Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

PubMed Central

2015-01-01

Hepatocellular carcinoma (HCC) is the most common form of liver cancer (~80%), and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF) on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12) signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients. PMID:26560447

Cytokine signalling in rat pulp interstitial fluid and transcapillary fluid exchange during lipopolysaccharide-induced acute inflammation

PubMed Central

Bletsa, Athanasia; Berggreen, Ellen; Fristad, Inge; Tenstad, Olav; Wiig, Helge

2006-01-01

The dental pulp consists of loose connective tissue encased in rigid dentinal walls. Because of its topography the tissue has low interstitial compliance and limited capacity to expand during fluid volume changes. Due to limitations regarding access to interstitial fluid, basic knowledge on transcapillary fluid transport parameters is lacking for this organ. The scope of this project was dual: first we aimed at establishing a method for isolation of pulp interstitial fluid (IF), and second we applied the method in rats subjected to lipopolysaccharide (LPS)-induced endotoxaemia. The aim was to measure colloid osmotic pressure (COP) and pro-inflammatory cytokines in the pulp IF during acute inflammation. Fluid volumes and pulpal blood flow (PBF) were measured to obtain more information about microcirculatory changes that take place in this pulpitis model. By centrifugation of incisor pulp at 239 g we were able to extract fluid representative for IF. Pulp IF had a relative high control COP (∼83% of plasma COP) and was similar to plasma COP 3 h after LPS challenge. The pulp exhibited a high content of IF (0.60 ± 0.03 ml (g wet weight)−1) and a vascular volume of 0.03 ± 0.01 ml (g w.w.)−1 No differences were observed in the distribution of fluid volumes after 1.5 and 3 h LPS exposure. PBF and systemic blood pressure dropped significantly after LPS administration. PBF remained low whereas systemic blood pressure was re-established during the 3-h period, implying organ dysfunction. There was a differential pattern of cytokine expression in pulp IF and serum with cytokines such as IL-1α, IL-1β and TNF-α locally produced, whereas others such as IFN-γ and IL-6 were produced systemically and probably spilled over to the pulp IF after LPS exposure. Our findings show that pulp IF can be isolated by centrifugation and that this method is useful when studying fluid balance and extracellular signalling mechanisms in the dental pulp in normal and pathological conditions. PMID:16527857

Blood and interstitial flow in the hierarchical pore space architecture of bone tissue.

PubMed

Cowin, Stephen C; Cardoso, Luis

2015-03-18

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

Blood and Interstitial flow in the hierarchical pore space architecture of bone tissue

PubMed Central

Cowin, Stephen C.; Cardoso, Luis

2015-01-01

There are two main types of fluid in bone tissue, blood and interstitial fluid. The chemical composition of these fluids varies with time and location in bone. Blood arrives through the arterial system containing oxygen and other nutrients and the blood components depart via the venous system containing less oxygen and reduced nutrition. Within the bone, as within other tissues, substances pass from the blood through the arterial walls into the interstitial fluid. The movement of the interstitial fluid carries these substances to the cells within the bone and, at the same time, carries off the waste materials from the cells. Bone tissue would not live without these fluid movements. The development of a model for poroelastic materials with hierarchical pore space architecture for the description of blood flow and interstitial fluid flow in living bone tissue is reviewed. The model is applied to the problem of determining the exchange of pore fluid between the vascular porosity and the lacunar-canalicular porosity in bone tissue due to cyclic mechanical loading and blood pressure. These results are basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. PMID:25666410

Investigations of lymphatic drainage from the interstitial space

NASA Astrophysics Data System (ADS)

Jayathungage Don, Tharanga; Richard Clarke Collaboration; John Cater Collaboration; Vinod Suresh Collaboration

2017-11-01

The lymphatic system is a highly complex biological system that facilitates the drainage of excess fluid in body tissues. In addition, it is an integral part of the immunological control system. Understanding the mechanisms of fluid absorption from the interstitial space and flow through the initial lymphatics is important to treat several pathological conditions. The main focus of this study is to computationally model the lymphatic drainage from the interstitial space. The model has been developed to consider a 3D lymphatic network and uses biological data to inform the creation of realistic geometries for the lymphatic capillary networks. We approximate the interstitial space as a porous region and the lymphatic vessel walls as permeable surfaces. The dynamics of the flow is approximated by Darcy's law in the interstitium and the Navier-Stokes equations in the lymphatic capillary lumen. The proposed model examines lymph drainage as a function of pressure gradient. In addition, we have examined the effects of interstitial and lymphatic wall permeabilities on the lymph drainage and the solute transportation in the model. The computational results are in accordance with the available experimental measurements.

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity

NASA Technical Reports Server (NTRS)

Verbanck, S.; Larsson, H.; Linnarsson, D.; Prisk, G. K.; West, J. B.; Paiva, M.

1997-01-01

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood-brain barrier: [17O]H2O JJVCPE MRI study.

PubMed

Huber, Vincent J; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L; Nakada, Tsutomu

2018-06-13

The blood-brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow-Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow-Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB.

Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.

PubMed

Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf

2017-08-22

The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Transcapillary fluid shifts in head and neck tissues during and after simulated microgravity

NASA Technical Reports Server (NTRS)

Parazynski, S. E.; Hargens, Alan R.; Tucker, B.; Aratow, M.; Styf, J.; Crenshaw, A.

1991-01-01

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during, and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip: capillary pressures increased from 27.2 +/- 5 mm Hg pre-HDT to 33.9 +/- 1.7 mm Hg by the end of tilt. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values, despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr. These results indicate that facial edema resulting from HDT is primarily caused by elevated capillary pressures and decreased plasma colloid osmotic pressures. Elevation of cephalic capillary pressures sustained for 4 hr after HDT suggests that there is a compensatory vasodilation to maintain microvascular perfusion. The negativity of interstitial fluid pressures above heart level also has implications for the maintenance of tissue fluid balance in upright posture.

In vivo interstitial glucose characterization and monitoring in the skin by ATR-FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Skrebova Eikje, Natalja

2011-03-01

Successful development of real-time non-invasive glucose monitoring would represent a major advancement not only in the treatment and management of patients with diabetes mellitus and carbohydrate metabolism disorders, but also for understanding in those biochemical, metabolic and (patho-)physiological processes of glucose at the molecular level in vivo. Here, ATR-FTIR spectroscopy technique has been challenged not only for in vivo measurement of interstitial glucose levels, but also for their non-invasive molecular qualitative and quantitative comparative characterization in the skin tissue. The results, based on calculated mean values of determined 5 glucose-specific peaks in the glucose-related 1000-1160 cm-1 region, showed intra- and inter-subject differences in interstitial glucose activity levels with their changes at different times and doses of OGTT, while raising questions about the relationships between interstitial and blood glucose levels. In conclusion, the introduction of ATR-FTIR spectroscopy technique has opened up an access to the interstitial fluid space in the skin tissue for interstitial glucose characterization and monitoring in vivo. Though interstitial versus blood glucose monitoring has different characteristics, it can be argued that accurate and precise measurements of interstitial glucose levels may be more important clinically.

In vivo wireless ethanol vapor detection in the Wistar rat

PubMed Central

Cheney, C. Parks; Srijanto, B.; Hedden, D. L.; Gehl, A.; Ferrell, T. L.; Schultz, J.; Engleman, E. A.; McBride, W. J.; O'Connor, S.

