, accompanied by fluid infiltration, has generated complex lithological variations in fault-related rocks retrieved during Deep Fault Drilling Project (DFDP-1) drilling at Gaunt Creek, South Island, New Zealand. Lithological, geochemical, and mineralogical results reveal that the fault comprises a core of highly comminuted cataclasites and fault gouges bounded by a damage zone containing cataclasites, protocataclasites, and fractured mylonites. The fault core-alteration zone extends ˜20-30 m from the principal slip zone (PSZ) and is characterized by alteration of primary phases to phyllosilicate minerals. Alteration associated with distinct mineral phases occurred proximal the brittle-to-plastic transition (T ≤ 300-400°C, 6-10 km depth) and at shallow depths (T = 20-150°C, 0-3 km depth). Within the fault core-alteration zone, fractures have been sealed by precipitation of calcite and phyllosilicates. This sealing has decreased fault normal permeability and increased rock mass competency, potentially promoting interseismic strain buildup.

STUDIES ON THE MECHANISM OF EXPERIMENTAL PROTEINURIA INDUCED BY RENIN

PubMed Central

Deodhar, Sharad D.; Cuppage, Francis E.; Gableman, E.

1964-01-01

Renin-induced proteinuria in the rat was investigated, with special emphasis on the relationship between the enzymatic activity and the proteinuric effect of renin. The dependence of the proteinuric effect on the enzymatic activity was shown by using (a) renin preparations of widely varying purity and (b) chemically modified "active" and "inactive" renin derivatives. Angiotensin II, the pressor product of the enzymatic action of renin, also produced significant proteinuria. Adrenalectomy abolished the proteinuria induced by renin. Proteinuria, however, occurred as a result of pretreatment with DOCA, or aldosterone, or without treatment, 7 to 8 weeks after adrenalectomy. Electron microscopic studies of the kidney at the time of maximal proteinuria showed focal flattening and fusion of epithelial foot processes, as well as swelling and vesicle formation in endothelial and epithelial cells of the glomeruli. Studies with intravenously injected saccharated iron oxide showed increased permeability of the glomerular capillary basement membrane to these particles. These changes were transient and were not seen 24 hours after renin injection. Adrenalectomy prevented these changes. It is concluded that renin, acting through angiotensin, causes glomerular capillary damage with increased permeability of these structures to protein and resultant proteinuria. The adrenal glands participate in a permissive role in this phenomenon. PMID:14212126

Loopless nontrapping invasion-percolation model for fracking.

PubMed

Norris, J Quinn; Turcotte, Donald L; Rundle, John B

2014-02-01

Recent developments in hydraulic fracturing (fracking) have enabled the recovery of large quantities of natural gas and oil from old, low-permeability shales. These developments include a change from low-volume, high-viscosity fluid injection to high-volume, low-viscosity injection. The injected fluid introduces distributed damage that provides fracture permeability for the extraction of the gas and oil. In order to model this process, we utilize a loopless nontrapping invasion percolation previously introduced to model optimal polymers in a strongly disordered medium and for determining minimum energy spanning trees on a lattice. We performed numerical simulations on a two-dimensional square lattice and find significant differences from other percolation models. Additionally, we find that the growing fracture network satisfies both Horton-Strahler and Tokunaga network statistics. As with other invasion percolation models, our model displays burst dynamics, in which the cluster extends rapidly into a connected region. We introduce an alternative definition of bursts to be a consecutive series of opened bonds whose strengths are all below a specified value. Using this definition of bursts, we find good agreement with a power-law frequency-area distribution. These results are generally consistent with the observed distribution of microseismicity observed during a high-volume frack.

Electrochemical Impedance Spectroscopy for Real-Time Detection of Lipid Membrane Damage Based on a Porous Self-Assembly Monolayer Support.

PubMed

Zhang, Meng; Zhai, Qingyu; Wan, Liping; Chen, Li; Peng, Yu; Deng, Chunyan; Xiang, Juan; Yan, Jiawei

2018-06-19

Layer-by-layer dissolution and permeable pore formation are two typical membrane damage pathways, which induce membrane function disorder and result in serious disease, such as Alzheimer's disease, Keshan disease, Sickle-cell disease, and so on. To effectively distinguish and sensitively monitor these two typical membrane damage pathways, a facile electrochemical impedance strategy was developed on a porous self-assembly monolayer (pSAM) supported bilayer lipid membrane (BLM). The pSAM was prepared by selectively electrochemical reductive desorption of the mercaptopropionic acid in a mixed mercaptopropionic acid/11-mercaptoundecanoic acid self-assembled monolayer, which created plenty of nanopores with tens of nanometers in diameter and several nanometers in height (defined as inner-pores). The ultralow aspect ratio of the inner-pores was advantageous to the mass transfer of electrochemical probe [Fe(CN) 6 ] 3-/4- , simplifying the equivalent electric circuit for electrochemical impedance spectroscopy analysis at the electrode/membrane interface. [Fe(CN) 6 ] 3-/4- transferring from the bulk solution into the inner-pore induce significant changes of the interfacial impedance properties, improving the detection sensitivity. Based on these, the different membrane damage pathways were effectively distinguished and sensitively monitored with the normalized resistance-capacitance changes of inner-pore-related parameters including the electrolyte resistance within the pore length ( R pore ) and the metal/inner-pore interfacial capacitance ( C pore ) and the charge-transfer resistance ( R ct-in ) at the metal/inner-pore interface.

Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

PubMed

Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

2017-11-22

Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

The behavior of peroxisomes in vitro: mammalian peroxisomes are osmotically sensitive particles.

PubMed

Antonenkov, Vasily D; Sormunen, Raija T; Hiltunen, J Kalervo

2004-12-01

It has been known for a long time that mammalian peroxisomes are extremely fragile in vitro. Changes in the morphological appearance and leakage of proteins from purified particles demonstrate that peroxisomes are damaged during isolation. However, some properties of purified peroxisomes, e.g., the latency of catalase, imply that their membranes are not disrupted. In the current study, we tried to ascertain the mechanism of this unusual behavior of peroxisomes in vitro. Biochemical and morphological examination of isolated peroxisomes subjected to sonication or to freezing and thawing showed that the membrane of the particles seals after disruption, restoring permeability properties. Transient damage of the membrane leads to the formation of peroxisomal "ghosts" containing nucleoid but nearly devoid of matrix proteins. The rate of leakage of matrix proteins from broken particles depended inversely on their molecular size. The effect of polyethylene glycols on peroxisomal integrity indicated that these particles are osmotically sensitive. Peroxisomes suffered an osmotic lysis during isolation that was resistant to commonly used low-molecular-mass osmoprotectors, e.g., sucrose. Damage to peroxisomes was partially prevented by applying more "bulky" osmoprotectors, e.g., polyethylene glycol 1500. A method was developed for the isolation of highly purified and nearly intact peroxisomes from rat liver by using polyethylene glycol 1500 as an osmoprotector.

Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

PubMed

Hernández-Esquivel, Luz; Pavón, Natalia; Buelna-Chontal, Mabel; González-Pacheco, Héctor; Belmont, Javier; Chávez, Edmundo

2015-06-01

Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury

PubMed Central

Fakhruddin, Selim; Alanazi, Wael

2017-01-01

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage. Interestingly, all these pathological changes are predominantly driven by diabetes-induced reactive oxygen species (ROS) and abnormal downstream signaling molecules. In diabetic kidney, NADPH oxidase (enzymatic) and mitochondrial electron transport chain (nonenzymatic) are the prominent sources of ROS, which are believed to cause the onset of albuminuria followed by progression to renal damage through podocyte depletion. Chronic hyperglycemia and consequent ROS production can trigger abnormal signaling pathways involving diverse signaling mediators such as transcription factors, inflammatory cytokines, chemokines, and vasoactive substances. Persistently, increased expression and activation of these signaling molecules contribute to the irreversible functional and structural changes in the kidney resulting in critically decreased glomerular filtration rate leading to eventual renal failure. PMID:28164134

Modelling biofilm-induced formation damage and biocide treatment in subsurface geosystems

PubMed Central

Ezeuko, C C; Sen, A; Gates, I D

2013-01-01

Biofilm growth in subsurface porous media, and its treatment with biocides (antimicrobial agents), involves a complex interaction of biogeochemical processes which provide non-trivial mathematical modelling challenges. Although there are literature reports of mathematical models to evaluate biofilm tolerance to biocides, none of these models have investigated biocide treatment of biofilms growing in interconnected porous media with flow. In this paper, we present a numerical investigation using a pore network model of biofilm growth, formation damage and biocide treatment. The model includes three phases (aqueous, adsorbed biofilm, and solid matrix), a single growth-limiting nutrient and a single biocide dissolved in the water. Biofilm is assumed to contain a single species of microbe, in which each cell can be a viable persister, a viable non-persister, or non-viable (dead). Persisters describe small subpopulation of cells which are tolerant to biocide treatment. Biofilm tolerance to biocide treatment is regulated by persister cells and includes ‘innate’ and ‘biocide-induced’ factors. Simulations demonstrate that biofilm tolerance to biocides can increase with biofilm maturity, and that biocide treatment alone does not reverse biofilm-induced formation damage. Also, a successful application of biological permeability conformance treatment involving geologic layers with flow communication is more complicated than simply engineering the attachment of biofilm-forming cells at desired sites. PMID:23164434

The influence of hair bleach on the ultrastructure of human hair with special reference to hair damage.

PubMed

Imai, Takehito

2011-05-01

The influence of human hair bleaching agents with different bleaching strength on the ultrastructure of human hair was studied using a transmission electron microscope (TEM) and an energy dispersive X-ray spectrometer equipped with TEM (EDS-TEM). Two kinds of bleaching agents were used: a lightener agent with a weak bleaching effect and a powder-bleach with a stronger bleaching effect. From the comparison of the bleaching properties obtained by the electronic staining of black and white hair samples, it was suggested that the permeability of hair was increased by bleaching, and there was an increase of the stainability of hair subjected to electronic staining. The bleaching action provoked the decomposition of melanin granules and the flow out of granular contents into the intermacrofibrillar matrix. Some metal elements were detected in the melanin granular matrix by EDS-TEM. As a result, the diffusion of metal elements into the intermacrofibrillar matrix promoted further damage to the hair by catalytic action with the hydrogen peroxide in the bleaching agents outside the melanin granules. Further study will lead us to the edge of the development of a new bleaching agent, which reacts only with melanin granules and causes the minimum of damage to outside the melanin granules.

Lycopene Prevents Amyloid [Beta]-Induced Mitochondrial Oxidative Stress and Dysfunctions in Cultured Rat Cortical Neurons.

PubMed

Qu, Mingyue; Jiang, Zheng; Liao, Yuanxiang; Song, Zhenyao; Nan, Xinzhong

2016-06-01

Brains affected by Alzheimer's disease (AD) show a large spectrum of mitochondrial alterations at both morphological and genetic level. The causal link between β-amyloid (Aβ) and mitochondrial dysfunction has been established in cellular models of AD. We observed previously that lycopene, a member of the carotenoid family of phytochemicals, could counteract neuronal apoptosis and cell damage induced by Aβ and other neurotoxic substances, and that this neuroprotective action somehow involved the mitochondria. The present study aims to investigate the effects of lycopene on mitochondria in cultured rat cortical neurons exposed to Aβ. It was found that lycopene attenuated Aβ-induced oxidative stress, as evidenced by the decreased intracellular reactive oxygen species generation and mitochondria-derived superoxide production. Additionally, lycopene ameliorated Aβ-induced mitochondrial morphological alteration, opening of the mitochondrial permeability transition pores and the consequent cytochrome c release. Lycopene also improved mitochondrial complex activities and restored ATP levels in Aβ-treated neuron. Furthermore, lycopene prevented mitochondrial DNA damages and improved the protein level of mitochondrial transcription factor A in mitochondria. Those results indicate that lycopene protects mitochondria against Aβ-induced damages, at least in part by inhibiting mitochondrial oxidative stress and improving mitochondrial function. These beneficial effects of lycopene may account for its protection against Aβ-induced neurotoxicity.

Origin of Permeability and Structure of Flows in Fractured Media

NASA Astrophysics Data System (ADS)

De Dreuzy, J.; Darcel, C.; Davy, P.; Erhel, J.; Le Goc, R.; Maillot, J.; Meheust, Y.; Pichot, G.; Poirriez, B.

2013-12-01

After more than three decades of research, flows in fractured media have been shown to result from multi-scale geological structures. Flows result non-exclusively from the damage zone of the large faults, from the percolation within denser networks of smaller fractures, from the aperture heterogeneity within the fracture planes and from some remaining permeability within the matrix. While the effect of each of these causes has been studied independently, global assessments of the main determinisms is still needed. We propose a general approach to determine the geological structures responsible for flows, their permeability and their organization based on field data and numerical modeling [de Dreuzy et al., 2012b]. Multi-scale synthetic networks are reconstructed from field data and simplified mechanical modeling [Davy et al., 2010]. High-performance numerical methods are developed to comply with the specificities of the geometry and physical properties of the fractured media [Pichot et al., 2010; Pichot et al., 2012]. And, based on a large Monte-Carlo sampling, we determine the key determinisms of fractured permeability and flows (Figure). We illustrate our approach on the respective influence of fracture apertures and fracture correlation patterns at large scale. We show the potential role of fracture intersections, so far overlooked between the fracture and the network scales. We also demonstrate how fracture correlations reduce the bulk fracture permeability. Using this analysis, we highlight the need for more specific in-situ characterization of fracture flow structures. Fracture modeling and characterization are necessary to meet the new requirements of a growing number of applications where fractures appear both as potential advantages to enhance permeability and drawbacks for safety, e.g. in energy storage, stimulated geothermal energy and non-conventional gas productions. References Davy, P., et al. (2010), A likely universal model of fracture scaling and its consequence for crustal hydromechanics, Journal of Geophysical Research-Solid Earth, 115, 13. de Dreuzy, J.-R., et al. (2012a), Influence of fracture scale heterogeneity on the flow properties of three-dimensional Discrete Fracture Networks (DFN), J. Geophys. Res.-Earth Surf., 117(B11207), 21 PP. de Dreuzy, J.-R., et al. (2012b), Synthetic benchmark for modeling flow in 3D fractured media, Computers and Geosciences(0). Pichot, G., et al. (2010), A Mixed Hybrid Mortar Method for solving flow in Discrete Fracture Networks, Applicable Analysis, 89(10), 1729-1643. Pichot, G., et al. (2012), Flow simulation in 3D multi-scale fractured networks using non-matching meshes, SIAM Journal on Scientific Computing (SISC), 34(1). Figure: (a) Fracture network with a broad-range of fracture lengths. (b) Flows (log-scale) with homogeneous fractures. (c) Flows (log-scale) with heterogeneous fractures [de Dreuzy et al., 2012a]. The impact of the fracture apertures (c) is illustrated on the organization of flows.