2009-01-01

Traditional alcohol studies measure blood alcohol concentration to elucidate the biomedical factors that contribute to alcohol abuse and alcoholism. These measurements require large and expensive equipment, are labor intensive, and are disruptive to the subject. To alleviate these problems, we have developed an implantable, wireless biosensor that is capable of measuring alcohol levels for up to six weeks. Ethanol levels were measured in vivo in the interstitial fluid of a Wistar rat after administering 1 g/kg and 2 g/kg ethanol by intraperitoneal (IP) injection. The data were transmitted wirelessly using a biosensor selective for alcohol detection. A low-power piezoresistive microcantilever sensor array was used with a polymer coating suitable for measuring ethanol concentrations at 100% humidity over several hours. A hydrophobic, vapor permeable nanopore membrane was used to screen liquid and ions while allowing vapor to pass to the sensor from the subcutaneous interstitial fluid. PMID:20161283

Increased negatively of interstitial fluid pressure in rat skin contributes to the edema formation induced by Zymosan.

PubMed

Ostgaard, G; Reed, R K

1993-11-01

Increased negatively of interstitial fluid pressure (Pif) contributes to rapid edema formation in several acute inflammatory reactions attesting to an "active" role for the loose connective tissues in the transcapillary fluid exchange and edema formation under these circumstances. The present study reports the effect of the complement activator Zymosan on Pif, transcapillary fluid, and albumin flux. Micropipettes (tip diameter 5 to 7 microns) connected to a servo-controlled counterpressure system were used to measure Pif in rat dermis. When compared to saline injection, subdermal injection of 1 mg Zymosan in 10 microliters 0.15 M NaCl increased total tissue water by 1.6 ml/g dry weight in 5 min, corresponding to about 150% increase in interstitial fluid volume. Pif increased from +0.4 to +3.7 mm Hg. Increased negativity of Pif can be masked by the edema formation which will increase Pif. Measurements were therefore also performed after circulatory arrest, when transcapillary fluid flux and edema formation are abolished. Using this experimental protocol Pif fell from +0.3 mm Hg to -2.5 mm Hg 5 min after subdermal injection of Zymosan and remained at this level throughout the observation period of 90 min. Injection of saline alone after circulatory arrest increased Pif transiently by about 1 mm Hg. Thus, subdermal injection of Zymosan causes increased negativity of Pif by about 4 mm Hg. Although the lowering of Pif itself will explain a minor part of the increased fluid filtration, the results attest to the role of loose connective tissues being active in the edema-generating process also in the inflammatory reaction induced by Zymosan.

Aquaporin-4 facilitator TGN-073 promotes interstitial fluid circulation within the blood–brain barrier: [17O]H2O JJVCPE MRI study

PubMed Central

Huber, Vincent J.; Igarashi, Hironaka; Ueki, Satoshi; Kwee, Ingrid L.

2018-01-01

The blood–brain barrier (BBB), which imposes significant water permeability restriction, effectively isolates the brain from the systemic circulation. Seemingly paradoxical, the abundance of aquaporin-4 (AQP-4) on the inside of the BBB strongly indicates the presence of unique water dynamics essential for brain function. On the basis of the highly specific localization of AQP-4, namely, astrocyte end feet at the glia limitans externa and pericapillary Virchow–Robin space, we hypothesized that the AQP-4 system serves as an interstitial fluid circulator, moving interstitial fluid from the glia limitans externa to pericapillary Virchow–Robin space to ensure proper glymphatic flow draining into the cerebrospinal fluid. The hypothesis was tested directly using the AQP-4 facilitator TGN-073 developed in our laboratory, and [17O]H2O JJ vicinal coupling proton exchange MRI, a method capable of tracing water molecules delivered into the blood circulation. The results unambiguously showed that facilitation of AQP-4 by TGN-073 increased turnover of interstitial fluid through the system, resulting in a significant reduction in [17O]H2O contents of cortex with normal flux into the cerebrospinal fluid. The study further suggested that in addition to providing the necessary water for proper glymphatic flow, the AQP-4 system produces a water gradient within the interstitial space promoting circulation of interstitial fluid within the BBB. PMID:29481527

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow

PubMed Central

Kwee, Ingrid L.

2017-01-01

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics. PMID:28820467

Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

PubMed

Nakada, Tsutomu; Kwee, Ingrid L; Igarashi, Hironaka; Suzuki, Yuji

2017-08-18

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics.

Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.

PubMed

Miller, Wayne L; Mullan, Brian P

2014-06-01

This study sought to quantitate total blood volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of volume overload, and the magnitude and distribution of blood volume and body water changes following diuretic therapy. The accurate assessment and management of volume overload in patients with DCHF remains problematic. TBV was measured by a radiolabeled-albumin dilution technique with intravascular volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine interstitial volume contribution to total fluid loss. Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular volume post-diuretic therapy despite large reductions in body weight. Mobilization of interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular volume, however, remained increased at dismissal. The extent, composition, and distribution of volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed volume management with respect to a goal of treating to euvolemia. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Research into the Physiology of Cerebrospinal Fluid Reaches a New Horizon: Intimate Exchange between Cerebrospinal Fluid and Interstitial Fluid May Contribute to Maintenance of Homeostasis in the Central Nervous System

PubMed Central

MATSUMAE, Mitsunori; SATO, Osamu; HIRAYAMA, Akihiro; HAYASHI, Naokazu; TAKIZAWA, Ken; ATSUMI, Hideki; SORIMACHI, Takatoshi

2016-01-01

Cerebrospinal fluid (CSF) plays an essential role in maintaining the homeostasis of the central nervous system. The functions of CSF include: (1) buoyancy of the brain, spinal cord, and nerves; (2) volume adjustment in the cranial cavity; (3) nutrient transport; (4) protein or peptide transport; (5) brain volume regulation through osmoregulation; (6) buffering effect against external forces; (7) signal transduction; (8) drug transport; (9) immune system control; (10) elimination of metabolites and unnecessary substances; and finally (11) cooling of heat generated by neural activity. For CSF to fully mediate these functions, fluid-like movement in the ventricles and subarachnoid space is necessary. Furthermore, the relationship between the behaviors of CSF and interstitial fluid in the brain and spinal cord is important. In this review, we will present classical studies on CSF circulation from its discovery over 2,000 years ago, and will subsequently introduce functions that were recently discovered such as CSF production and absorption, water molecule movement in the interstitial space, exchange between interstitial fluid and CSF, and drainage of CSF and interstitial fluid into both the venous and the lymphatic systems. Finally, we will summarize future challenges in research. This review includes articles published up to February 2016. PMID:27245177

The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components

PubMed Central

Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

2005-01-01

Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5–7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 ± 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 ± 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by ∼50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume. PMID:15994186

The interstitial distribution of macromolecules in rat tumours is influenced by the negatively charged matrix components.

PubMed

Wiig, Helge; Gyenge, Christina C; Tenstad, Olav

2005-09-01

Knowledge of macromolecular distribution volumes is essential in understanding fluid transport within normal and pathological tissues. In this study in vivo we determined the distribution volumes of several macromolecules, including one monoclonal antibody, in tumours and tested whether charges associated with the tumour extracellular matrix influence their available volumes. Steady state levels of the monoclonal antibody trastuzumab (Herceptin) (pI = 9.2), IgG (pI = 7.6) as well as native (pI = 5.0) and cationized albumin (pI = 7.6) were established in rats bearing dimethylbenzanthracene (DMBA)-induced mammary tumours by continuous infusion using osmotic minipumps. After a 5-7 day infusion period, the rats were nephrectomized and the extracellular volume was determined with 51Cr-labelled EDTA. Plasma volumes were measured with 125I-labelled human serum albumin or rat IgM in a separate series. Steady state concentrations of probes were determined in the interstitial fluid that was isolated by centrifugation from tumours or by post mortem wick implantation in the back skin. Calculations were made for interstitial fluid volume (Vi), along with the available (Va/Vi) and excluded (Ve/Vi) relative interstitial volume fractions. The Ve/Vi for the positively charged trastuzumab in tumours averaged 0.29 +/- 0.03 (n = 16), a value which was significantly lower than the corresponding one for IgG of 0.36 +/- 0.02 (n = 16). Native albumin was excluded from 38% of the tumour interstitial fluid, whereas cationization of albumin reduced the excluded volume by approximately 50%. Our experiments suggest that the tumour interstitium acts as a negatively charged matrix and is an important factor in determining the macromolecular distribution volume.