Petrophysical, Geochemical, and Hydrological Evidence for Extensive Fracture-Mediated Fluid and Heat Transport in the Alpine Fault's Hanging-Wall Damage Zone

NASA Astrophysics Data System (ADS)

Townend, John; Sutherland, Rupert; Toy, Virginia G.; Doan, Mai-Linh; Célérier, Bernard; Massiot, Cécile; Coussens, Jamie; Jeppson, Tamara; Janku-Capova, Lucie; Remaud, Léa.; Upton, Phaedra; Schmitt, Douglas R.; Pezard, Philippe; Williams, Jack; Allen, Michael John; Baratin, Laura-May; Barth, Nicolas; Becroft, Leeza; Boese, Carolin M.; Boulton, Carolyn; Broderick, Neil; Carpenter, Brett; Chamberlain, Calum J.; Cooper, Alan; Coutts, Ashley; Cox, Simon C.; Craw, Lisa; Eccles, Jennifer D.; Faulkner, Dan; Grieve, Jason; Grochowski, Julia; Gulley, Anton; Hartog, Arthur; Henry, Gilles; Howarth, Jamie; Jacobs, Katrina; Kato, Naoki; Keys, Steven; Kirilova, Martina; Kometani, Yusuke; Langridge, Rob; Lin, Weiren; Little, Tim; Lukacs, Adrienn; Mallyon, Deirdre; Mariani, Elisabetta; Mathewson, Loren; Melosh, Ben; Menzies, Catriona; Moore, Jo; Morales, Luis; Mori, Hiroshi; Niemeijer, André; Nishikawa, Osamu; Nitsch, Olivier; Paris, Jehanne; Prior, David J.; Sauer, Katrina; Savage, Martha K.; Schleicher, Anja; Shigematsu, Norio; Taylor-Offord, Sam; Teagle, Damon; Tobin, Harold; Valdez, Robert; Weaver, Konrad; Wiersberg, Thomas; Zimmer, Martin

2017-12-01

Fault rock assemblages reflect interaction between deformation, stress, temperature, fluid, and chemical regimes on distinct spatial and temporal scales at various positions in the crust. Here we interpret measurements made in the hanging-wall of the Alpine Fault during the second stage of the Deep Fault Drilling Project (DFDP-2). We present observational evidence for extensive fracturing and high hanging-wall hydraulic conductivity (˜10-9 to 10-7 m/s, corresponding to permeability of ˜10-16 to 10-14 m2) extending several hundred meters from the fault's principal slip zone. Mud losses, gas chemistry anomalies, and petrophysical data indicate that a subset of fractures intersected by the borehole are capable of transmitting fluid volumes of several cubic meters on time scales of hours. DFDP-2 observations and other data suggest that this hydrogeologically active portion of the fault zone in the hanging-wall is several kilometers wide in the uppermost crust. This finding is consistent with numerical models of earthquake rupture and off-fault damage. We conclude that the mechanically and hydrogeologically active part of the Alpine Fault is a more dynamic and extensive feature than commonly described in models based on exhumed faults. We propose that the hydrogeologically active damage zone of the Alpine Fault and other large active faults in areas of high topographic relief can be subdivided into an inner zone in which damage is controlled principally by earthquake rupture processes and an outer zone in which damage reflects coseismic shaking, strain accumulation and release on interseismic timescales, and inherited fracturing related to exhumation.

Effect of Mucuna pruriens on oxidative stress mediated damage in aged rat sperm.

PubMed

Suresh, Sekar; Prithiviraj, Elumalai; Prakash, Seppan

2010-02-01

Mucuna pruriens Linn., a leguminous plant, has been recognized as an aphrodisiac and spermatogenic agent. Protective efficacy of M. pruriens on reactive oxygen species (ROS)-induced pathophysiological alterations in structural and functional integrity of epididymal sperm in aged Wister albino rat was analysed. Animals were grouped as groups I, II, III and IV, i.e. young (control), aged, aged treated with ethanolic extract (200 mg/kg b.w.) of M. pruriens and young rats treated with M. pruriens, respectively. At the end of the experimental period, i.e. after 60 days animals were sacrificed, epididymal sperm were collected and subjected to count, viability, motility, morphology and morphometric analysis. Enzymatic and non-enzymatic antioxidants, ROS, lipid peroxidation (LPO), DNA damage, chromosomal integrity and mitochondrial membrane potential were estimated. Results obtained from the aged animals showed significant reduction in sperm count, viability and motility, increased morphological damage and an increase in the number of sperm with cytoplasmic remnant, and these alterations were significantly reversed in M. pruriens treated group. Significant increase in LPO, HO and H(2)O(2) production and significant decline in the levels of the enzymatic and non-enzymatic antioxidants were observed in the aged animals. Supplementation of M. pruriens significantly reduced ROS and LPO production and significant increase in both enzymatic and non-enzymatic antioxidant levels. There were significant DNA damage, loss of chromosomal integrity and increase in mitochondrial membrane permeability in aged rat sperm. This was significantly reduced in group III. Present observation indicates the antioxidant enhancing property, free radical quenching ability and spermatogenic efficacy of the M. pruriens. Collectively, sperm damage in ageing was significantly reduced by quenching ROS, improving antioxidant defence system and mitochondrial function.

Approach to the vadose zone monitoring in hazardous and solid waste disposal facilities

NASA Astrophysics Data System (ADS)

Twardowska, Irena

2004-03-01

In the solid waste (SW)disposal sites, in particular at the unlined facilities, at the remediated or newly-constructed units equipped with novel protective/reactive permeable barriers or at lined facilities with leachate collection systems that are prone to failure, the vadose zone monitoring should comprise besides the natural soil layer beneath the landfill, also the anthropogenic vadose zone, i.e. the waste layer and pore solutions in the landfill. The vadose zone screening along the vertical profile of SW facilities with use of direct invasive soil-core and soil-pore liquid techniques shows vertical downward redistribution of inorganic (macroconstituents and heavy metals) and organic (PAHs) contaminant loads in water infiltrating through the waste layer. These loads can make ground water down-gradient of the dump unfit for any use. To avoid damage of protective/reactive permeable barriers and liners, an installation of stationary monitoring systems along the waste layer profile during the construction of a landfill, which are amenable to generate accurate data and information in a near-real time should be considered including:(i) permanent samplers of pore solution, with a periodic pump-induced transport of collected solution to the surface, preferably with instant field measurements;(ii)chemical sensors with continuous registration of critical parameters. These techniques would definitely provide an early alert in case when the chemical composition of pore solution percolating downward the waste profile shows unfavorable transformations, which indicate an excessive contaminant load approaching ground water. The problems concerning invasive and stationary monitoring of the vadose zone in SW disposal facilities will be discussed at the background of results of monitoring data and properties of permeable protective/reactive barriers considered for use.

Zinc irreversibly damages major enzymes of energy production and antioxidant defense prior to mitochondrial permeability transition.

PubMed

Gazaryan, Irina G; Krasinskaya, Inna P; Kristal, Bruce S; Brown, Abraham M

2007-08-17

Recent observations point to the role played by Zn2+ as an inducer of neuronal death. Two Zn2+ targets have been identified that result in inhibition of mitochondrial respiration: the bc1 center and, more recently, alpha-ketoglutarate dehydrogenase. Zn2+ is also a mediator of oxidative stress, leading to mitochondrial failure, release of apoptotic peptides, and neuronal death. We now present evidence, by means of direct biochemical assays, that Zn2+ is imported through the Ca2+ uniporter and directly targets major enzymes of energy production (lipoamide dehydrogenase) and antioxidant defense (thioredoxin reductase and glutathione reductase). We demonstrate the following. (a) These matrix enzymes are rapidly inhibited by application of Zn2+ to intact mitochondria. (b) Delayed treatment with membrane-impermeable chelators has no effect, indicating rapid transport of biologically relevant quantities of Zn2+ into the matrix. (c) Membrane-permeable chelators stop but do not reverse enzyme inactivation. (d) Enzyme inhibition is rapid and irreversible and precedes the major changes associated with the mitochondrial permeability transition (MPT). (e) The extent and rate of enzyme inactivation linearly correlates with the MPT onset and propagation. (f) The Ca2+ uniporter blocker, Ruthenium Red, protects enzyme activities and delays pore opening up to 2 microm Zn2+. An additional, unidentified import route functions at higher Zn2+ concentrations. (g) No enzyme inactivation is observed for Ca2+-induced MPT. These observations strongly suggest that, unlike Ca2+, exogenous Zn2+ interferes with mitochondrial NADH production and directly alters redox protection in the matrix, contributing to mitochondrial dysfunction. Inactivation of these enzymes by Zn2+ is irreversible, and thus only their de novo synthesis can restore function, which may underlie persistent loss of oxidative carbohydrate metabolism following transient ischemia.

Hypertonic Saline Reduces Vascular Leakage in a Mouse Model of Severe Dengue

PubMed Central

Tan, Kar Wai; Angeli, Veronique; Moochhala, Shabbir; Ooi, Eng Eong; Alonso, Sylvie

2013-01-01

Dengue (DEN) is a mosquito-borne viral disease and represents a serious public health threat and an economical burden throughout the tropics. Dengue clinical manifestations range from mild acute febrile illness to severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS). Currently, resuscitation with large volumes of isotonic fluid remains the gold standard of care for DEN patients who develop vascular leakage and shock. Here, we investigated the ability of small volume of hypertonic saline (HTS) suspensions to control vascular permeability in a mouse model of severe DEN associated with vascular leakage. Several HTS treatment regimens were considered and our results indicated that a single bolus of 7.5% NaCl at 4 mL per kg of body weight administered at the onset of detectable vascular leakage rapidly and significantly reduced vascular leak for several days after injection. This transient reduction of vascular leakage correlated with reduced intestine and liver damage with restoration of the hepatic functions, and resulted in delayed death of the infected animals. Mechanistically, we showed that HTS did not directly impact on the viral titers but resulted in lower immune cells counts and decreased systemic levels of soluble mediators involved in vascular permeability. In addition, we demonstrated that neutrophils do not play a critical role in DEN-associated vascular leakage and that the therapeutic effect of HTS is not mediated by its impact on the neutrophil counts. Together our data indicate that HTS treatment can transiently but rapidly reduce dengue-associated vascular leakage, and support the findings of a recent clinical trial which evaluated the efficacy of a hypertonic suspension to impact on vascular permeability in DSS children. PMID:23637867

Predicting Large-scale Effects During Cookoff of Plastic-Bonded Explosives (PBX 9501 PBX 9502 and LX-14)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hobbs, Michael L.; Kaneshige, Michael J.; Erikson, William W.

In this study, we have made reasonable cookoff predictions of large-scale explosive systems by using pressure-dependent kinetics determined from small-scale experiments. Scale-up is determined by properly accounting for pressure generated from gaseous decomposition products and the volume that these reactive gases occupy, e.g. trapped within the explosive, the system, or vented. The pressure effect on the decomposition rates has been determined for different explosives by using both vented and sealed experiments at low densities. Low-density explosives are usually permeable to decomposition gases and can be used in both vented and sealed configurations to determine pressure-dependent reaction rates. In contrast, explosivesmore » that are near the theoretical maximum density (TMD) are not as permeable to decomposition gases, and pressure-dependent kinetics are difficult to determine. Ignition in explosives at high densities can be predicted by using pressure-dependent rates determined from the low-density experiments as long as gas volume changes associated with bulk thermal expansion are also considered. In the current work, cookoff of the plastic-bonded explosives PBX 9501 and PBX 9502 is reviewed and new experimental work on LX-14 is presented. Reactive gases are formed inside these heated explosives causing large internal pressures. The pressure is released differently for each of these explosives. For PBX 9501, permeability is increased and internal pressure is relieved as the nitroplasticizer melts and decomposes. Internal pressure in PBX 9502 is relieved as the material is damaged by cracks and spalling. For LX-14, internal pressure is not relieved until the explosive thermally ignites. The current paper is an extension of work presented at the 26th ICDERS symposium [1].« less

New continuous-flow total artificial heart and vascular permeability.

PubMed

Feng, Jun; Cohn, William E; Parnis, Steven M; Sodha, Neel R; Clements, Richard T; Sellke, Nicholas; Frazier, O Howard; Sellke, Frank W

2015-12-01

We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of monascin on hematoma clearance and edema after intracerebral hemorrhage in rats.

PubMed

Wang, Juan; Wang, Gaiqing; Yi, Jinying; Xu, Yi; Duan, Shuna; Li, Tong; Sun, Xin-Gang; Dong, Liang

2017-09-01

Intracerebral hemorrhage (ICH) is a particularly devastating form of stroke with high mortality and morbidity. Hematomas are the primary cause of neurologic deficits associated with ICH. The products of hematoma are recognized as neurotoxins and the main contributors to edema formation and tissue damage after ICH. Finding a means to efficiently promote absorption of hematoma is a novel clinical challenge for ICH. Peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2), had been shown that, can take potential roles in the endogenous hematoma clearance. However, monascin, a novel natural Nrf2 activator with PPARγ agonist, has not been reported to play a role in ICH. This study was designed to evaluate the effect of monascin on neurological deficits, hematoma clearance and edema extinction in a model of ICH in rats. 164 adult male Sprague-Dawley (SD) rats were randomly divided into sham; vehicle; monascin groups with low dosages (1mg/kg/day), middle dosages (5mg/kg/day) and high dosages (10mg/kg/day) respectively. Animals were euthanized at 1, 3 and 7days following neurological evaluation after surgery. We examined the effect of monascin on the brain water contents, blood brain barrier (BBB) permeability and hemoglobin levels, meanwhile reassessed the volume of hematoma and edema around the hematoma by Magnetic Resonance Imaging (MRI) in each group. The high dosage of monascin significantly improved neurological deficits, reduced the volume of hematoma in 1-7days after ICH, decreased BBB permeability and edema formation in 1-3days following ICH. Our study demonstrated that the high dosage of monascin played a neuroprotective role in ICH through reducing BBB permeability, edema and hematoma volume. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders.

PubMed

DosSantos, Marcos F; Holanda-Afonso, Rosenilde C; Lima, Rodrigo L; DaSilva, Alexandre F; Moura-Neto, Vivaldo

2014-01-01

The function of the blood-brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood-spinal cord barrier and blood-nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine.

The role of the blood–brain barrier in the development and treatment of migraine and other pain disorders

PubMed Central

DosSantos, Marcos F.; Holanda-Afonso, Rosenilde C.; Lima, Rodrigo L.; DaSilva, Alexandre F.; Moura-Neto, Vivaldo

2014-01-01

The function of the blood–brain barrier (BBB) related to chronic pain has been explored for its classical role in regulating the transcellular and paracellular transport, thus controlling the flow of drugs that act at the central nervous system, such as opioid analgesics (e.g., morphine) and non-steroidal anti-inflammatory drugs. Nonetheless, recent studies have raised the possibility that changes in the BBB permeability might be associated with chronic pain. For instance, changes in the relative amounts of occludin isoforms, resulting in significant increases in the BBB permeability, have been demonstrated after inflammatory hyperalgesia. Furthermore, inflammatory pain produces structural changes in the P-glycoprotein, the major efflux transporter at the BBB. One possible explanation for these findings is the action of substances typically released at the site of peripheral injuries that could lead to changes in the brain endothelial permeability, including substance P, calcitonin gene-related peptide, and interleukin-1 beta. Interestingly, inflammatory pain also results in microglial activation, which potentiates the BBB damage. In fact, astrocytes and microglia play a critical role in maintaining the BBB integrity and the activation of those cells is considered a key mechanism underlying chronic pain. Despite the recent advances in the understanding of BBB function in pain development as well as its interference in the efficacy of analgesic drugs, there remain unknowns regarding the molecular mechanisms involved in this process. In this review, we explore the connection between the BBB as well as the blood–spinal cord barrier and blood–nerve barrier, and pain, focusing on cellular and molecular mechanisms of BBB permeabilization induced by inflammatory or neuropathic pain and migraine. PMID:25339863

The harmful effects of ethanol on ion transport and cellular respiration.

PubMed

Blachley, J D; Johnson, J H; Knochel, J P

1985-01-01

The deleterious effects of ethanol on a variety of tissues may result largely from altered ion permeabilities and transport. Clinically relevant ethanol concentrations in blood increase the sodium permeability of the plasma membrane and depress active sodium transport by suppressing Na, K-ATPase activity. As a result, intracellular sodium concentration increases. The total tissue content of calcium increases. Important transport mechanisms deranged by ethanol probably include those regulating calcium-sodium and hydrogen-sodium exchange at the plasma membrane and calcium uptake by the sarcoplasmic reticulum. A modest decline in magnesium content of muscle occurs after chronic exposure to ethanol. This also has been associated with accumulation of calcium. After days to weeks of sustained ethanol intake, sodium pump activity, active sodium transport and tissue oxygen consumption increase. The cell membrane potential, initially lowered by alcohol, increases to supraphysiological levels. This is likely an electrogenic effect of increased sodium transport in response to a sodium leak. Eventually the earlier derangements in tissue composition, including retention of sodium, chloride, and calcium, and reductions in magnesium, potassium, and phosphate, slowly undergo correction. This biphasic response of injury and adaptation appears to depend upon adequate nutrition and the absence of other factors that can adversely affect cell function. That the Na, K-ATPase activity and oxygen consumption remain elevated suggests an ongoing sodium leak of the sarcolemmal membrane. Chronic ethanol-induced cell necrosis may be related to the increased intracellular calcium that accompanies the increase in sodium permeability. Conceivably, critically elevated concentrations of calcium in the cytoplasm may activate autolytic enzymes that in turn may be responsible for structural damage to the cell.

Antioxidant capacity of flavonoid in soybean seedlings under the joint actions of rare earth element La(III) and ultraviolet-B stress.

PubMed

Peng, Qi; Zhou, Qing

2009-01-01

The dynamic state of antioxidant capacity of flavonoid was investigated for a further demonstration of alleviating the damage of the ultraviolet (UV)-B radiation in the La-treated soybean seedlings under UV-B stress. Using hydroponics culture, the effects of lanthanum on the contents of flavonoid and its ability of antioxidant under elevated ultraviolet-B radiation (280-320 nm) was studied. The results showed flavonoid content in soybean seedlings with UV-B treatment during the stress and convalescent period was increased initially and then decreased, compared with control. Membrane permeability and MDA contents increase at first (first to fifth day) and then decrease (6th-11th day). A similar change of flavonoid content and clearance of flavonoid scavenging O2- and *OH in soybean seedlings occurred. Flavonoid content and ability of flavonoid scavenging O2- and *OH in soybean seedlings with La(III) + UV-B treatment were higher than those of UV-B treatment. Meanwhile, membrane permeability and MDA contents in soybean seedlings were lower than those of UV-B treatment. Compared with control, phenylalanine content in soybean seedlings with UV-B treatment is depressed, phenylalanine content in soybean seedlings with La(III) treatment was enhanced. However, phenylalanine content in La(III) + UV-B treatment is not decreased but slightly increased, compared with UV-B treatment. It suggested that the regulative effect of La(III) of the optimum concentration on flavonoid improved the metabolism of ROS, diminished the concentration of MDA and maintained normal plasma membrane permeability, and that its protective effect against low UV-B radiation is superior to that of high UV-B radiation. The defensive effect of La(III) on soybean seedlings under UV-B stress is carried out on the layer of defense system.

Geomechanical Response of Jointed Caprock During CO2 Geological Sequestration

NASA Astrophysics Data System (ADS)

Newell, P.; Martinez, M. J.; Bishop, J. E.

2014-12-01

Geological sequestration of CO2 refers to the injection of supercritical CO2 into deep reservoirs trapped beneath a low-permeability caprock formation. Maintaining caprock integrity during the injection process is the most important factor for a successful injection. In this work we evaluate the potential for jointed caprock during injection scenarios using coupled three-dimensional multiphase flow and geomechanics modeling. Evaluation of jointed/fractured caprock systems is of particular concern to CO2 sequestration because creation or reactivation of joints (mechanical damage) can lead to enhanced pathways for leakage. In this work, we use an equivalent continuum approach to account for the joints within the caprock. Joint's aperture and non-linear stiffness of the caprock will be updated dynamically based on the effective normal stress. Effective permeability field will be updated based on the joints' aperture creating an anisotropic permeability field throughout the caprock. This feature would add another coupling between the solid and fluid in addition to basic Terzaghi's effective stress concept. In this study, we evaluate the impact of the joint's orientation and geometry of caprock and reservoir layers on geomechanical response of the CO2 geological systems. This work is supported as part of the Center for Frontiers of Subsurface Energy Security, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Award Number DE-SC0001114. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Permeability and flammability study of composite sandwich structures for cryogenic applications

NASA Astrophysics Data System (ADS)

Bubacz, Monika

Fiber reinforced plastics offer advantageous specific strength and stiffness compared to metals and has been identified as candidates for the reusable space transportation systems primary structures including cryogenic tanks. A number of carbon and aramid fiber reinforced plastics have been considered for the liquid hydrogen tanks. Materials selection is based upon mechanical properties and containment performance (long and short term) and upon manufacturing considerations. The liquid hydrogen tank carries shear, torque, end load, and bending moment due to gusts, maneuver, take-off, landing, lift, drag, and fuel sloshing. The tank is pressurized to about 1.5 atmosphere (14.6psi or 0.1 MPa) differential pressure and on ascent maintains the liquid hydrogen at a temperature of 20K. The objective of the research effort into lay the foundation for developing the technology required for reliable prediction of the effects of various design, manufacturing, and service parameters on the susceptibility of composite tanks to develop excessive permeability to cryogenic fuels. Efforts will be expended on developing the materials and structural concepts for the cryogenic tanks that can meet the functional requirements. This will include consideration for double wall composite sandwich structures, with inner wall to meet the cryogenic requirements. The structure will incorporate nanoparticles for properties modifications and developing barriers. The main effort will be extended to tank wall's internal skin design. The main requirements for internal composite stack are: (1) introduction of barrier film (e.g. honeycomb material paper sheet) to reduce the wall permeability to hydrogen, (2) introduction of nanoparticles into laminate resin to prevent micro-cracking or crack propagation. There is a need to characterize and analyze composite sandwich structural damage due to burning and explosion. Better understanding of the flammability and blast resistance of the composite structures needs to be evaluated.

Red blood cell membrane water permeability increases with length of ex vivo storage.

PubMed

Alshalani, Abdulrahman; Acker, Jason P

2017-06-01

Water transport across the red blood cell (RBC) membrane is an essential cell function that needs to be preserved during ex vivo storage. Progressive biochemical depletion during storage can result in significant conformational and compositional changes to the membrane. Characterizing the changes to RBC water permeability can help in evaluating the quality of stored blood products and aid in the development of improved methods for the cryopreservation of red blood cells. This study aimed to characterize the water permeability (L p ), osmotically inactive fraction (b), and Arrhenius activation energy (E a ) at defined storage time-points throughout storage and to correlate the observed results with other in vitro RBC quality parameters. RBCs were collected from age- and sex-matched blood donors. A stopped flow spectrophotometer was used to determine L p and b by monitoring changes in hemoglobin autofluorescence when RBCs were exposed to anisotonic solutions. Experimental values of L p were characterized at three different temperatures (4, 20 and 37 °C) to determine the E a . Results showed that L p , b, and E a of stored RBCs significantly increase by day 21 of storage. Degradation of the RBC membrane with length of storage was seen as an increase in hemolysis and supernatant potassium, and a decrease in deformability, mean corpuscular hemoglobin concentration and supernatant sodium. RBC osmotic characteristics were shown to change with storage and correlate with changes in RBC membrane quality metrics. Monitoring water parameters is a predictor of membrane damage and loss of membrane integrity in ex vivo stored RBCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke.

PubMed

Asadi, Yasin; Gorjipour, Fazel; Behrouzifar, Sedigheh; Vakili, Abedin

2018-06-07

Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood-brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 µg/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice.

Temperature and composition of carbonate cements record early structural control on cementation in a nascent deformation band fault zone: Moab Fault, Utah, USA

NASA Astrophysics Data System (ADS)

Hodson, Keith R.; Crider, Juliet G.; Huntington, Katharine W.

2016-10-01

Fluid-driven cementation and diagenesis within fault zones can influence host rock permeability and rheology, affecting subsequent fluid migration and rock strength. However, there are few constraints on the feedbacks between diagenetic conditions and structural deformation. We investigate the cementation history of a fault-intersection zone on the Moab Fault, a well-studied fault system within the exhumed reservoir rocks of the Paradox Basin, Utah, USA. The fault zone hosts brittle structures recording different stages of deformation, including joints and two types of deformation bands. Using stable isotopes of carbon and oxygen, clumped isotope thermometry, and cathodoluminescence, we identify distinct source fluid compositions for the carbonate cements within the fault damage zone. Each source fluid is associated with different carbonate precipitation temperatures, luminescence characteristics, and styles of structural deformation. Luminescent carbonates appear to be derived from meteoric waters mixing with an organic-rich or magmatic carbon source. These cements have warm precipitation temperatures and are closely associated with jointing, capitalizing on increases in permeability associated with fracturing during faulting and subsequent exhumation. Earlier-formed non-luminescent carbonates have source fluid compositions similar to marine waters, low precipitation temperatures, and are closely associated with deformation bands. The deformation bands formed at shallow depths very early in the burial history, preconditioning the rock for fracturing and associated increases in permeability. Carbonate clumped isotope temperatures allow us to associate structural and diagenetic features with burial history, revealing that structural controls on fluid distribution are established early in the evolution of the host rock and fault zone, before the onset of major displacement.

Activation of VEGF/Flk-1-ERK Pathway Induced Blood-Brain Barrier Injury After Microwave Exposure.

PubMed

Wang, Li-Feng; Li, Xiang; Gao, Ya-Bing; Wang, Shui-Ming; Zhao, Li; Dong, Ji; Yao, Bin-Wei; Xu, Xin-Ping; Chang, Gong-Min; Zhou, Hong-Mei; Hu, Xiang-Jun; Peng, Rui-Yun

2015-08-01

Microwaves have been suggested to induce neuronal injury and increase permeability of the blood-brain barrier (BBB), but the mechanism remains unknown. The role of the vascular endothelial growth factor (VEGF)/Flk-1-Raf/MAPK kinase (MEK)/extracellular-regulated protein kinase (ERK) pathway in structural and functional injury of the blood-brain barrier (BBB) following microwave exposure was examined. An in vitro BBB model composed of the ECV304 cell line and primary rat cerebral astrocytes was exposed to microwave radiation (50 mW/cm(2), 5 min). The structure was observed by scanning electron microscopy (SEM) and the permeability was assessed by measuring transendothelial electrical resistance (TEER) and horseradish peroxidase (HRP) transmission. Activity and expression of VEGF/Flk-1-ERK pathway components and occludin also were examined. Our results showed that microwave radiation caused intercellular tight junctions to broaden and fracture with decreased TEER values and increased HRP permeability. After microwave exposure, activation of the VEGF/Flk-1-ERK pathway and Tyr phosphorylation of occludin were observed, along with down-regulated expression and interaction of occludin with zonula occludens-1 (ZO-1). After Flk-1 (SU5416) and MEK1/2 (U0126) inhibitors were used, the structure and function of the BBB were recovered. The increase in expression of ERK signal transduction molecules was muted, while the expression and the activity of occludin were accelerated, as well as the interactions of occludin with p-ERK and ZO-1 following microwave radiation. Thus, microwave radiation may induce BBB damage by activating the VEGF/Flk-1-ERK pathway, enhancing Tyr phosphorylation of occludin, while partially inhibiting expression and interaction of occludin with ZO-1.

Anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given intramuscularly in animals.

PubMed

Hyun, J E; Li, D W; Lee, E B; Jeong, C S

2001-12-01

The evaluation of the anti-inflammatory, analgesic and antipyretic activities of loxoprofen sodium given in intramuscular route was investigated as compared to oral application in rats and mice. The intramuscular ED50 values of loxoprofen sodium in carrageenan edema and vascular permeability tests are 1.15 and 7.8 mg/kg, respectively, which represent more potent than in case of oral application. Its therapeutic effects in adjuvant arthritis were shown at 6 mg/kg i.m. and 3mg/kg p.o. Analgesic effect was shown to be more potent as given intramuscularly. Similar potency of antipyretic effects was shown in both administration routes. Considerably weak gastric damages were observed in intramuscular application.

The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae)

PubMed Central

Deeds, Jonathan R.; Hoesch, Robert E.; Place, Allen R.; Kao, Joseph P.Y.

2015-01-01

This study demonstrates that the polyketide toxin karlotoxin 2 (KmTx 2) produced by Karlodinium veneficum, a dinoflagellate associated with fish kills in temperate estuaries worldwide, alters vertebrate cell membrane permeability. Microfluorimetric and electrophysiological measurements were used to determine that vertebrate cellular toxicity occurs through non-selective permeabilization of plasma membranes, leading to osmotic cell lysis. Previous studies showed that KmTx 2 is lethal to fish at naturally-occurring concentrations measured during fish kills, while sub-lethal doses severely damage gill epithelia. This study provides a mechanistic explanation for the association between K. veneficum blooms and fish kills that has long been observed in temperate estuaries worldwide. PMID:25546005

The Possible Role of Tumor Necrosis Factor-α in Diabetic Polyneuropathy

PubMed Central

Yagihashi, Soroku; Toyota, Takayoshi

2003-01-01

In this review, the authors provide evidences that imply the role of tumor necrosis factor-α (TNF-α) in the pathogenesis of diabetic complications, especially diabetic polyneuropathy. Under chronic hyperglycemia, endogenous TNF-α production is accelerated in microvascular and neural tissues, which may undergo an increased microvascular permeability, hypercoagulability, and nerve damage, thus initiating and promoting the development of characteristic lesions of diabetic microangiopathy and polyneuropathy. Enhanced TNF-α production may also promote atherosclerosis due to increased insulin resistance and the expression of adhesion molecules. Clinical application of specific agents that suppress production and/or activity of TNF-α may inhibit the development and exacerbation of chronic diabetic complications. PMID:14630568

2-Methylcitric acid impairs glutamate metabolism and induces permeability transition in brain mitochondria.

PubMed

Amaral, Alexandre Umpierrez; Cecatto, Cristiane; Castilho, Roger Frigério; Wajner, Moacir

2016-04-01

Accumulation of 2-methylcitric acid (2MCA) is observed in methylmalonic and propionic acidemias, which are clinically characterized by severe neurological symptoms. The exact pathogenetic mechanisms of brain abnormalities in these diseases are poorly established and very little has been reported on the role of 2MCA. In the present work we found that 2MCA markedly inhibited ADP-stimulated and uncoupled respiration in mitochondria supported by glutamate, with a less significant inhibition in pyruvate plus malate respiring mitochondria. However, no alterations occurred when α-ketoglutarate or succinate was used as respiratory substrates, suggesting a defect on glutamate oxidative metabolism. It was also observed that 2MCA decreased ATP formation in glutamate plus malate or pyruvate plus malate-supported mitochondria. Furthermore, 2MCA inhibited glutamate dehydrogenase activity at concentrations as low as 0.5 mM. Kinetic studies revealed that this inhibitory effect was competitive in relation to glutamate. In contrast, assays of osmotic swelling in non-respiring mitochondria suggested that 2MCA did not significantly impair mitochondrial glutamate transport. Finally, 2MCA provoked a significant decrease in mitochondrial membrane potential and induced swelling in Ca(2+)-loaded mitochondria supported by different substrates. These effects were totally prevented by cyclosporine A plus ADP or ruthenium red, indicating induction of mitochondrial permeability transition. Taken together, our data strongly indicate that 2MCA behaves as a potent inhibitor of glutamate oxidation by inhibiting glutamate dehydrogenase activity and as a permeability transition inducer, disturbing mitochondrial energy homeostasis. We presume that 2MCA-induced mitochondrial deleterious effects may contribute to the pathogenesis of brain damage in patients affected by methylmalonic and propionic acidemias. We propose that brain glutamate oxidation is disturbed by 2-methylcitric acid (2MCA), which accumulates in tissues from patients with propionic and methylmalonic acidemias because of a competitive inhibition of glutamate dehydrogenase (GDH) activity. 2MCA also induced mitochondrial permeability transition (PT) and decreased ATP generation in brain mitochondria. We believe that these pathomechanisms may be involved in the neurological dysfunction of these diseases. © 2016 International Society for Neurochemistry.

Porosity, permeability and 3D fracture network characterisation of dolomite reservoir rock samples

PubMed Central

Voorn, Maarten; Exner, Ulrike; Barnhoorn, Auke; Baud, Patrick; Reuschlé, Thierry

2015-01-01

With fractured rocks making up an important part of hydrocarbon reservoirs worldwide, detailed analysis of fractures and fracture networks is essential. However, common analyses on drill core and plug samples taken from such reservoirs (including hand specimen analysis, thin section analysis and laboratory porosity and permeability determination) however suffer from various problems, such as having a limited resolution, providing only 2D and no internal structure information, being destructive on the samples and/or not being representative for full fracture networks. In this paper, we therefore explore the use of an additional method – non-destructive 3D X-ray micro-Computed Tomography (μCT) – to obtain more information on such fractured samples. Seven plug-sized samples were selected from narrowly fractured rocks of the Hauptdolomit formation, taken from wellbores in the Vienna basin, Austria. These samples span a range of different fault rocks in a fault zone interpretation, from damage zone to fault core. We process the 3D μCT data in this study by a Hessian-based fracture filtering routine and can successfully extract porosity, fracture aperture, fracture density and fracture orientations – in bulk as well as locally. Additionally, thin sections made from selected plug samples provide 2D information with a much higher detail than the μCT data. Finally, gas- and water permeability measurements under confining pressure provide an important link (at least in order of magnitude) towards more realistic reservoir conditions. This study shows that 3D μCT can be applied efficiently on plug-sized samples of naturally fractured rocks, and that although there are limitations, several important parameters can be extracted. μCT can therefore be a useful addition to studies on such reservoir rocks, and provide valuable input for modelling and simulations. Also permeability experiments under confining pressure provide important additional insights. Combining these and other methods can therefore be a powerful approach in microstructural analysis of reservoir rocks, especially when applying the concepts that we present (on a small set of samples) in a larger study, in an automated and standardised manner. PMID:26549935

Porosity, permeability and 3D fracture network characterisation of dolomite reservoir rock samples.

PubMed

Voorn, Maarten; Exner, Ulrike; Barnhoorn, Auke; Baud, Patrick; Reuschlé, Thierry

2015-03-01

With fractured rocks making up an important part of hydrocarbon reservoirs worldwide, detailed analysis of fractures and fracture networks is essential. However, common analyses on drill core and plug samples taken from such reservoirs (including hand specimen analysis, thin section analysis and laboratory porosity and permeability determination) however suffer from various problems, such as having a limited resolution, providing only 2D and no internal structure information, being destructive on the samples and/or not being representative for full fracture networks. In this paper, we therefore explore the use of an additional method - non-destructive 3D X-ray micro-Computed Tomography (μCT) - to obtain more information on such fractured samples. Seven plug-sized samples were selected from narrowly fractured rocks of the Hauptdolomit formation, taken from wellbores in the Vienna basin, Austria. These samples span a range of different fault rocks in a fault zone interpretation, from damage zone to fault core. We process the 3D μCT data in this study by a Hessian-based fracture filtering routine and can successfully extract porosity, fracture aperture, fracture density and fracture orientations - in bulk as well as locally. Additionally, thin sections made from selected plug samples provide 2D information with a much higher detail than the μCT data. Finally, gas- and water permeability measurements under confining pressure provide an important link (at least in order of magnitude) towards more realistic reservoir conditions. This study shows that 3D μCT can be applied efficiently on plug-sized samples of naturally fractured rocks, and that although there are limitations, several important parameters can be extracted. μCT can therefore be a useful addition to studies on such reservoir rocks, and provide valuable input for modelling and simulations. Also permeability experiments under confining pressure provide important additional insights. Combining these and other methods can therefore be a powerful approach in microstructural analysis of reservoir rocks, especially when applying the concepts that we present (on a small set of samples) in a larger study, in an automated and standardised manner.

The Northwest Geysers EGS Demonstration Project, California – Part 2: Modeling and interpretation

DOE PAGES

Rutqvist, Jonny; Jeanne, Pierre; Dobson, Patrick F.; ...

2015-09-02

In this paper, we summarize the results of coupled thermal, hydraulic, and mechanical (THM) modeling in support of the Northwest Geysers EGS Demonstration Project, which aims at enhancing production from a known High Temperature Reservoir (HTR) (280–400 °C) located under the conventional (240 °C) geothermal steam reservoir. The THM modeling was conducted to investigate geomechanical effects of cold-water injection during the stimulation of the EGS, first to predict the extent of the stimulation zone for a given injection schedule, and then to conduct interpretive analyses of the actual stimulation. By using a calibrated THM model based on historic injection and microseismic datamore » at a nearby well, we could reasonably predict the extent of the stimulation zone around the injection well, at least for the first few months of injection. However, observed microseismic evolution and pressure responses over the one-year stimulation-injection revealed more heterogeneous behavior as a result of more complex geology, including a network of shear zones. Therefore, for an interpretive analysis of the one-year stimulation campaign, we included two sets of vertical shear zones within the model; a set of more permeable NW-striking shear zones and a set of less permeable NE-striking shear zones. Our modeling indicates that the microseismic events in this system are related to shear reactivation of pre-existing fractures, triggered by the combined effects of injection-induced cooling around the injection well and rapid (but small) changes in steam pressure as far as a kilometer from the injection well. Overall, the integrated monitoring and modeling of microseismicity, ground surface deformations, reservoir pressure, fluid chemical composition, and seismic tomography depict an EGS system hydraulically bounded by some of the NE-striking low permeability shear zones, with the more permeable NW-striking shear zone providing liquid flow paths for stimulation deep (several kilometers) down into the HTR. The mo deling indicates that a significant mechanical degradation (damage) inferred from seismic tomography, and potential changes in fracture porosity inferred from cross-well pressure responses, are related to shear rupture in the stimulation zone driven by both pressure and cooling effects.« less

The Northwest Geysers EGS Demonstration Project, California – Part 2: Modeling and interpretation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rutqvist, Jonny; Jeanne, Pierre; Dobson, Patrick F.

In this paper, we summarize the results of coupled thermal, hydraulic, and mechanical (THM) modeling in support of the Northwest Geysers EGS Demonstration Project, which aims at enhancing production from a known High Temperature Reservoir (HTR) (280–400 °C) located under the conventional (240 °C) geothermal steam reservoir. The THM modeling was conducted to investigate geomechanical effects of cold-water injection during the stimulation of the EGS, first to predict the extent of the stimulation zone for a given injection schedule, and then to conduct interpretive analyses of the actual stimulation. By using a calibrated THM model based on historic injection and microseismic datamore » at a nearby well, we could reasonably predict the extent of the stimulation zone around the injection well, at least for the first few months of injection. However, observed microseismic evolution and pressure responses over the one-year stimulation-injection revealed more heterogeneous behavior as a result of more complex geology, including a network of shear zones. Therefore, for an interpretive analysis of the one-year stimulation campaign, we included two sets of vertical shear zones within the model; a set of more permeable NW-striking shear zones and a set of less permeable NE-striking shear zones. Our modeling indicates that the microseismic events in this system are related to shear reactivation of pre-existing fractures, triggered by the combined effects of injection-induced cooling around the injection well and rapid (but small) changes in steam pressure as far as a kilometer from the injection well. Overall, the integrated monitoring and modeling of microseismicity, ground surface deformations, reservoir pressure, fluid chemical composition, and seismic tomography depict an EGS system hydraulically bounded by some of the NE-striking low permeability shear zones, with the more permeable NW-striking shear zone providing liquid flow paths for stimulation deep (several kilometers) down into the HTR. The mo deling indicates that a significant mechanical degradation (damage) inferred from seismic tomography, and potential changes in fracture porosity inferred from cross-well pressure responses, are related to shear rupture in the stimulation zone driven by both pressure and cooling effects.« less

Integrated approach for quantification of fractured tight reservoir rocks: Porosity, permeability analyses and 3D fracture network characterisation on fractured dolomite samples

NASA Astrophysics Data System (ADS)

Voorn, Maarten; Barnhoorn, Auke; Exner, Ulrike; Baud, Patrick; Reuschlé, Thierry

2015-04-01

Fractured reservoir rocks make up an important part of the hydrocarbon reservoirs worldwide. A detailed analysis of fractures and fracture networks in reservoir rock samples is thus essential to determine the potential of these fractured reservoirs. However, common analyses on drill core and plug samples taken from such reservoirs (including hand specimen analysis, thin section analysis and laboratory porosity and permeability determination) suffer from various problems, such as having a limited resolution, providing only 2D and no internal structure information, being destructive on the samples and/or not being representative for full fracture networks. In this study, we therefore explore the use of an additional method - non-destructive 3D X-ray micro-Computed Tomography (μCT) - to obtain more information on such fractured samples. Seven plug-sized samples were selected from narrowly fractured rocks of the Hauptdolomit formation, taken from wellbores in the Vienna Basin, Austria. These samples span a range of different fault rocks in a fault zone interpretation, from damage zone to fault core. 3D μCT data is used to extract porosity, fracture aperture, fracture density and fracture orientations - in bulk as well as locally. The 3D analyses are complemented with thin sections made to provide some 2D information with a much higher detail than the μCT data. Finally, gas- and water permeability measurements under confining pressure provide an important link (at least in order of magnitude) of the µCT results towards more realistic reservoir conditions. Our results show that 3D μCT can be applied efficiently on plug-sized samples of naturally fractured rocks, and that several important parameters can be extracted. μCT can therefore be a useful addition to studies on such reservoir rocks, and provide valuable input for modelling and simulations. Also permeability experiments under confining pressure provide important additional insights. Combining these and other methods can therefore be a powerful approach in microstructural analysis of reservoir rocks, especially when applying the concepts that we present (on a small set of samples) in a larger study, in an automated and standardised manner.