Transcapillary fluid shifts in tissues of the head and neck during and after simulated microgravity

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Tucker, B.; Aratow, M.; Styf, J.; Crenshaw, A.; Parazynski, S. E.

1991-01-01

To understand the mechanism, magnitude, and time course of facial puffiness that occurs in microgravity, seven male subjects were tilted 6 degrees head down for 8 hr, and all four Starling transcapillary pressures were directly measured before, during , and after tilt. Head-down tilt (HDT) caused facial edema and a significant elevation of microvascular pressures measured in the lower lip. Subcutaneous and intramuscular interstitial fluid pressures in the neck also increased as a result of HDT, while interstitial fluid colloid osmotic pressures remained unchanged. Plasma colloid osmotic pressures dropped significantly after 4 hr of HDT, suggesting a transition from fluid filtration to absorption in capillary beds between the heart and feet during HDT. After 4 hr of seated recovery from HDT, microvascular pressures remained significantly elevated by 5 to 8 mm Hg above baseline values despite a significant HDT diuresis and the orthostatic challenge of an upright, seated posture. During the control (baseline) period, urine output was 46.7 ml/hr; during HDT, it was 126.5 ml/hr.

The effect of interstitial pressure on tumor growth: coupling with the blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; McDougall, Steven R.; Chaplain, Mark A.J.; Cristini, Vittorio; Lowengrub, John

2013-01-01

The flow of interstitial fluid and the associated interstitial fluid pressure (IFP) in solid tumors and surrounding host tissues have been identified as critical elements in cancer growth and vascularization. Both experimental and theoretical studies have shown that tumors may present elevated IFP, which can be a formidable physical barrier for delivery of cell nutrients and small molecules into the tumor. Elevated IFP may also exacerbate gradients of biochemical signals such as angiogenic factors released by tumors into the surrounding tissues. These studies have helped to understand both biochemical signaling and treatment prognosis. Building upon previous work, here we develop a vascular tumor growth model by coupling a continuous growth model with a discrete angiogenesis model. We include fluid/oxygen extravasation as well as a continuous lymphatic field, and study the micro-environmental fluid dynamics and their effect on tumor growth by accounting for blood flow, transcapillary fluid flux, interstitial fluid flow, and lymphatic drainage. We thus elucidate further the non-trivial relationship between the key elements contributing to the effects of interstitial pressure in solid tumors. In particular, we study the effect of IFP on oxygen extravasation and show that small blood/lymphatic vessel resistance and collapse may contribute to lower transcapillary fluid/oxygen flux, thus decreasing the rate of tumor growth. We also investigate the effect of tumor vascular pathologies, including elevated vascular and interstitial hydraulic conductivities inside the tumor as well as diminished osmotic pressure differences, on the fluid flow across the tumor capillary bed, the lymphatic drainage, and the IFP. Our results reveal that elevated interstitial hydraulic conductivity together with poor lymphatic function is the root cause of the development of plateau profiles of the IFP in the tumor, which have been observed in experiments, and contributes to a more uniform distribution of oxygen, solid tumor pressure and a broad-based collapse of the tumor lymphatics. We also find that the rate that IFF is fluxed into the lymphatics and host tissue is largely controlled by an elevated vascular hydraulic conductivity in the tumor. We discuss the implications of these results on microenvironmental transport barriers, and the tumor invasive and metastatic potential. Our results suggest the possibility of developing strategies of targeting tumor cells based on the cues in the interstitial fluid. PMID:23220211

Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement.

PubMed

Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Hamaguchi, Tomoya; Matsuo, Toshihiro; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi; Sato, Toshiyuki; Okada, Seiki; Tomita, Koji; Matsuhisa, Munehide; Kaneto, Hideaki; Kosugi, Keisuke; Maegawa, Hiroshi; Nakajima, Hiromu; Kashiwagi, Atsunori

2013-05-01

We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202-610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice. © 2013 Diabetes Technology Society.

Evaluation of a Minimally Invasive System for Measuring Glucose Area under the Curve during Oral Glucose Tolerance Tests: Usefulness of Sweat Monitoring for Precise Measurement

PubMed Central

Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Hamaguchi, Tomoya; Toshihiro, Matsuo; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi; Sato, Toshiyuki; Okada, Seiki; Tomita, Koji; Matsuhisa, Munehide; Kaneto, Hideaki; Kosugi, Keisuke; Maegawa, Hiroshi; Nakajima, Hiromu; Kashiwagi, Atsunori

2013-01-01

Aims: We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs). Materials and Methods: Fifty diabetes mellitus inpatients and 10 healthy subjects undergoing the 75 g OGTT were included. Two sites on the forearm were pretreated with microneedle arrays, then hydrogels for interstitial fluid extraction were placed on the treated sites. Simultaneously, hydrogels for sweat monitoring were placed on untreated sites near the treated sites. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference AUC values. Using MIET, IG AUC was calculated from extracted glucose and sodium ion levels after attachment of the hydrogel for 2 h. Results: Good correlation between IG AUC measurements using MIET and reference AUCs measured using PG levels was confirmed over a wide AUC range (202–610 mg/h/dl) after correction for the sweat-induced error detected by the hydrogel patches on the nonpretreated skin. Strong correlation between IG AUC and peak glucose levels indicates that glucose spikes can be easily detected by this system. Conclusion: We confirmed the effectiveness of a sweat monitoring patch for precise AUC measurement using MIET. This novel, easy-to-use system has potential for glucose excursion evaluation in daily clinical practice. PMID:23759401

An Effective Histological Staining Process to Visualize Bone Interstitial Fluid Space Using Confocal Microscopy

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2009-01-01

Bone is a composite porous material with two functional levels of porosity: the vascular porosity that surrounds blood vessels and the lacunar-canalicular porosity that surrounds the osteocytes. Both the vascular porosity and lacunar-canalicular porosity are directly involved in interstitial fluid flow, thought to play an important role in bone’s maintenance. Because of the small dimensions of the lacunar-canalicular porosity, interstitial fluid space has been difficult to visualize and quantify. We report a new staining protocol that is reliable and easily reproducible, using fluorescein isothiocyanate (FITC) as a probe visualized by confocal microscopy. Reconstructed FITC-stained cross sections enable effective visualization of bone microstructure and microporosities. This new staining process can be used to analyze interstitial fluid space, providing high-resolution quantification of the vascular pores and the lacunar-canalicular network of cortical and cancellous bone. PMID:19442607

Isoflurane in contrast to propofol promotes fluid extravasation during cardiopulmonary bypass in pigs.

PubMed

Brekke, Hege Kristin; Hammersborg, Stig Morten; Lundemoen, Steinar; Mongstad, Arve; Kvalheim, Venny Lise; Haugen, Oddbjørn; Husby, Paul

2013-10-01

A highly positive intraoperative fluid balance should be prevented as it negatively impacts patient outcome. Analysis of volume-kinetics has identified an increase in interstitial fluid volume after crystalloid fluid loading during isoflurane anesthesia. Isoflurane has also been associated with postoperative hypoxemia and may be associated with an increase in alveolar epithelial permeability, edema formation, and hindered oxygen exchange. In this article, the authors compare fluid extravasation rates before and during cardiopulmonary bypass (CPB) with isoflurane- versus propofol-based anesthesia. Fourteen pigs underwent 2 h of tepid CPB with propofol (P-group; n = 7) or isoflurane anesthesia (I-group; n = 7). Fluid requirements, plasma volume, colloid osmotic pressures in plasma and interstitial fluid, hematocrit levels, and total tissue water content were recorded, and fluid extravasation rates calculated. Fluid extravasation rates increased in the I-group from the pre-CPB level of 0.27 (0.13) to 0.92 (0.36) ml·kg·min, but remained essentially unchanged in the P-group with significant between-group differences during CPB (pb = 0.002). The results are supported by corresponding changes in interstitial colloid osmotic pressure and total tissue water content. During CPB, isoflurane, in contrast to propofol, significantly contributes to a general increase in fluid shifts from the intravascular to the interstitial space with edema formation and a possible negative impact on postoperative organ function.

Changes in blood flow and cellular metabolism at a myofascial trigger point with trigger point release (ischemic compression): a proof-of-principle pilot study

PubMed Central

Moraska, Albert F.; Hickner, Robert C.; Kohrt, Wendy M.; Brewer, Alan

2012-01-01

Objective To demonstrate proof-of-principle measurement for physiological change within an active myofascial trigger point (MTrP) undergoing trigger point release (ischemic compression). Design Interstitial fluid was sampled continuously at a trigger point before and after intervention. Setting A biomedical research clinic at a university hospital. Participants Two subjects from a pain clinic presenting with chronic headache pain. Interventions A single microdialysis catheter was inserted into an active MTrP of the upper trapezius to allow for continuous sampling of interstitial fluid before and after application of trigger point therapy by a massage therapist. Main Outcome Measures Procedural success, pain tolerance, feasibility of intervention during sample collection, determination of physiologically relevant values for local blood flow, as well as glucose and lactate concentrations. Results Both patients tolerated the microdialysis probe insertion into the MTrP and treatment intervention without complication. Glucose and lactate concentrations were measured in the physiological range. Following intervention, a sustained increase in lactate was noted for both subjects. Conclusions Identifying physiological constituents of MTrP’s following intervention is an important step toward understanding pathophysiology and resolution of myofascial pain. The present study forwards that aim by showing proof-of-concept for collection of interstitial fluid from an MTrP before and after intervention can be accomplished using microdialysis, thus providing methodological insight toward treatment mechanism and pain resolution. Of the biomarkers measured in this study, lactate may be the most relevant for detection and treatment of abnormalities in the MTrP. PMID:22975226

Roles of interstitial fluid pH in diabetes mellitus: Glycolysis and mitochondrial function

PubMed Central

Marunaka, Yoshinori

2015-01-01

The pH of body fluids is one the most important key factors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body (interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body (interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis (honeybee product) diet. PMID:25685283

Evaluation of postprandial glucose excursion using a novel minimally invasive glucose area-under-the-curve monitoring system.

PubMed

Kuranuki, Sachi; Sato, Toshiyuki; Okada, Seiki; Hosoya, Samiko; Seko, Akinobu; Sugihara, Kaya; Nakamura, Teiji

2013-01-01

To develop a minimally invasive interstitial fluid extraction technology (MIET) to monitor postprandial glucose area under the curve (AUC) without blood sampling, we evaluated the accuracy of glucose AUC measured by MIET and compared with that by blood sampling after food intake. Interstitial fluid glucose AUC (IG-AUC) following consumption of 6 different types of foods was measured by MIET. MIET consisted of stamping microneedle arrays, placing hydrogel patches on the areas, and calculating IG-AUC based on glucose levels in the hydrogels. Glycemic index (GI) was determined using IG-AUC and reference AUC measured by blood sampling. IG-AUC strongly correlated with reference AUC (R = 0.91), and GI determined using IG-AUC showed good correlation with that determined by reference AUC (R = 0.88). IG-AUC obtained by MIET can accurately predict the postprandial glucose excursion without blood sampling. In addition, feasibility of GI measurement by MIET was confirmed.

Predictive models for pressure-driven fluid infusions into brain parenchyma

NASA Astrophysics Data System (ADS)

Raghavan, Raghu; Brady, Martin

2011-10-01

Direct infusions into brain parenchyma of biological therapeutics for serious brain diseases have been, and are being, considered. However, individual brains, as well as distinct cytoarchitectural regions within brains, vary in their response to fluid flow and pressure. Further, the tissue responds dynamically to these stimuli, requiring a nonlinear treatment of equations that would describe fluid flow and drug transport in brain. We here report in detail on an individual-specific model and a comparison of its prediction with simulations for living porcine brains. Two critical features we introduced into our model—absent from previous ones, but requirements for any useful simulation—are the infusion-induced interstitial expansion and the backflow. These are significant determinants of the flow. Another feature of our treatment is the use of cross-property relations to obtain individual-specific parameters that are coefficients in the equations. The quantitative results are at least encouraging, showing a high fraction of overlap between the computed and measured volumes of distribution of a tracer molecule and are potentially clinically useful. Several improvements are called for; principally a treatment of the interstitial expansion more fundamentally based on poroelasticity and a better delineation of the diffusion tensor of a particle confined to the interstitial spaces.

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

PubMed Central

Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

2014-01-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin “halos.” Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2–3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6–15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin “halos,” with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that “halo” labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin “halo” labeling should not be used to demonstrate physiological bone interstitial fluid flow. PMID:15964255

Mapping bone interstitial fluid movement: displacement of ferritin tracer during histological processing.

PubMed

Ciani, Cesare; Doty, Stephen B; Fritton, Susannah P

2005-09-01

Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that "halo" labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin "halo" labeling should not be used to demonstrate physiological bone interstitial fluid flow.

Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient

PubMed Central

Dongaonkar, R. M.; Laine, G. A.; Stewart, R. H.

2011-01-01

Microvascular permeability to water is characterized by the microvascular filtration coefficient (Kf). Conventional gravimetric techniques to estimate Kf rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate Kf estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce Kf from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to Kf and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of Kf in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique. PMID:21346245

Probe for Sampling of Interstitial Fluid From Bone

NASA Technical Reports Server (NTRS)

Janle, Elsa M.

2004-01-01

An apparatus characterized as both a membrane probe and a bone ultrafiltration probe has been developed to enable in vivo sampling of interstitial fluid in bone. The probe makes it possible to measure the concentration of calcium and other constituents of the fluid that may be relevant to bone physiology. The probe could be especially helpful in experimental studies of microgravitational bone loss and of terrestrial bone-loss disease states, including osteoporosis. The probe can be implanted in the bone tissue of a living animal and can be used to extract samples of the interstitial bone fluid from time to time during a long-term study. The probe includes three 12-cm-long polyacrylonitrile fibers configured in a loop form and attached to polyurethane tubing [inside diameter 0.025 in. (0.64 mm), outside diameter 0.040 in. (1 mm)]; the attachment is made by use of a 1-cm-long connecting piece of polyurethane tubing [inside diameter 0.035 0.003 in. (0.89 0.08 mm), outside diameter 0.060 0.003 in. (1.52 0.08 mm)]. At the distal end, a 2-cm-long piece of polyurethane tubing of the same inner and outer diameters serves as a connector to a hub. A 1-cm long piece of expanded poly (tetrafluoroethylene) tubing over the joint between the fibers and the connecting tubing serves as a tissue-in-growth site.

Passenger fluid volumes measured before and after a prolonged commercial jet flight.

NASA Technical Reports Server (NTRS)

Johnson, P. C.; Carpentier, W. R.; Driscoll, T. B.; Lapinta, C. K.; Rummel, J. A.; Sawin, C. F.

1972-01-01

Interstitial and intracellular fluid volumes were calculated from measured plasma volume, extracellular volume and total body water of six subjects before and after a 24-hour commercial overseas flight. No change occurred in these spaces or in peripheral hematocrit or total serum protein concentration. The subjective feeling of dehydration and the actual swelling of the lower extremities characteristically found among passengers at the end of a long trip of this type seems to represent a shift in body fluids to the dependent portions of the body rather than water retention or a decrease in the intravascular water volume.