Exercise potentiation of lung injury following inhalation of a pneumoedematogenic gas: perfluoroisobutylene.

PubMed

Lehnert, B E; Archuleta, D; Gurley, L R; Session, W; Behr, M J; Lehnert, N M; Stavert, D M

1995-01-01

Exercise performed after exposure to various pneumoedematogenic gases can increase the severity of pulmonary edema beyond that which occurs when exposure is followed by rest. The present study was performed to investigate the potential relationship between a preexisting breach in the lung's permeability status following exposure to an edematogenic gas (perfluoroisobutylene, PFIB) and the potentiating effects of postexposure exercise. Rats were exposed to a concentration of PFIB (100 mg/M3 for 10 min) that results in a unique postexposure latency period (approximately 8 h) prior to the occurrence of overt pulmonary edema. The study examined how exercise performed during and after the latency period affects the severity of the injurious response to this toxic gas. The initial results indicated that exercise performed during the post-PFIB exposure latency period does not potentiate the injurious response, as judged by conventional lung gravimetric and histopathological criteria, but when overt pulmonary edema was preexistent, exercise had a potentiating effect. Changes in lavageable protein were assessed as a more sensitive indicator of permeability changes that may occur during the latency period following PFIB exposure, and the study examined how exercise performed early during the latency period affects this index of pulmonary edema. The study also assessed whether PFIB-induced damage to lung cells is enhanced by exercise during the latency period by measuring lavageable lactate dehydrogenase activity. The results from these latter experiments suggest that a preexisting enhancement in lung permeability is not an absolute requirement for exercise to potentiate the pulmonary edematous response in lungs that are undergoing insidious injury, and that postexposure exercise does not enhance the cell-killing effects of PFIB as a mechanism underlying the exercise potentiating response. Conceivably, the ability of exercise to increase lavageable protein in the absence of a preexisting increase in lung permeability may be due to hyperventilation- and/or pulmonary hypertension-associated intercellular junctional changes that may occur during exercise. Additionally, it remains possible that exercise during PFIB-induced insideous lung injury results in an enhancement in the rate of transcellular transport of blood proteins onto the alveolar surface.

Structural and geochemical characteristics of faulted sediments and inferences on the role of water in deformatiion, Rio Grande Rift, New Mexico

USGS Publications Warehouse

Caine, Jonathan S.; Minor, S.A.

2009-01-01

The San Ysidro fault is a spectacularly exposed normal fault located in the northwestern Albuquerque Basin of the Rio Grande Rift. This intrabasin fault is representative of many faults that formed in poorly lithified sediments throughout the rift. The fault is exposed over nearly 10 km and accommodates nearly 700 m of dip slip in subhorizontal, siliciclastic sediments. The extent of the exposure facilitates study of along-strike variations in deformation mechanisms, archi tecture, geochemistry, and permeability. The fault is composed of structural and hydrogeologic components that include a clay-rich fault core, a calcite-cemented mixed zone, and a poorly developed damage zone primarily consisting of deformation bands. Structural textures suggest that initial deformation in the fault occurred at low temperature and pressure, was within the paleosaturated zone of the evolving Rio Grande Rift, and was dominated by particulate flow. Little geochemical change is apparent across the fault zone other than due to secondary processes. The lack of fault-related geochemical change is interpreted to reflect the fundamental nature of water-saturated, particulate fl ow. Early mechanical entrainment of low-permeability clays into the fault core likely caused damming of groundwater flow on the up-gradient, footwall side of the fault. This may have caused a pressure gradient and flow of calcite-saturated waters in higher-permeability, fault-entrained siliciclastic sediments, ultimately promoting their cementation by sparry calcite. Once developed, the cemented and clay-rich fault has likely been, and continues to be, a partial barrier to cross-fault groundwater flow, as suggested by petrophysical measurements. Aeromagnetic data indicate that there may be many more unmapped faults with similar lengths to the San Ysidro fault buried within Rio Grande basins. If these buried faults formed by the same processes that formed the San Ysidro fault and have persistent low-permeability cores and cemented mixed zones, they could compartmentalize the basin-fill aquifers more than is currently realized, particularly if pumping stresses continue to increase in response to population growth. ?? 2009 Geological Society of America.

Evaluation of permeability alteration and epithelial-mesenchymal transition induced by transforming growth factor-β1 in A549, NCI-H441, and Calu-3 cells: Development of an in vitro model of respiratory epithelial cells in idiopathic pulmonary fibrosis.

PubMed

Togami, Kohei; Yamaguchi, Kotaro; Chono, Sumio; Tada, Hitoshi

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease, which is accompanied by changes in lung structure. With regard to treatment, aerosolized drugs administered intrapulmonarily are rapidly distributed into the plasma and do not remain in the lungs due to damage to the alveolar epithelium that occurs from pulmonary fibrosis. In this study, we sought to develop an in vitro model of respiratory epithelial cells in IPF for the evaluation of the intrapulmonary distribution of aerosolized drugs. We investigated transforming growth factor (TGF)-β 1 -induced epithelial-mesenchymal transition (EMT) and permeability alteration in A549, NCI-H441, and Calu-3 cell monolayers. After TGF-β 1 treatment of A549, NCI-H441, and Calu-3 cells, EMT markers including E-cadherin and vimentin and tight junction proteins including claudins-1, -3, and -5 were stained using immunofluorescence methods and detected using immunoblotting methods. Transport experiments were performed using TGF-β 1 -treated cell monolayers and fluorescein isothiocyanate dextrans (FD; 4.4, 10, and 70kDa). In addition, TGF-β 1 -induced apoptosis and necrosis were evaluated by flow cytometry using Annexin V and ethidium homodimer III, respectively. In NCI-H441 cells, incomplete EMT, destruction of claudins-1 and -3, and enhancement of FD permeability were caused by TGF-β 1 treatment. In A549 cells, complete EMT occurred but was not adequate for transport experiments because of low transepithelial electrical resistance. Whereas in Calu-3 cells, no changes were observed. TGF-β 1 -induced apoptosis and necrosis were not observed in any of the cell lines. Incomplete EMT and permeability enhancement were observed in the alveolar epithelium of IPF. Therefore, our results indicate that TGF-β 1 -treated NCI-H441 cell monolayers may serve as a useful in vitro model of respiratory epithelial cells for IPF. Copyright © 2017 Elsevier Inc. All rights reserved.

Optical clearing of skin using flash lamp-induced enhancement of epidermal permeability.

PubMed

Tuchin, V V; Altshuler, G B; Gavrilova, A A; Pravdin, A B; Tabatadze, D; Childs, J; Yaroslavsky, I V

2006-10-01

Strong light scattering in skin prevents precise targeting of optical energy in therapeutic and diagnostic applications. Optical immersion based on matching refractive index of scattering centers with that of surrounding matter through introduction of an exogenous index-matching agent can alleviate the problem. However, slow diffusion of the index-matching agent through skin barrier makes practical implementation of this approach difficult. We propose a method of accelerating penetration of the index-matching compounds by enhancing skin permeability through creating a lattice of micro-zones (islets) of limited thermal damage in the stratum corneum (SC). A flash lamp (intense pulsed light) system and an island mask with a pattern of absorbing centers (center size approximately 75-120 microm, lattice pitch approximately 450-500 microm) were used to create the lattice of islets of damage (LID). Index-matching agents, such as glucose solution, propylene glycol solution, and glycerol solution, were applied. Experimental results of optical clearing ex vivo rat and pig skin, and ex vivo and in vivo human skin are presented. Optical transmission spectra of the skin samples with LID were measured during some 2 hours after application of index-matching chemical agents. In order to assess and compare the clearing rate under different treatment and clearing agents we calculated the quantity that we call "relative transmittance": T(rel) = I(t)(lambda)/I(0)(lambda), were I(t)(lambda) is the intensity measured at elapsed time t. The dynamics of relative transmittance of skin samples at 470 and 650 nm shows that the implementation of limited thermal damage technique leads to a 3-10-fold increase of optical clearing (rise of transmittance) rate compared to the results obtained when the samples were treated with high-intensity light pulses but without the use of island damage mask (IDM). It was observed from the plotted spectra of relative transmittance that the maximum increase of transmitted light intensity has been obtained with glucose solution as a clearing agent. Noteworthy is the difference in the trend of spectral curves: relative transmittance spectrum for glycerol reveals, on the whole, a greater slope which may be indicative of higher extent of index matching between the scattering centers and base material for this index-matching agent. Under the transillumination of the skin sample by the wide flat beam the more effective clearing (the increase of transmitted intensity) is attained within the hemoglobin absorption bands; with the narrow quasi-collimated beam the higher relative transmittance was observed over the intervals of minimum absorption. The use of specially designed island mask combined with non-laser intensive pulse irradiation produces a lattice of islands of limited thermal damage in SC that substantially enhances the penetration rate of topically applied index-matching agents. The suggested technique gave comparable magnitudes of clearing dynamics enhancement for glucose solution, glycerol solution, and propylene glycol solution applied to mammalian skin.

Ascorbate and low concentrations of FeSO4 induce Ca2+-dependent pore in rat liver mitochondria.

PubMed

Brailovskaya, I V; Starkov, A A; Mokhova, E N

2001-08-01

Oxidative stress is one of the most frequent causes of tissue and cell injury in various pathologies. The molecular mechanism of mitochondrial damage under conditions of oxidative stress induced in vitro with low concentrations of FeSO4 and ascorbate (vitamin C) was studied. FeSO4 (1-4 microM) added to rat liver mitochondria that were incubated in the presence of 2.3 mM ascorbate induced (with a certain delay) a decrease in membrane potential and high-amplitude swelling. It also significantly decreased the ability of mitochondria to accumulate exogenous Ca2+. All the effects of FeSO4 + ascorbate were essentially prevented by cyclosporin A, a specific inhibitor of the mitochondrial Ca2+-dependent pore (also known as the mitochondrial permeability transition). EGTA restored the membrane potential of mitochondria de-energized with FeSO4 + ascorbate. We hypothesize that oxidative stress induced in vitro with FeSO4 and millimolar concentrations of ascorbate damages mitochondria by inducing the cyclosporin A-sensitive Ca2+-dependent pore in the inner mitochondrial membrane.

Octanal inhibits spore germination of Penicillium digitatum involving membrane peroxidation.

PubMed

Dou, Shiwen; Liu, Shengquan; Xu, Xiaoyong; OuYang, Qiuli; Tao, Nengguo

2017-07-01

Octanal is a potential alternative to chemical fungicides in controlling postharvest disease of citrus fruit. In this study, the antifungal activity and the underlying mechanism of octanal against spore germination of Penicillium digitatum, one of the main postharvest pathogens in citrus, were investigated. Results showed that octanal at different concentrations (0, 0.25, 0.50, 1.00, 2.00 μl/ml) inhibited the growth of P. digitatum spores in a dose-dependent manner. The morphology and the membrane permeability of P. digitatum spores were visibly altered by 0.25 and 2.00 μl/ml of octanal. Meanwhile, octanal decreased the total lipids contents of P. digitatum spores, indicating that the membrane integrity is damaged. Furthermore, octanal apparently induced the massive accumulation of total malonaldehyde (MDA) and the reactive oxygen species (ROS). An increase in the activities of lipoxygenase (LOX), NADH oxidase, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) was also observed. These results suggested that a membrane damage mechanism involving membrane peroxidation might contribute to the antifungal activity of octanal against P. digitatum spores.

Deep particle bed dryout model based on flooding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuan, P.

1987-01-01

Examination of the damaged Three Mile island Unit 2 (TMI-2) reactor indicates that a deep (approx. 1-m) bed of relatively large (approx. 1-mm) particles was formed in the core. Cooling of such beds is crucial to the arrest of core damage progression. The Lipinski model, based on flows in the bed, has been used to predict the coolability, but uncertainties exist in the turbulent permeability. Models based on flooding at the top of the bed either have a dimensional viscosity term, or no viscosity dependence, thus limiting their applicability. This paper presents a dimensionless correlation based on flooding data thatmore » involves a liquid Reynolds number. The derived dryout model from this correlation is compared with data for deep beds of large particles at atmospheric pressure, and with other models over a wide pressure range. It is concluded that the present model can give quite accurate predictions for the dryout heat flux of particle beds formed during a light water reactor accident and it is easy to use and agrees with the Lipinski n = 5 model, which requires iterative calculations.« less

Folded fabric tunes rock deformation and failure mode in the upper crust.

PubMed

Agliardi, F; Dobbs, M R; Zanchetta, S; Vinciguerra, S

2017-11-10

The micro-mechanisms of brittle failure affect the bulk mechanical behaviour and permeability of crustal rocks. In low-porosity crystalline rocks, these mechanisms are related to mineralogy and fabric anisotropy, while confining pressure, temperature and strain rates regulate the transition from brittle to ductile behaviour. However, the effects of folded anisotropic fabrics, widespread in orogenic settings, on the mechanical behaviour of crustal rocks are largely unknown. Here we explore the deformation and failure behaviour of a representative folded gneiss, by combining the results of triaxial deformation experiments carried out while monitoring microseismicity with microstructural and damage proxies analyses. We show that folded crystalline rocks in upper crustal conditions exhibit dramatic strength heterogeneity and contrasting failure modes at identical confining pressure and room temperature, depending on the geometrical relationships between stress and two different anisotropies associated to the folded rock fabric. These anisotropies modulate the competition among quartz- and mica-dominated microscopic damage processes, resulting in transitional brittle to semi-brittle modes under P and T much lower than expected. This has significant implications on scales relevant to seismicity, energy resources, engineering applications and geohazards.

Anomalous aging of EPDM and FEPM under combined thermo-oxidative and hydrolytic conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redline, Erica M.; Celina, Mathias C.; Harris, Charles E.