Separation of Solid Stress From Interstitial Fluid Pressure in Pancreas Cancer Correlates With Collagen Area Fraction.

PubMed

Nieskoski, Michael D; Marra, Kayla; Gunn, Jason R; Kanick, Stephen C; Doyley, Marvin M; Hasan, Tayyaba; Pereira, Stephen P; Stuart Trembly, B; Pogue, Brian W

2017-06-01

Elevated total tissue pressure (TTP) in pancreatic adenocarcinoma is often associated with stress applied by cellular proliferation and hydrated hyaluronic acid osmotic swelling; however, the causal roles of collagen in total tissue pressure have yet to be clearly measured. This study illustrates one direct correlation between total tissue pressure and increased deposition of collagen within the tissue matrix. This observation comes from a new modification to a conventional piezoelectric pressure catheter, used to independently separate and quantify total tissue pressure, solid stress (SS), and interstitial fluid pressure (IFP) within the same tumor location, thereby clarifying the relationship between these parameters. Additionally, total tissue pressure shows a direct correlation with verteporfin uptake, demonstrating the impediment of systemically delivered molecules with increased tissue hypertension.

Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

PubMed

Gromov, Pavel; Gromova, Irina

2016-01-01

Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.

An analytical model to predict interstitial lubrication of cartilage in migrating contact areas.

PubMed

Moore, A C; Burris, D L

2014-01-03

For nearly a century, articular cartilage has been known for its exceptional tribological properties. For nearly as long, there have been research efforts to elucidate the responsible mechanisms for application toward biomimetic bearing applications. It is now widely accepted that interstitial fluid pressurization is the primary mechanism responsible for the unusual lubrication and load bearing properties of cartilage. Although the biomechanics community has developed elegant mathematical theories describing the coupling of solid and fluid (biphasic) mechanics and its role in interstitial lubrication, quantitative gaps in our understanding of cartilage tribology have inhibited our ability to predict how tribological conditions and material properties impact tissue function. This paper presents an analytical model of the interstitial lubrication of biphasic materials under migrating contact conditions. Although finite element and other numerical models of cartilage mechanics exist, they typically neglect the important role of the collagen network and are limited to a specific set of input conditions, which limits general applicability. The simplified approach taken in this work aims to capture the broader underlying physics as a starting point for further model development. In agreement with existing literature, the model indicates that a large Peclet number, Pe, is necessary for effective interstitial lubrication. It also predicts that the tensile modulus must be large relative to the compressive modulus. This explains why hydrogels and other biphasic materials do not provide significant interstitial pressure under high Pe conditions. The model quantitatively agrees with in-situ measurements of interstitial load support and the results have interesting implications for tissue engineering and osteoarthritis problems. This paper suggests that a low tensile modulus (from chondromalacia or local collagen rupture after impact, for example) may disrupt interstitial pressurization, increase shear stresses, and activate a condition of progressive surface damage as a potential precursor of osteoarthritis. © 2013 Elsevier Ltd. All rights reserved.

Effect of tilting on blood pressure and interstitial fluid pressures of bluefish and smooth dogfish.

PubMed

Ogilvy, C S; DuBois, A B

1982-01-01

Tolerance of the circulatory system of fish for gravitational stress has not been measured previously. We examined this in bluefish (Pomatomus saltatrix) and smooth dogfish (Mustelus canis) by placing them horizontally on a V-board in air while their gills were perfused with aerated seawater, then tilting them head up for 0.5 h, and finally returning them to horizontal. Meanwhile, we recorded the blood pressure, pulse pressure, and heart rate in the ventral aorta, and interstitial fluid pressure in the head and tail. All four bluefish tolerated a 30 degrees tilt or even a 60 degrees tilt with little change in blood pressure or interstitial pressure in the anterior and posterior regions. All recovered afterward. However, in the seven dogfish examined, the posterior interstitial fluid pressure increased from 2.8 +/- 1.0 cmH2O before tilting to 11.8 +/- 3.3 cmH2O toward the end of a 30 degrees tilt lasting 30 min. The blood pressure decreased as the pulse pressure approached zero, showing that circulatory insufficiency had developed due to insufficient venous return to the heart. Most of the dogfish died within a few hours after the experiment. These findings are in keeping with the conclusion that the vasculature of bluefish has more rigidity, less permeability, and perhaps more compensatory tone than that of smooth dogfish. We speculate that bluefish may have evolved their circulatory tolerance for gravity as a cross-adaptation to the stresses imposed on the circulation by forward acceleration and by regional differences of transcutaneous pressure occurring during fast carangiform swimming.

Sphere based fluid systems

NASA Technical Reports Server (NTRS)

Elleman, Daniel D. (Inventor); Wang, Taylor G. (Inventor)

1989-01-01

Systems are described for using multiple closely-packed spheres. In one system for passing fluid, a multiplicity of spheres lie within a container, with all of the spheres having the same outside diameter and with the spheres being closely nested in one another to create multiple interstitial passages of a known size and configuration and smooth walls. The container has an inlet and outlet for passing fluid through the interstitial passages formed between the nested spheres. The small interstitial passages can be used to filter out material, especially biological material such as cells in a fluid, where the cells can be easily destroyed if passed across sharp edges. The outer surface of the spheres can contain a material that absorbs a constitutent in the flowing fluid, such as a particular contamination gas, or can contain a catalyst to chemically react the fluid passing therethrough, the use of multiple small spheres assuring a large area of contact of these surfaces of the spheres with the fluid. In a system for storing and releasing a fluid such as hydrogen as a fuel, the spheres can include a hollow shell containing the fluid to be stored, and located within a compressable container that can be compressed to break the shells and release the stored fluid.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

PubMed Central

Uemura, Mei; Suzuki, Toshinari; Yasuma, Taro; Sato, Toshiyuki; Morimoto, Aya; Hosoya, Samiko; Suminaka, Chihiro; Nakajima, Hiromu; Gabazza, Esteban C.; Takei, Yoshiyuki

2017-01-01

Background Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Methods Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. Results A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. Conclusion We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day. PMID:28868824

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients.

PubMed

Uemura, Mei; Yano, Yutaka; Suzuki, Toshinari; Yasuma, Taro; Sato, Toshiyuki; Morimoto, Aya; Hosoya, Samiko; Suminaka, Chihiro; Nakajima, Hiromu; Gabazza, Esteban C; Takei, Yoshiyuki

2017-08-01

Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference. Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity. We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day. Copyright © 2017 Korean Diabetes Association

The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

PubMed

Hitscherich, Kyle; Smith, Kyle; Cuoco, Joshua A; Ruvolo, Kathryn E; Mancini, Jayme D; Leheste, Joerg R; Torres, German

2016-03-01

The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

Mechanics of Fluid-Filled Interstitial Gaps. I. Modeling Gaps in a Compact Tissue.

PubMed

Parent, Serge E; Barua, Debanjan; Winklbauer, Rudolf

2017-08-22

Fluid-filled interstitial gaps are a common feature of compact tissues held together by cell-cell adhesion. Although such gaps can in principle be the result of weak, incomplete cell attachment, adhesion is usually too strong for this to occur. Using a mechanical model of tissue cohesion, we show that, instead, a combination of local prevention of cell adhesion at three-cell junctions by fluidlike extracellular material and a reduction of cortical tension at the gap surface are sufficient to generate stable gaps. The size and shape of these interstitial gaps depends on the mechanical tensions between cells and at gap surfaces, and on the difference between intracellular and interstitial pressures that is related to the volume of the interstitial fluid. As a consequence of the dependence on tension/tension ratios, the presence of gaps does not depend on the absolute strength of cell adhesion, and similar gaps are predicted to occur in tissues of widely differing cohesion. Tissue mechanical parameters can also vary within and between cells of a given tissue, generating asymmetrical gaps. Within limits, these can be approximated by symmetrical gaps. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The local pathology of interstitial edema: surface tension increases hydration potential in heat-damaged skin.

PubMed

McGee, Maria P; Morykwas, Michael J; Argenta, Louis C

2011-01-01

The local pathogenesis of interstitial edema in burns is incompletely understood. This ex vivo study investigates the forces mediating water-transfer in and out of heat-denatured interstitial matrix. Experimentally, full-thickness dermal samples are heated progressively to disrupt glycosaminoglycans, kill cells, and denature collagen under conditions that prevent water loss/gain; subsequently, a battery of complementary techniques including among others, high-resolution magnetic resonance imaging, equilibrium vapor pressure and osmotic stress are used to compare water-potential parameters of nonheated and heated dermis. The hydration potential (HP) determined by osmotic stress is a measure of the total water-potential defined empirically as the pressure at which no net water influx/efflux into/from the dermis is detected. Results show that after heat denaturation, the HP, the intensity of T2-weighed magnetic resonance images, and the vapor pressure increase indicating higher water activity and necessarily, smaller contributions from colloidosmotic forces to fluid influx in burned relative to healthy dermis. Concomitant increases in HP and in water activity implicate local changes in interfacial and metabolic energy as the source of excess fluid-transfer potential. These ex vivo findings also show that these additional forces contributing to abnormal fluid-transfer in burned skin develop independently of inflammatory and systemic hydrodynamic responses. © 2011 by the Wound Healing Society.

Effects of Arg-Gly-Asp sequence peptide and hyperosmolarity on the permeability of interstitial matrix and fenestrated endothelium in joints.

PubMed

Poli, A; Mason, R M; Levick, J R

2004-09-01

The aims were to assess the contribution of arg-gly-asp (RGD) mediated cell integrin-matrix bonds to interstitial hydraulic resistance and to fenestrated endothelial permeability in joints. Joint fluid is generated by filtration from fenestrated capillaries and drains through a fibronectin-rich synovial intercellular matrix. The role of parenchymal cell-matrix bonding in determining tissue hydraulic resistance is unknown. The knee cavity of anesthetized rabbits was infused with saline or the competitive hexapeptide blocker GRGDTP, with or without added osmotic stress (600 mosm saline). Intra-articular pressure Pj, net trans-synovial drainage rate s, and the permeation of Evans blue-labeled albumin (EVA) from plasma into the joint cavity were measured. GRGDTP increased the hydraulic conductance of the synovial drainage pathway, ds/dPj, by 71% (p =.02, paired t test, n = 6 animals). Synovial plasma EVA clearance (control 7.1 +/- 0.8 microL h-1, mean +/- SEM, n = 15) was unaffected by GRGDTP (7.0 +/- 2.3 microL h(-1), n = 6) or hyperosmolarity (4.9 +/- 1.5 microL h(-1), n = 8) but was increased by GRGDTP and hyperosmolarity together (15.9 +/- 4.8 microL h(-1), n = 5) (p =.01, ANOVA). Changes in dPj/dt evoked by GRGDTP plus hyperosmolarity, but neither alone, demonstrated increased microvascular filtration into the joint cavity (p <.001, ANOVA), as did changes in fluid absorption from the infusion system at fixed Pj. RGD-mediated bonds between the parenchymal cells and interstitial polymers reduce the interstitial hydraulic conductance by 42%. This helps to retain the lubricating fluid inside a joint cavity. RGD-mediated bonds also support the macromolecular barrier function of fenestrated endothelium, but in vivo this is evident only in stressed endothelium (cf. in vitro).

"Artificial lymphatic system": a new approach to reduce interstitial hypertension and increase blood flow, pH and pO2 in solid tumors.

PubMed

DiResta, G R; Lee, J; Healey, J H; Levchenko, A; Larson, S M; Arbit, E

2000-05-01

A mechanical drainage system, the "artificial lymphatic system" (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, P(E), reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p<0.05), especially in regions surrounding the drain, and BFR was significantly higher (p<0.05) following 25 and 45 min of aspiration, respectively; pH and pO2 profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO2, and pH and should enhance solid tumor chemo and radiation therapy.

Self-powered microneedle-based biosensors for pain-free high-accuracy measurement of glycaemia in interstitial fluid.

PubMed

Strambini, L M; Longo, A; Scarano, S; Prescimone, T; Palchetti, I; Minunni, M; Giannessi, D; Barillaro, G

2015-04-15

In this work a novel self-powered microneedle-based transdermal biosensor for pain-free high-accuracy real-time measurement of glycaemia in interstitial fluid (ISF) is reported. The proposed transdermal biosensor makes use of an array of silicon-dioxide hollow microneedles that are about one order of magnitude both smaller (borehole down to 4µm) and more densely-packed (up to 1×10(6)needles/cm(2)) than state-of-the-art microneedles used for biosensing so far. This allows self-powered (i.e. pump-free) uptake of ISF to be carried out with high efficacy and reliability in a few seconds (uptake rate up to 1µl/s) by exploiting capillarity in the microneedles. By coupling the microneedles operating under capillary-action with an enzymatic glucose biosensor integrated on the back-side of the needle-chip, glucose measurements are performed with high accuracy (±20% of the actual glucose level for 96% of measures) and reproducibility (coefficient of variation 8.56%) in real-time (30s) over the range 0-630mg/dl, thus significantly improving microneedle-based biosensor performance with respect to the state-of-the-art. Copyright © 2014 Elsevier B.V. All rights reserved.

Numerical Modeling of Interstitial Fluid Flow Coupled with Blood Flow through a Remodeled Solid Tumor Microvascular Network

PubMed Central

Soltani, M.; Chen, P.

2013-01-01

Modeling of interstitial fluid flow involves processes such as fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. To date, majority of microvascular flow modeling has been done at different levels and scales mostly on simple tumor shapes with their capillaries. However, with our proposed numerical model, more complex and realistic tumor shapes and capillary networks can be studied. Both blood flow through a capillary network, which is induced by a solid tumor, and fluid flow in tumor’s surrounding tissue are formulated. First, governing equations of angiogenesis are implemented to specify the different domains for the network and interstitium. Then, governing equations for flow modeling are introduced for different domains. The conservation laws for mass and momentum (including continuity equation, Darcy’s law for tissue, and simplified Navier–Stokes equation for blood flow through capillaries) are used for simulating interstitial and intravascular flows and Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. This is the first study of flow modeling in solid tumors to naturalistically couple intravascular and extravascular flow through a network. This network is generated by sprouting angiogenesis and consisting of one parent vessel connected to the network while taking into account the non-continuous behavior of blood, adaptability of capillary diameter to hemodynamics and metabolic stimuli, non-Newtonian blood flow, and phase separation of blood flow in capillary bifurcation. The incorporation of the outlined components beyond the previous models provides a more realistic prediction of interstitial fluid flow pattern in solid tumors and surrounding tissues. Results predict higher interstitial pressure, almost two times, for realistic model compared to the simplified model. PMID:23840579

Bone tissue engineering: the role of interstitial fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1994-01-01

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Measurement of net whole-body transcapillary fluid transport and effective vascular compliance in humans

NASA Technical Reports Server (NTRS)

Watenpaugh, D. E.; Gaffney, F. A.; Schneider, S. M. (Principal Investigator)

1998-01-01

BACKGROUND: Net whole-body transcapillary fluid transport (TFT) between the circulation and the interstitial (extravascular) space may be calculated as: IV - deltaPV - UV - IL, where IV=infused or ingested volume (when applicable), deltaPV = change in plasma volume, UV=urine volume, and IL=insensible loss. RESULTS: Infusion of 30 mL/kg isotonic saline over 25 minutes increased supine TFT from a basal capillary reabsorption of -106+/-24 mL/h (mean+/-SE) to a net filtration of 1,229+/-124 mL/h. One hour after infusion, reabsorption of -236+/-102 mL/h was seen, and control reabsorption levels returned by 3 hours. Four hours of 30 mm Hg lower body negative pressure (LBNP) elicited no net TFT, probably because of upper body reabsorptive compensation for lower body capillary filtration. When ingestion of 1 L of isotonic saline accompanied LBNP, filtration of 145+/-10 mL/h occurred. Reabsorption of extravascular fluid into the circulation always followed LBNP. CONCLUSION: Application of this technique could aid understanding of physiologic conditions, experimental interventions, disease states, and therapies that cause or are influenced by fluid shifts between intravascular and interstitial compartments.