Previous observation of EPDM and FEPM materials aged in thermo-oxidative and thermo-oxidative plus hydrolytic environments revealed an unusual trend: the degradation and disintegration of these polymers in the former case but the ability to maintain mechanical performance and shape in the latter. No abnormalities were observed in the chemical (oxidation rates, FTIR spectra, solvent uptake, gel content, and weight loss vs. temperature) or physical (modulus profile) measurements that could explain these empirically observed aging differences. A second controlled aging test was conducted to verify this trend using only EPDM. Once again it was shown that thermo-oxidative conditions appear to causemore » more degradative damage (enhanced embrittlement) than observed for the combined thermo-oxidative plus hydrolytic environments. From these data we conclude that water may favorably interfere with normal thermo-oxidative degradation processes. This interference may occur via some combination of chemical and physical property changes in the presence of steam such as: oxidation rate and O 2 permeability changes, additional sensitivity to hydrolytic damage, and/or mechanistic changes in relation to pH and hydroperoxide formation.« less

Anomalous aging of EPDM and FEPM under combined thermo-oxidative and hydrolytic conditions

DOE PAGES

Redline, Erica M.; Celina, Mathias C.; Harris, Charles E.; ...

2017-09-15

Previous observation of EPDM and FEPM materials aged in thermo-oxidative and thermo-oxidative plus hydrolytic environments revealed an unusual trend: the degradation and disintegration of these polymers in the former case but the ability to maintain mechanical performance and shape in the latter. No abnormalities were observed in the chemical (oxidation rates, FTIR spectra, solvent uptake, gel content, and weight loss vs. temperature) or physical (modulus profile) measurements that could explain these empirically observed aging differences. A second controlled aging test was conducted to verify this trend using only EPDM. Once again it was shown that thermo-oxidative conditions appear to causemore » more degradative damage (enhanced embrittlement) than observed for the combined thermo-oxidative plus hydrolytic environments. From these data we conclude that water may favorably interfere with normal thermo-oxidative degradation processes. This interference may occur via some combination of chemical and physical property changes in the presence of steam such as: oxidation rate and O 2 permeability changes, additional sensitivity to hydrolytic damage, and/or mechanistic changes in relation to pH and hydroperoxide formation.« less

Arachidonic acid with taurine enhances pulmonary absorption of macromolecules without any serious histopathological damages.

PubMed

Miyake, Masateru; Minami, Takanori; Yamazaki, Hiroyuki; Emoto, Chie; Mukai, Tadashi; Toguchi, Hajime

2017-05-01

Therapeutic peptides and protein are being used in several indications; however, their poor permeability still remains to be solved. This study focused on the pulmonary route of macromolecules. First, the effects of arachidonic acid (AA) as an absorption enhancer on drug serum concentration, after intratracheal administration, were investigated in rats. Second, the safety of AA was assessed in rats in an acute toxicity study for 7days. AA enhanced the exposure of both interferon-α (IFN-α) and fluorescein isothiocyanate 4000 (FD-4). In addition, the histopathological analysis indicated that AA caused alveolitis and bronchitis in rats. In combination with Taurine (Tau), these lung injuries were prevented through the histopathological analysis. The combined use of Tau with AA did not show any changes in the pharmacokinetics of FD-4. From these results, we suggest the combined use of AA with Tau as a novel formulation on the pulmonary route of macromolecule drugs. This formulation could improve the bioavailability of macromolecule drugs without any serious local damage to the lungs. Copyright © 2017 Elsevier B.V. All rights reserved.

Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse.

PubMed

Liu, Qianying; Lei, Zhixin; Guo, Jingchao; Liu, Aimei; Lu, Qirong; Fatima, Zainab; Khaliq, Haseeb; Shabbir, Muhammad A B; Maan, Muhammad Kashif; Wu, Qinghua; Dai, Menghong; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

2018-01-01

Mequindox (MEQ), belonging to quinoxaline-di- N -oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo .

Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse

PubMed Central

Liu, Qianying; Lei, Zhixin; Guo, Jingchao; Liu, Aimei; Lu, Qirong; Fatima, Zainab; Khaliq, Haseeb; Shabbir, Muhammad A. B.; Maan, Muhammad Kashif; Wu, Qinghua; Dai, Menghong; Wang, Xu; Pan, Yuanhu; Yuan, Zonghui

2018-01-01

Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo. PMID:29765325

Antimicrobial effect and membrane-active mechanism of tea polyphenols against Serratia marcescens.

PubMed

Yi, Shumin; Wang, Wei; Bai, Fengling; Zhu, Junli; Li, Jianrong; Li, Xuepeng; Xu, Yongxia; Sun, Tong; He, Yutang

2014-02-01

In this study, we investigated the antimicrobial effect of tea polyphenols (TP) against Serratia marcescens and examined the related mechanism. Morphology changes of S. marcescens were first observed by transmission electron microscopy after treatment with TP, which indicated that the primary inhibition action of TP was to damage the bacterial cell membranes. The permeability of the outer and inner membrane of S. marcescens dramatically increased after TP treatment, which caused severe disruption of cell membrane, followed by the release of small cellular molecules. Furthermore, a proteomics approach based on two-dimensional gel electrophoresis and MALDI-TOF/TOF MS analysis was used to study the difference of membrane protein expression in the control and TP treatment S. marcescens. The results showed that the expression of some metabolism enzymes and chaperones in TP-treated S. marcescens significantly increased compared to the untreated group, which might result in the metabolic disorder of this bacteria. Taken together, our results first demonstrated that TP had a significant growth inhibition effect on S. marcescens through cell membrane damage.

Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio cholerae and Other Vibrio species.

PubMed

Acosta-Smith, Erika; Viveros-Jiménez, Karina; Canizalez-Román, Adrian; Reyes-Lopez, Magda; Bolscher, Jan G M; Nazmi, Kamran; Flores-Villaseñor, Hector; Alapizco-Castro, Gerardo; de la Garza, Mireya; Martínez-Garcia, Jesús J; Velazquez-Roman, Jorge; Leon-Sicairos, Nidia

2017-01-01

Vibrio is a genus of Gram-negative bacteria, some of which can cause serious infectious diseases. Vibrio infections are associated with the consumption of contaminated food and classified in Vibrio cholera infections and non-cholera Vibrio infections. In the present study, we investigate whether bovine lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences, are able to inhibit the growth or have bactericidal effect against V. cholerae and other Vibrio species. The antibacterial activity of LF and LF-peptides was assessed by kinetics of growth or determination of colony forming unit in bacteria treated with the peptides and antibiotics. To get insight in the mode of action, the interaction between bLF and bLF-peptides (coupled to FITC) and V. cholera was evaluated. The damage of effector-induced bacterial membrane permeability was measured by inclusion of the fluorescent dye propidium iodide using flow cytometry, whereas the bacterial ultrastructural damage in bacteria treated was observed by transmission electron microscopy. The results showed that bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera permeabilized the bacteria which membranes were seriously damaged. Assays with a multidrug-resistant strain of Vibrio species indicated that combination of sub-lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the concentration of the antibiotics to reach 95% growth inhibition. Furthermore, LFchimera were effective to inhibit the V. cholerae counts and damage due to this bacterium in a model mice. These data suggest that LFchimera and bLF are potential candidates to combat the V. cholerae and other multidrug resistant Vibrio species.

Numerical modeling of fluid flow in a fault zone: a case of study from Majella Mountain (Italy).

NASA Astrophysics Data System (ADS)

Romano, Valentina; Battaglia, Maurizio; Bigi, Sabina; De'Haven Hyman, Jeffrey; Valocchi, Albert J.

2017-04-01

The study of fluid flow in fractured rocks plays a key role in reservoir management, including CO2 sequestration and waste isolation. We present a numerical model of fluid flow in a fault zone, based on field data acquired in Majella Mountain, in the Central Apennines (Italy). This fault zone is considered a good analogue for the massive presence of fluid migration in the form of tar. Faults are mechanical features and cause permeability heterogeneities in the upper crust, so they strongly influence fluid flow. The distribution of the main components (core, damage zone) can lead the fault zone to act as a conduit, a barrier, or a combined conduit-barrier system. We integrated existing information and our own structural surveys of the area to better identify the major fault features (e.g., type of fractures, statistical properties, geometrical and petro-physical characteristics). In our model the damage zones of the fault are described as discretely fractured medium, while the core of the fault as a porous one. Our model utilizes the dfnWorks code, a parallelized computational suite, developed at Los Alamos National Laboratory (LANL), that generates three dimensional Discrete Fracture Network (DFN) of the damage zones of the fault and characterizes its hydraulic parameters. The challenge of the study is the coupling between the discrete domain of the damage zones and the continuum one of the core. The field investigations and the basic computational workflow will be described, along with preliminary results of fluid flow simulation at the scale of the fault.

Cell-Permeable Parkin Proteins Suppress Parkinson Disease-Associated Phenotypes in Cultured Cells and Animals

PubMed Central

Duong, Tam; Kim, Jaetaek; Ruley, H. Earl; Jo, Daewoong

2014-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder of complex etiology characterized by the selective loss of dopaminergic neurons, particularly in the substantia nigra. Parkin, a tightly regulated E3 ubiquitin ligase, promotes the survival of dopaminergic neurons in both PD and Parkinsonian syndromes induced by acute exposures to neurotoxic agents. The present study assessed the potential of cell-permeable parkin (CP-Parkin) as a neuroprotective agent. Cellular uptake and tissue penetration of recombinant, enzymatically active parkin was markedly enhanced by the addition of a hydrophobic macromolecule transduction domain (MTD). The resulting CP-Parkin proteins (HPM13 and PM10) suppressed dopaminergic neuronal toxicity in cells and mice exposed to 6-hydroxydopamine (6-OHDH) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These included enhanced survival and dopamine expression in cultured CATH.a and SH-SY5Y neuronal cells; and protection against MPTP-induced damage in mice, notably preservation of tyrosine hydroxylase-positive cells with enhanced dopamine expression in the striatum and midbrain, and preservation of gross motor function. These results demonstrate that CP-Parkin proteins can compensate for intrinsic limitations in the parkin response and provide a therapeutic strategy to augment parkin activity in vivo. PMID:25019626

MYB107 and MYB9 Homologs Regulate Suberin Deposition in Angiosperms

PubMed Central

Cohen, Hagai; Levy-Samocha, Dorit; Tzfadia, Oren; Panizel, Irina; Zeisler, Viktoria; Massalha, Hassan; Stern, Adi; Aharoni, Asaph

2016-01-01

Suberin, a polymer composed of both aliphatic and aromatic domains, is deposited as a rough matrix upon plant surface damage and during normal growth in the root endodermis, bark, specialized organs (e.g., potato [Solanum tuberosum] tubers), and seed coats. To identify genes associated with the developmental control of suberin deposition, we investigated the chemical composition and transcriptomes of suberized tomato (Solanum lycopersicum) and russet apple (Malus x domestica) fruit surfaces. Consequently, a gene expression signature for suberin polymer assembly was revealed that is highly conserved in angiosperms. Seed permeability assays of knockout mutants corresponding to signature genes revealed regulatory proteins (i.e., AtMYB9 and AtMYB107) required for suberin assembly in the Arabidopsis thaliana seed coat. Seeds of myb107 and myb9 Arabidopsis mutants displayed a significant reduction in suberin monomers and altered levels of other seed coat-associated metabolites. They also exhibited increased permeability, and lower germination capacities under osmotic and salt stress. AtMYB9 and AtMYB107 appear to synchronize the transcriptional induction of aliphatic and aromatic monomer biosynthesis and transport and suberin polymerization in the seed outer integument layer. Collectively, our findings establish a regulatory system controlling developmentally deposited suberin, which likely differs from the one of stress-induced polymer assembly recognized to date. PMID:27604696

Effects of CO 2 on mechanical variability and constitutive behavior of the Lower Tuscaloosa formation, Cranfield Injection Site, USA

DOE PAGES

Rinehart, Alex J.; Dewers, Thomas A.; Broome, Scott T.; ...

2016-08-25

We characterize geomechanical constitutive behavior of reservoir sandstones at conditions simulating the “Cranfield” Southeast Regional Carbon Sequestration Partnership injection program. From two cores of Lower Tuscaloosa Formation, three sandstone lithofacies were identified for mechanical testing based on permeability and lithology. These include: chlorite-cemented conglomeratic sandstone (Facies A); quartz-cemented fine sandstone (Facies B); and quartz- and calcite-cemented very fine sandstone (Facies C). We performed a suite of compression tests for each lithofacies at 100 °C and pore pressure of 30 MPa, including hydrostatic compression and triaxial tests at several confining pressures. Plugs were saturated with supercritical CO 2-saturated brine. Chemical environmentmore » affected the mechanical response of all three lithofacies, which experience initial plastic yielding at stresses far below estimated in situ stress. Measured elastic moduli degradation defines a secondary yield surface coinciding with in situ stress for Facies B and C. Facies A shows measurable volumetric creep strain and a failure envelope below estimates of in situ stress, linked to damage of chlorite cements by acidic pore solutions. Furthermore, the substantial weakening of a particular lithofacies by CO 2 demonstrates a possible chemical-mechanical coupling during injection at Cranfield with implications for CO 2 injection, reservoir permeability stimulation, and enhanced oil recovery.« less

Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. Roles in cell injury processes of pancreatitis.

PubMed

Gukovskaya, Anna S; Gukovsky, Ilya; Jung, Yoon; Mouria, Michelle; Pandol, Stephen J

2002-06-21

Apoptosis and necrosis are critical parameters of pancreatitis, the mechanisms of which remain unknown. Many characteristics of pancreatitis can be studied in vitro in pancreatic acini treated with high doses of cholecystokinin (CCK). We show here that CCK stimulates apoptosis and death signaling pathways in rat pancreatic acinar cells, including caspase activation, cytochrome c release, and mitochondrial depolarization. The mitochondrial dysfunction is mediated by upstream caspases (possibly caspase-8) and, in turn, leads to activation of caspase-3. CCK causes mitochondrial alterations through both permeability transition pore-dependent (cytochrome c release) and permeability transition pore-independent (mitochondrial depolarization) mechanisms. Caspase activation and mitochondrial alterations also occur in untreated pancreatic acinar cells; however, the underlying mechanisms are different. In particular, caspases protect untreated acinar cells from mitochondrial damage. We found that caspases not only mediate apoptosis but also regulate other parameters of CCK-induced acinar cell injury that are characteristic of pancreatitis; in particular, caspases negatively regulate necrosis and trypsin activation in acinar cells. The results suggest that the observed signaling pathways regulate parenchymal cell injury and death in CCK-induced pancreatitis. Protection against necrosis and trypsin activation by caspases can explain why the severity of pancreatitis in experimental models correlates inversely with the extent of apoptosis.

A Simplified Model for Multiphase Leakage through Faults with Applications for CO2 Storage

NASA Astrophysics Data System (ADS)

Watson, F. E.; Doster, F.

2017-12-01

In the context of geological CO2 storage, faults in the subsurface could affect storage security by acting as high permeability pathways which allow CO2 to flow upwards and away from the storage formation. To assess the likelihood of leakage through faults and the impacts faults might have on storage security numerical models are required. However, faults are complex geological features, usually consisting of a fault core surrounded by a highly fractured damage zone. A direct representation of these in a numerical model would require very fine grid resolution and would be computationally expensive. Here, we present the development of a reduced complexity model for fault flow using the vertically integrated formulation. This model captures the main features of the flow but does not require us to resolve the vertical dimension, nor the fault in the horizontal dimension, explicitly. It is thus less computationally expensive than full resolution models. Consequently, we can quickly model many realisations for parameter uncertainty studies of CO2 injection into faulted reservoirs. We develop the model based on explicitly simulating local 3D representations of faults for characteristic scenarios using the Matlab Reservoir Simulation Toolbox (MRST). We have assessed the impact of variables such as fault geometry, porosity and permeability on multiphase leakage rates.

Mitochondrial permeability transition in cardiac ischemia–reperfusion: whether cyclophilin D is a viable target for cardioprotection?

PubMed Central

Jang, Sehwan; Parodi-Rullan, Rebecca; Khuchua, Zaza; Kuznetsov, Andrey V.

2018-01-01

Growing number of studies provide strong evidence that the mitochondrial permeability transition pore (PTP), a non-selective channel in the inner mitochondrial membrane, is involved in the pathogenesis of cardiac ischemia–reperfusion and can be targeted to attenuate reperfusion-induced damage to the myocardium. The molecular identity of the PTP remains unknown and cyclophilin D is the only protein commonly accepted as a major regulator of the PTP opening. Therefore, cyclophilin D is an attractive target for pharmacological or genetic therapies to reduce ischemia–reperfusion injury in various animal models and humans. Most animal studies demonstrated cardioprotective effects of PTP inhibition; however, a recent large clinical trial conducted by international groups demonstrated that cyclosporine A, a cyclophilin D inhibitor, failed to protect the heart in patients with myocardial infarction. These studies, among others, raise the question of whether cyclophilin D, which plays an important physiological role in the regulation of cell metabolism and mitochondrial bioenergetics, is a viable target for cardioprotection. This review discusses previous studies to provide comprehensive information on the physiological role of cyclophilin D as well as PTP opening in the cell that can be taken into consideration for the development of new PTP inhibitors. PMID:28378042

Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

PubMed Central

Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S

2016-01-01

Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin.

PubMed

Araújo, Raquel Silva; Silveira, Ana Letícia Malheiros; de Sales E Souza, Éricka Lorenna; Freire, Rachel Horta; de Souza, Cristina Maria; Reis, Diego Carlos; Costa, Bruno Rocha Cordeiro; Sugimoto, Michelle Amantéa; Silveira, Josianne Nicácio; Dos Santos Martins, Flaviano; Cassali, Geovanni Dantas; Leite, Jacqueline Isaura Alvarez; Sousa, Lirlândia Pires; Ferreira, Adaliene Versiani Matos; Oliveira, Mônica Cristina; Cardoso, Valbert Nascimento

2017-08-30

Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use. Copyright © 2017. Published by Elsevier B.V.

Tauroursodeoxycholic acid inhibits endoplasmic reticulum stress, blocks mitochondrial permeability transition pore opening, and suppresses reperfusion injury through GSK-3ß in cardiac H9c2 cells.

PubMed

Xie, Yuxi; He, Yonggui; Cai, Zhiliang; Cai, Jianhang; Xi, Mengyao; Zhang, Yidong; Xi, Jinkun

2016-01-01

This study investigates whether inhibition of endoplasmic reticulum (ER) stress prevents opening of the mitochondrial permeability transition pore (mPTP) and evaluates the corresponding signaling pathways involved in this process. Exposure of cardiac H9c2 cells to 800 µM H 2 O 2 for 20 min opened mPTP in response to oxidative stress, as demonstrated by quenching of tetramethylrhodamine ethyl ester (TMRE) fluorescence. Oxidative stress-induced mPTP opening was rescued by the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) in a dose-dependent manner at low concentrations. The PI3K and PKG inhibitors LY294002 and KT5823 inhibited the effect of TUDCA on mPTP opening, suggesting the involvement of PI3K/Akt and PKG signaling pathways. TUDCA significantly increased glycogen synthase kinase 3 (GSK-3β) phosphorylation at Ser-9, with peak effect at 30 µM TUDCA. The level of GRP78 (ER chaperone) expression was significantly upregulated by 30 µM TUDCA. TUDCA-induced increases in Akt and GSK-3β phosphorylation were inhibited by LY294002, whereas KT5823 suppressed TUDCA-induced increases in VASP and GSK-3β phosphorylation. Oxidative stress severely affected cell morphology and ultrastructure. TUDCA prevented H 2 O 2 -induced ER swelling and mitochondrial damage. TUDCA boosted the viability of cells disrupted by ischemia/reperfusion (I/R), indicating that TUDCA eased reperfusion injury. However, TUDCA did not improve the viability of cells expressing the constitutively active GSK-3β mutant (GSK-3β-S9A-HA) that were subjected to I/R, suggesting an essential role of GSK-3β inactivation in TUDCA-mediated cardioprotection against reperfusion damage. These data indicate that ER stress inhibition prevents mPTP opening and attenuates reperfusion injury through GSK-3β inactivation. The PI3K/Akt and PKG pathways may mediate GSK-3β inactivation.

A cannabinoid receptor 2 agonist reduces blood-brain barrier damage via induction of MKP-1 after intracerebral hemorrhage in rats.

PubMed

Li, Lin; Yun, Debo; Zhang, Yuan; Tao, Yihao; Tan, Qiang; Qiao, Fei; Luo, Bo; Liu, Yi; Fan, Runjin; Xian, Jishu; Yu, Anyong

2018-06-07

The blood-brain barrier (BBB) disruption and the following development of brain edema, is the most life-threatening secondary injury after intracerebral hemorrhage (ICH). This study is to investigate a potential role and mechanism of JWH133, a selected cannabinoid receptor type2 (CB2R) agonist, on protecting blood-brain barrier integrity after ICH. 192 adult male Sprague-Dawley (SD) rats were randomly divided into Sham; ICH+Vehicle; ICH+JWH 1.0mg/kg, ICH+JWH 1.5mg/kg and ICH+JWH 2.0mg/kg; ICH+SR+JWH respectively. Animals were euthanized at 24 hours following western blots and immunofluorescence staining, we also examined the effect of JWH133 on the brain water contents, neurobehavioral deficits and blood brain barrier (BBB) permeability, meanwhile reassessed the inflammatory cytokines concentrations around the hematoma by enzyme-linked immunosorbent assay (ELISA) in each group. JWH133 (1.5mg/kg) administration ameliorated brain edema, neurological deficits and blood-brain barrier damage, as well as microglia activation. The expression of pro-inflammatory mediators interleukin 1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metallopeptidase-2/9(MMP2/9) were attenuated, but not monocyte chemoattractant protein-1 (MCP-1). Additionally, decreases in zonula occludens-1 (ZO-1) and claudin-5 expression were partially recovered by JWH133. Furthermore, JWH133 upregulated the expression level of MKP-1, which leads to the inhibition of MAPKs signaling pathway activation, especially for ERK and P38. However, these effects were reversed by pretreatment with a selective CB2R antagonist, SR144528. CB2R agonist alleviated neuroinflammation and protected blood-brain barrier permeability in a rat ICH model. Further molecular mechanisms revealed which is probably mediated by enhancing the expression of MKP-1, then inhibited MAPKs signal transduction. Copyright © 2018. Published by Elsevier B.V.

EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS.

PubMed

Xiao, Guizhen; Yuan, Fangfang; Geng, Yan; Qiu, Xiaowen; Liu, Zhifeng; Lu, Jiefu; Tang, Liqun; Zhang, Yali; Su, Lei

2015-10-01

Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37°C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography-mass selective detector. Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells. Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.

Physiological changes induced in four bacterial strains following oxidative stress.

PubMed

Baatout, S; De Boever, P; Mergeay, M

2006-01-01

In order to study the behaviour and resistance of bacteria under extreme conditions, physiological changes associated with oxidative stress were monitored using flow cytometry. The study was conducted to assess the maintenance of membrane integrity and potential as well as the esterase activity, the intracellular pH and the production of superoxide anions in four bacterial strains (Ralstonia metallidurans, Escherichia coli, Shewanella oneidensis and Deinococcus radiodurans). The strains were chosen for their potential usefulness in bioremediation. Suspensions of R. metallidurans, E. coli, S. oneidensis and D. radiodurans were submitted to 1 h oxidative stress (H2O2 at various concentrations from 0 to 880 mM). Cell membrane permeability (propidium iodide) and potential (rhodamine-123, 3,3'-dihexyloxacarbocyanine iodide), intracellular esterase activity (fluorescein diacetate), intracellular reactive oxygen species concentration (hydroethidine) and intracellular pH (carboxyflurorescein diacetate succinimidyl ester (5(6)) were monitored to evaluate the physiological state and the overall fitness of individual bacterial cells under oxidative stress. The four bacterial strains exhibited varying sensitivities towards H2O2. However, for all bacterial strains, some physiological damage could already be observed from 13.25 mM H2O2 onwards, in particular with regard to their membrane permeability. Depending on the bacterial strains, moderate to high physiological damage could be observed between 13.25 mM and 220 mM H2O2. Membrane potential, esterase activity, intracellular pH and production of superoxide anion production were considerably modified at high H2O2 concentrations in all four strains. In conclusion, we show that a range of significant physiological alterations occurs when bacteria are challenged with H2O2 and fluorescent staining methods coupled with flow cytometry are useful for monitoring the changes induced not only by oxidative stress but also by other stresses like temperature, radiation, pressure, pH, etc....

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2014-01-01

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

PubMed

Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

2015-01-05

The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the permeability criteria for BCS high permeability classification.

Alcoholism: A systemic proinflammatory condition

PubMed Central

González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

2014-01-01

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver. PMID:25356029

Plasma membrane repair and cellular damage control: the annexin survival kit.

PubMed

Draeger, Annette; Monastyrskaya, Katia; Babiychuk, Eduard B

2011-03-15

Plasmalemmal injury is a frequent event in the life of a cell. Physical disruption of the plasma membrane is common in cells that operate under conditions of mechanical stress. The permeability barrier can also be breached by chemical means: pathogens gain access to host cells by secreting pore-forming toxins and phospholipases, and the host's own immune system employs pore-forming proteins to eliminate both pathogens and the pathogen-invaded cells. In all cases, the influx of extracellular Ca(2+) is being sensed and interpreted as an "immediate danger" signal. Various Ca(2+)-dependent mechanisms are employed to enable plasma membrane repair. Extensively damaged regions of the plasma membrane can be patched with internal membranes delivered to the cell surface by exocytosis. Nucleated cells are capable of resealing their injured plasmalemma by endocytosis of the permeabilized site. Likewise, the shedding of membrane microparticles is thought to be involved in the physical elimination of pores. Membrane blebbing is a further damage-control mechanism, which is triggered after initial attempts at plasmalemmal resealing have failed. The members of the annexin protein family are ubiquitously expressed and function as intracellular Ca(2+) sensors. Most cells contain multiple annexins, which interact with distinct plasma membrane regions promoting membrane segregation, membrane fusion and--in combination with their individual Ca(2+)-sensitivity--allow spatially confined, graded responses to membrane injury. Copyright © 2011 Elsevier Inc. All rights reserved.

Use of flow cytometry to monitor cell damage and predict fermentation activity of dried yeasts.

PubMed

Attfield, P V; Kletsas, S; Veal, D A; van Rooijen, R; Bell, P J

2000-08-01

Viable dried yeast is used as an inoculum for many fermentations in the baking and wine industries. The fermentative activity of yeast in bread dough or grape must is a critical parameter of process efficiency. Here, it is shown that fluorescent stains and flow cytometry can be used in concert to predict the abilities of populations of dried bakers' and wine yeasts to ferment after rehydration. Fluorescent dyes that stain cells only if they have damaged membrane potential (oxonol) or have increased membrane permeability (propidium iodide) were used to analyse, by flow cytometry, populations of rehydrated yeasts. A strong relationship (r2 = 0.99) was found between the percentages of populations staining with the oxonol and the degree of cell membrane damage as measured by the more traditional method of leakage of intracellular compounds. There were also were good negative relationships (r2 > or = 0.83) between fermentation by rehydrated bakers' or wine dry yeasts and percentage of populations staining with either oxonol or propidium iodide. Fluorescent staining with flow cytometry confirmed that factors such as vigour of dried yeast mixing in water, soaking before stirring, rehydration in water or fermentation medium and temperature of rehydration have profound effects on subsequent yeast vitality. These experiments indicate the potential of flow cytometry as a rapid means of predicting the fermentation performance of dried bakers' and wine yeasts.

Alcoholism: a systemic proinflammatory condition.