Hybrid microneedles devices for diagnostic and therapeutic applications: fabrication and preliminary results

NASA Astrophysics Data System (ADS)

Dardano, P.; Caliò, A.; Politi, J.; Di Palma, V.; Bevilacqua, M. F.; Rea, I.; Casalino, M.; Di Matteo, A.; Rendina, I.; De Stefano, L.

2015-06-01

Microneedles are newly developed biomedical devices, whose advantages are mainly in the non-invasiveness, discretion and versatility of use both as diagnostics and as therapeutics tool. In fact, they can be used both for drugs delivery in the interstitial fluids and for the analysis of the interstitial fluid. In this work we present the preliminary results for two devices based on micro needles in PolyEthylene (Glycol). The first for the drugs delivery includes a membrane whose optical reflected wavelength is related to the concentration of drug. Here, we present our preliminary result in diffusion of drugs between the membrane and the microneedles. The second device is gold coated and it works as electrode for the electrochemical detection of species in the interstitial fluid. A preliminary result in detection of glucose will be shown.

Non-invasive imaging of barriers to drug delivery in tumors.

PubMed

Hassid, Yaron; Eyal, Erez; Margalit, Raanan; Furman-Haran, Edna; Degani, Hadassa

2008-08-01

Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances. Sequential images are recorded during continuous infusion of a Gd-based contrast agent and analyzed according to a new physiological model, yielding maps of microvascular transfer constants, as well as outward convective interstitial transfer constants and steady state interstitial contrast agent concentrations both reflecting IFP distribution. We further demonstrated in non small cell human lung cancer xenografts the capability of our techniques to monitor in vivo collagenase induced increase in contrast agent delivery as a result of decreased IFP. These techniques can be applied to test drugs that affect angiogenesis and modulate interstitial fluid pressure and has the potential to be extended to cancer patients for assessing resistance to drug delivery.

Non-Invasive Imaging of Barriers to Drug Delivery in Tumors

PubMed Central

Hassid, Yaron; Eyal, Erez; Margalit, Raanan; Furman-Haran, Edna; Degani, Hadassa

2011-01-01

Solid tumors often develop high interstitial fluid pressure (IFP) as a result of increased water leakage and impaired lymphatic drainage, as well as changes in the extracellular matrix composition and elasticity. This high fluid pressure forms a barrier to drug delivery and hence, resistance to therapy. We have developed techniques based on contrast enhanced magnetic resonance imaging for mapping in tumors the vascular and transport parameters determining the delivery efficiency of blood borne substances. Sequential images are recorded during continuous infusion of a Gd-based contrast agent and analyzed according to a new physiological model, yielding maps of microvascular transfer constants, as well as outward convective interstitial transfer constants and steady state interstitial contrast agent concentrations both reflecting IFP distribution. We further demonstrated in non small cell human lung cancer xenografts the capability of our techniques to monitor in vivo collagenase induced increase in contrast agent delivery as a result of decreased IFP. These techniques can be applied to test drugs that affect angiogenesis and modulate interstitial fluid pressure and has the potential to be extended to cancer patients for assessing resistance to drug delivery. PMID:18638494

Interstitial hydraulic conductivity and interstitial fluid pressure for avascular or poorly vascularized tumors.

PubMed

Liu, L J; Schlesinger, M

2015-09-07

A correct description of the hydraulic conductivity is essential for determining the actual tumor interstitial fluid pressure (TIFP) distribution. Traditionally, it has been assumed that the hydraulic conductivities both in a tumor and normal tissue are constant, and that a tumor has a much larger interstitial hydraulic conductivity than normal tissue. The abrupt transition of the hydraulic conductivity at the tumor surface leads to non-physical results (the hydraulic conductivity and the slope of the TIFP are not continuous at tumor surface). For the sake of simplicity and the need to represent reality, we focus our analysis on avascular or poorly vascularized tumors, which have a necrosis that is mostly in the center and vascularization that is mostly on the periphery. We suggest that there is an intermediary region between the tumor surface and normal tissue. Through this region, the interstitium (including the structure and composition of solid components and interstitial fluid) transitions from tumor to normal tissue. This process also causes the hydraulic conductivity to do the same. We introduce a continuous variation of the hydraulic conductivity, and show that the interstitial hydraulic conductivity in the intermediary region should be monotonically increasing up to the value of hydraulic conductivity in the normal tissue in order for the model to correspond to the actual TIFP distribution. The value of the hydraulic conductivity at the tumor surface should be the lowest in value. Copyright © 2015 Elsevier Ltd. All rights reserved.

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy

PubMed Central

Winslow, Timothy B.; Eranki, Annu; Ullas, Soumya; Singh, Anurag K.; Repasky, Elizabeth A.; Sen, Arindam

2015-01-01

Purpose The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. Materials and methods SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Results Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Conclusions Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy. PMID:25986432

A pilot study of the effects of mild systemic heating on human head and neck tumour xenografts: Analysis of tumour perfusion, interstitial fluid pressure, hypoxia and efficacy of radiation therapy.

PubMed

Winslow, Timothy B; Eranki, Annu; Ullas, Soumya; Singh, Anurag K; Repasky, Elizabeth A; Sen, Arindam

2015-01-01

The tumour microenvironment is frequently hypoxic, poorly perfused, and exhibits abnormally high interstitial fluid pressure. These factors can significantly reduce efficacy of chemo and radiation therapies. The present study aims to determine whether mild systemic heating alters these parameters and improves response to radiation in human head and neck tumour xenografts in SCID mice. SCID mice were injected with FaDu cells (a human head and neck carcinoma cell line), or implanted with a resected patient head and neck squamous cell carcinoma grown as a xenograft, followed by mild systemic heating. Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h. Interstitial fluid pressure (IFP), hypoxia and relative tumour perfusion in the tumours were measured at 2 and 24 h post-heating. Tumour vessel perfusion was measured 24 h post-heating, coinciding with the first dose of fractionated radiotherapy. Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models. Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment. Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice. Mild systemic heating can significantly alter the tumour microenvironment of human head and neck tumour xenograft models, decreasing IFP and hypoxia while increasing microvascular perfusion. Collectively, these effects could be responsible for the improved response to radiotherapy.

Antisecretory Factor-mediated Inhibition of Cell Volume Dynamics Produces Anti-tumor Activity in Glioblastoma. | Office of Cancer Genomics

Cancer.gov

Interstitial fluid pressure (IFP) presents a barrier to drug uptake in solid tumors, including the aggressive primary brain tumor glioblastoma multiforme (GBM). It remains unclear how fluid dynamics impacts tumor progression and can be targeted therapeutically. To address this issue, a novel telemetry-based approach was developed to measure changes in IFP during progression of GBM xenografts. Antisecretory factor (AF) is an endogenous protein that displays anti-secretory effects in animals and patients.