PubMed

González-Reimers, Emilio; Santolaria-Fernández, Francisco; Martín-González, María Candelaria; Fernández-Rodríguez, Camino María; Quintero-Platt, Geraldine

2014-10-28

Excessive ethanol consumption affects virtually any organ, both by indirect and direct mechanisms. Considerable research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of alcoholism. These cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria, which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut permeability. Reactive oxygen species (ROS) that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of ethanol. The effects of this increased cytokine secretion and ROS generation lie far beyond liver damage. In addition to the classic consequences of endotoxemia associated with liver cirrhosis that were described several decades ago, important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain, bone, muscle, heart, lung, gonads, peripheral nerve, and pancreas. These effects are even seen in alcoholics without significant liver disease. Therefore, alcoholism can be viewed as an inflammatory condition, a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent disease. In this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

Distribution and nature of fault architecture in a layered sandstone and shale sequence: An example from the Moab fault, Utah

USGS Publications Warehouse

Davatzes, N.C.; Aydin, A.

2005-01-01

We examined the distribution of fault rock and damage zone structures in sandstone and shale along the Moab fault, a basin-scale normal fault with nearly 1 km (0.62 mi) of throw, in southeast Utah. We find that fault rock and damage zone structures vary along strike and dip. Variations are related to changes in fault geometry, faulted slip, lithology, and the mechanism of faulting. In sandstone, we differentiated two structural assemblages: (1) deformation bands, zones of deformation bands, and polished slip surfaces and (2) joints, sheared joints, and breccia. These structural assemblages result from the deformation band-based mechanism and the joint-based mechanism, respectively. Along the Moab fault, where both types of structures are present, joint-based deformation is always younger. Where shale is juxtaposed against the fault, a third faulting mechanism, smearing of shale by ductile deformation and associated shale fault rocks, occurs. Based on the knowledge of these three mechanisms, we projected the distribution of their structural products in three dimensions along idealized fault surfaces and evaluated the potential effect on fluid and hydrocarbon flow. We contend that these mechanisms could be used to facilitate predictions of fault and damage zone structures and their permeability from limited data sets. Copyright ?? 2005 by The American Association of Petroleum Geologists.

Neocrystallization, fabrics and age of clay minerals from an exposure of the Moab Fault, Utah

USGS Publications Warehouse

Solum, J.G.; van der Pluijm, B.A.; Peacor, D.R.

2005-01-01

Pronounced changes in clay mineral assemblages are preserved along the Moab Fault (Utah). Gouge is enriched up to ???40% in 1Md illite relative to protolith, whereas altered protolith in the damage zone is enriched ???40% in illite-smectite relative to gouge and up to ???50% relative to protolith. These mineralogical changes indicate that clay gouge is formed not solely through mechanical incorporation of protolith, but also through fault-related authigenesis. The timing of mineralization is determined using 40Ar/39Ar dating of size fractions of fault rocks with varying detrital and authigenic clay content. We applied Ar dating of illite-smectite samples, as well as a newer approach that uses illite polytypes. Our analysis yields overlapping, early Paleocene ages for neoformed (1Md) gouge illite (63??2 Ma) and illite-smectite in the damage zone (60??2 Ma), which are compatible with results elsewhere. These ages represent the latest period of major fault motion, and demonstrate that the fault fabrics are not the result of recent alteration. The clay fabrics in fault rocks are poorly developed, indicating that fluids were not confined to the fault zone by preferentially oriented clays; rather we propose that fluids in the illite-rich gouge were isolated by adjacent lower permeability, illite-smectite-bearing rocks in the damage zone. ?? 2005 Elsevier Ltd. All rights reserved.

CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation.

PubMed

Gan, Xueqi; Zhang, Ling; Liu, Beilei; Zhu, Zhuoli; He, Yuting; Chen, Junsheng; Zhu, Junfei; Yu, Haiyang

2018-04-20

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-α (TNF-α) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways.

Predictive modelling of fault related fracturing in carbonate damage-zones: analytical and numerical models of field data (Central Apennines, Italy)

NASA Astrophysics Data System (ADS)

Mannino, Irene; Cianfarra, Paola; Salvini, Francesco

2010-05-01

Permeability in carbonates is strongly influenced by the presence of brittle deformation patterns, i.e pressure-solution surfaces, extensional fractures, and faults. Carbonate rocks achieve fracturing both during diagenesis and tectonic processes. Attitude, spatial distribution and connectivity of brittle deformation features rule the secondary permeability of carbonatic rocks and therefore the accumulation and the pathway of deep fluids (ground-water, hydrocarbon). This is particularly true in fault zones, where the damage zone and the fault core show different hydraulic properties from the pristine rock as well as between them. To improve the knowledge of fault architecture and faults hydraulic properties we study the brittle deformation patterns related to fault kinematics in carbonate successions. In particular we focussed on the damage-zone fracturing evolution. Fieldwork was performed in Meso-Cenozoic carbonate units of the Latium-Abruzzi Platform, Central Apennines, Italy. These units represent field analogues of rock reservoir in the Southern Apennines. We combine the study of rock physical characteristics of 22 faults and quantitative analyses of brittle deformation for the same faults, including bedding attitudes, fracturing type, attitudes, and spatial intensity distribution by using the dimension/spacing ratio, namely H/S ratio where H is the dimension of the fracture and S is the spacing between two analogous fractures of the same set. Statistical analyses of structural data (stereonets, contouring and H/S transect) were performed to infer a focussed, general algorithm that describes the expected intensity of fracturing process. The analytical model was fit to field measurements by a Montecarlo-convergent approach. This method proved a useful tool to quantify complex relations with a high number of variables. It creates a large sequence of possible solution parameters and results are compared with field data. For each item an error mean value is computed (RMS), representing the effectiveness of the fit and so the validity of this analysis. Eventually, the method selects the set of parameters that produced the least values. The tested algorithm describes the expected H/S values as a function of the distance from the fault core (D), the clay content (S), and the fault throw (T). The preliminary results of the Montecarlo inversion show that the distance (D) has the most effective influence in the H/S spatial distribution and the H/S value decreases with the distance from the fault-core. The rheological parameter shows a value similar to the diagenetic H/S values (1-1.5). The resulting equation has a reasonable RMS value of 0.116. The results of the Montecarlo models were finally implemented in FRAP, a fault environment modelling software. It is a true 4D tool that can predict stress conditions and permeability architecture associated to a given faults during single or multiple tectonic events. We present some models of fault-related fracturing among the studied faults performed by FRAP and we compare them with the field measurements, to test the validity of our methodology.

Applying 3D Full Waveform Inversion in resolving fracture damage zones around a modelled geological disposal facility in granite

NASA Astrophysics Data System (ADS)

Bentham, H. L. M.; Morgan, J. V.; Angus, D. A.

2016-12-01

The UK has a large volume of high level and intermediate level radioactive waste and government policy is to dispose of this waste in a Geological Disposal Facility (GDF). This will be a highly-engineered facility capable of isolating radioactive waste within multiple protective barriers, deep underground, to ensure that no harmful quantities of radioactivity ever reach the surface environment. Although no specific GDF site in the UK has been chosen, granite is one of the candidate host rocks due to its strength, in engineering terms, and because of its low permeability in consideration of groundwater movement. We design time-lapse seismic surveys to characterise geological models of naturally fractured granite with GDF-related tunnel damage zones at a potential disposal depth of 1000 m (the UK GDF might be shallower). Additionally, we use effective medium models to calculate the velocity change when the fracture density is increased in the damage zones, and find a reduction of 60 m/s in P-wave velocity when the fracture density is doubled. Next, we simulate seismic surveys and apply 3D Full Waveform Inversion (FWI) to see how well we can recover the low-velocity damage zones. Furthermore we evaluate the effectiveness of using a survey design consisting of surface and tunnel receivers (a combined array) to resolve the target. After applying FWI we find the velocity anomaly within the damage zone can be resolved to within 2 m/s (3%) and the shape of the damage zone is resolved to 12.5 m (within a single grid cell). Using the combined array we are able to resolve the anomaly strength and shape more completely. When we add further complexity to the model by including tunnel infrastructure, we conclude the combined array is essential in recovering the tunnel damage zone. Our findings show that it is beneficial to use 3D FWI and novel survey designs for characterising subtle variations as may be present in granite, information that could assist in the GDF site selection process and also with GDF design.

Permeability of stylolite-bearing chalk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lind, I.; Nykjaer, O.; Priisholm, S.

1994-11-01

Permeabilities were measured on core plugs from stylolite-bearing chalk of the Gorm field in the Danish North Sea. Air and liquid permeabilities were measured in directions parallel to and perpendicular to the stylolite surface. Permeability was measured with sleeve pressure equal to in-situ reservoir stress. Permeabilities of plugs with stylolites but without stylolite-associated fractures were equal in the two directions. The permeability is equal to the matrix permeability of non-stylolite-bearing chalk. In contrast, when fractures were associated with the stylolites, permeability was enhanced. The enhancement was most significant in the horizontal direction parallel to the stylolites.

The transition from brittle faulting to cataclastic flow: Permeability evolution

NASA Astrophysics Data System (ADS)

Zhu, Wenlu; Wong, Teng-Fong

1997-02-01

Triaxial compression experiments were conducted to investigate influences of stress and failure mode on axial permeability of five sandstones with porosities ranging from 15% to 35%. In the cataclastic flow regime, permeability and porosity changes closely track one another. A drastic decrease in permeability was triggered by the onset of shear-enhanced compaction caused by grain crushing and pore collapse. The compactive yield stress C* maps out a boundary in stress space separating two different types of permeability evolution. Before C* is attained, permeability and porosity both decrease with increasing effective mean stress, but they are independent of deviatoric stresses. However, with loading beyond C*, both permeability and porosity changes are strongly dependent on the deviatoric and effective mean stresses. In the brittle faulting regime, permeability and porosity changes are more complex. Before the onset of shear-induced dilation C', both permeability and porosity decrease with increasing effective mean stress. Beyond C', permeability may actually decrease in a dilating rock prior to brittle failure. After the peak stress has been attained, the development of a relatively impermeable shear band causes an accelerated decrease of permeability. Permeability evolution in porous sandstones is compared with that in low-porosity crystalline rocks. A conceptual model for the coupling of deformation and fluid transport is proposed in the form of a deformation-permeability map.

Use of plasma proteins as solubilizing agents in in vitro permeability experiments: correction for unbound drug concentration using the reciprocal permeability approach.

PubMed

Katneni, Kasiram; Charman, Susan A; Porter, Christopher J H

2008-01-01

The purpose of the present study was to explore the applicability of the reciprocal permeability approach to correct for changes in thermodynamic activity when in vitro permeability data are generated in the presence of plasma proteins. Diazepam (DIA), digoxin (DIG), and propranolol (PRO) permeability was assessed in the presence of bovine serum albumin (BSA) and bovine alpha-1-acid glycoprotein (AAG). The reciprocal permeability approach was subsequently employed to calculate the true permeability coefficient (Papp(corr)) and the operational protein association constant (nK(a)). For BSA binding, good agreement was observed between the Papp(corr) values and Papp values obtained in the absence of protein. For PRO and AAG, where binding affinity was high, deviation in the reciprocal permeability plots was evident suggesting ligand depletion at low drug/high protein concentrations. Bidirectional DIG permeability data in the presence of either BSA or AAG indicated that neither protein had an effect on the efflux transporters involved in DIG permeability. The data suggest that plasma proteins can be utilized in permeability experiments with no adverse effects on transporter function and that the reciprocal permeability approach can be used to correct permeability data for changes in unbound drug concentration. c) 2007 Wiley-Liss, Inc.

Controlled-Turbulence Bioreactors

NASA Technical Reports Server (NTRS)

Wolf, David A.; Schwartz, Ray; Trinh, Tinh

1989-01-01

Two versions of bioreactor vessel provide steady supplies of oxygen and nutrients with little turbulence. Suspends cells in environment needed for sustenance and growth, while inflicting less damage from agitation and bubbling than do propeller-stirred reactors. Gentle environments in new reactors well suited to delicate mammalian cells. One reactor kept human kidney cells alive for as long as 11 days. Cells grow on carrier beads suspended in liquid culture medium that fills cylindrical housing. Rotating vanes - inside vessel but outside filter - gently circulates nutrient medium. Vessel stationary; magnetic clutch drives filter cylinder and vanes. Another reactor creates even less turbulence. Oxygen-permeable tubing wrapped around rod extending along central axis. Small external pump feeds oxygen to tubing through rotary coupling, and oxygen diffuses into liquid medium.

Oxidative Stress and Lung Ischemia-Reperfusion Injury

PubMed Central

Ferrari, Renata Salatti; Andrade, Cristiano Feijó

2015-01-01

Ischemia-reperfusion (IR) injury is directly related to the formation of reactive oxygen species (ROS), endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients. PMID:26161240

[Research of bornrol promote drugs through blood-brain barrier].

PubMed

Lv, Xuxiao; Sun, Mingjiang; Sun, Fengzhi

2012-04-01

Malignant tumor, epilepsy, dementia, cerebral ischemia and other brain diseases have very high rates of disability and mortality. Currently, many drugs are developed to treat such diseases and the effect is obviously. But they can not achieve the purpose to control these diseases because many of the drugs can not pass through the blood-brain barrier (BBB). Therefore, the treatment is not good. Borneol as the represent of the aromatic resuscitation medicine, it has strong fat-soluble active ingredients, small molecular weight, volatile and through the BBB quickly. It can also promote other therapeutic drugs through the BBB. It has two-ways regulations on BBB permeability and the damage of brain tissue is small, this have important theoretical significances and application values.

Design, synthesis and pharmacological evaluation of (E)-3,4-dihydroxy styryl sulfonamides derivatives as multifunctional neuroprotective agents against oxidative and inflammatory injury.

PubMed

Ning, Xianling; Guo, Ying; Ma, Xiaoyan; Zhu, Renzong; Tian, Chao; Zhang, Zhili; Wang, Xiaowei; Ma, Zhizhong; Liu, Junyi

2013-09-01

A novel class of (E)-3,4-dihydroxy styryl sulfonamides and their 3,4-diacetylated derivatives as caffeic acid phenethyl ester (CAPE) analogs was designed and prepared for improving stability and solubility of the lead compound. Their neuroprotective properties were assessed by several models. The results showed that target compounds displayed positive free radical quenching abilities, superior to that of CAPE. Compounds 6j-k and 7j-k demonstrated remarkable protection effects against damage induced by hydrogen peroxide which were apparently stronger than that of CAPE. Most of target compounds could inhibit nitric oxide production. Additionally, target compounds showed high blood-brain barrier permeability. Copyright © 2013. Published by Elsevier Ltd.