Particle-bearing currents in uniform density and two-layer fluids

NASA Astrophysics Data System (ADS)

Sutherland, Bruce R.; Gingras, Murray K.; Knudson, Calla; Steverango, Luke; Surma, Christopher

2018-02-01

Lock-release gravity current experiments are performed to examine the evolution of a particle bearing flow that propagates either in a uniform-density fluid or in a two-layer fluid. In all cases, the current is composed of fresh water plus micrometer-scale particles, the ambient fluid is saline, and the current advances initially either over the surface as a hypopycnal current or at the interface of the two-layer fluid as a mesopycnal current. In most cases the tank is tilted so that the ambient fluid becomes deeper with distance from the lock. For hypopycnal currents advancing in a uniform density fluid, the current typically slows as particles rain out of the current. While the loss of particles alone from the current should increase the current's buoyancy and speed, in practice the current's speed decreases because the particles carry with them interstitial fluid from the current. Meanwhile, rather than settling on the sloping bottom of the tank, the particles form a hyperpycnal (turbidity) current that advances until enough particles rain out that the relatively less dense interstitial fluid returns to the surface, carrying some particles back upward. When a hypopycnal current runs over the surface of a two-layer fluid, the particles that rain out temporarily halt their descent as they reach the interface, eventually passing through it and again forming a hyperpycnal current. Dramatically, a mesopycnal current in a two-layer fluid first advances along the interface and then reverses direction as particles rain out below and fresh interstitial fluid rises above.

Microstructures of Randall's plaques and their interfaces with calcium oxalate monohydrate kidney stones reflect underlying mineral precipitation mechanisms.

PubMed

Sethmann, Ingo; Wendt-Nordahl, Gunnar; Knoll, Thomas; Enzmann, Frieder; Simon, Ludwig; Kleebe, Hans-Joachim

2017-06-01

Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.

Determination of glucose in interstitial fluid by surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Huang, Fuxiang; Liu, Jin; Yu, Haixia; Zhang, Zengfu; Li, Dachao; Xu, Kexin

2008-02-01

The concentration of glucose in interstitial fluid determined by using the surface plasmon resonance (SPR) biosensor with chemical bonding D-Galactose/D-Glucose Binding Protein (GGBP) is proposed in this paper. D-Galactose/D-Glucose Binding Protein (GGBP), a kind of protein which has the ability to absorb the glucose specifically, is immobilized on the gold film of the SPR sensor to improve the sensitivity of glucose detecting. The GGBPs mutated at different points have different association abilities with glucose, which bring different measurement range and precision. So the selection of proteins is a critical problem of the determination of glucose by using SPR biosensor. Using different mutated GGBPs, the samples with different concentrations of glucose are measured in the experiment, and the prediction error and precision are discussed. Furthermore, the light intensity of sensor is instable, so the baseline of SPR responses is tracked and adjusted accordingly using the methods - fixing points and fixing areas' ratio. The experiment results show that GGBPs mutated at different points have its corresponding working curves and different measurement precision. In conclusion, the study is significant for the application of SPR biosensor to the minimally invasive diabetes testing and other detection of human body components.

Numerical modeling of fluid and oxygen exchanges through microcirculation for the assessment of microcirculation alterations caused by type 2 diabetes.

PubMed

Tang, Yuanliang; He, Ying

2018-05-01

Type 2 diabetes mellitus (DM2) is frequently accompanied by microcirculation complications, including structural and functional alterations, which may have serious effects on substance exchanges between blood and interstitial tissue and the health of organs. In this paper, we aim to study the influence of microcirculation alterations in DM2 patients on fluid and oxygen exchanges through a model analysis. A fluid flow and oxygen transport model were developed by considering the interplay between blood in capillary network and interstitial tissue. The two regions were separately represented by 1D network model and 3D volume model, and the immersed boundary method (IBM) was adopted to solve fluid and mass transfer between these two regions. By using the model, the steady flow field and the distributions of oxygen in capillary network and surrounding tissue were firstly simulated. In the interstitial volume, fluid pressure and oxygen tension decreased with the increase of distance from the network; in the network, oxygen tension in blood plasma dropped from 100 mm Hg at the entrance to about 40 mm Hg at the exit. We further tested several structural and functional disorders related to diabetic pathological conditions. Simulated results show that the impaired connectivity of the network could result in poor robustness in maintaining blood flow and perfused surface; under high fluid permeability conditions of capillary walls, the pressure gradient was much larger around the capillary bed, and this alteration led to a saturation level of the interstitial pressure when lymphatic flow drainage can't work effectively; the variations in network connectivity and permeability of capillary wall also had unfavorable influence on oxygen distributions in interstitial tissue. In addition, when the oxygen releasing capacity of hemoglobin was confined by glycosylated hemoglobin (HbA1) in the case of diabetes, the plasma could not be complemented with adequate oxygen and thus the hypoxic tissue range will be extended. This study illustrates that when microcirculation disturbances, including the structure of capillary network, the wall osmosis property and the capacity of blood binding oxygen occur in DM2, some negative impacts are raised on microvascular hemodynamics and metabolism circumstance of interstitial tissue. Copyright © 2018 Elsevier Inc. All rights reserved.

Mapping the spatiotemporal evolution of solute transport in articular cartilage explants reveals how cartilage recovers fluid within the contact area during sliding.

PubMed

Graham, Brian T; Moore, Axel C; Burris, David L; Price, Christopher

2018-04-11

The interstitial fluid within articular cartilage shields the matrix from mechanical stresses, reduces friction and wear, enables biochemical processes, and transports solutes into and out of the avascular extracellular matrix. The balanced competition between fluid exudation and recovery under load is thus critical to the mechanical and biological functions of the tissue. We recently discovered that sliding alone can induce rapid solute transport into buried cartilage contact areas via a phenomenon termed tribological rehydration. In this study, we use in situ confocal microscopy measurements to track the spatiotemporal propagation of a small neutral solute into the buried contact area to clarify the fluid mechanics underlying the tribological rehydration phenomenon. Sliding experiments were interrupted by periodic static loading to enable scanning of the entire contact area. Spatiotemporal patterns of solute transport combined with tribological data suggested pressure driven flow through the extracellular matrix from the contact periphery rather than into the surface via a fluid film. Interestingly, these testing interruptions also revealed dynamic, repeatable and history-independent fluid loss and recovery processes consistent with those observed in vivo. Unlike the migrating contact area, which preserves hydration by moving faster than interstitial fluid can flow, our results demonstrate that the stationary contact area can maintain and actively recover hydration through a dynamic competition between load-induced exudation and sliding-induced recovery. The results demonstrate that sliding contributes to the recovery of fluid and solutes by cartilage within the contact area while clarifying the means by which it occurs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Therapeutic Effects of Human Amniotic Fluid-Derived Stem Cells on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

PubMed Central

Yin, Zhongcheng; Zhou, Xudong; Li, Xiaoju; Xiao, Aiguo

2013-01-01

Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis. PMID:23724119

Prediction of oxygen distribution in aortic valve leaflet considering diffusion and convection.

PubMed

Wang, Ling; Korossis, Sotirios; Fisher, John; Ingham, Eileen; Jin, Zhongmin

2011-07-01

Oxygen supply and transport is an important consideration in the development of tissue engineered constructs. Previous studies from our group have focused on the effect of tissue thickness on the oxygen diffusion within a three-dimensional aortic valve leaflet model, and highlighted the necessity for additional transport mechanisms such as oxygen convection. The aims of this study were to investigate the effect of interstitial fluid flow within the aortic valve leaflet, induced by the cyclic loading of the leaflet, on oxygen transport. Indentation testing and finite element modelings were employed to derive the biphasic properties of the leaflet tissue. The biphasic properties were subsequently used in the computational modeling of oxygen convection in the leaflet, which was based on the effective interstitial fluid velocity and the tissue deformation. Subsequently, the oxygen profile was predicted within the valve leaflet model by solving the diffusion and convection equation simultaneously utilizing the finite difference method. The compression modulus (E) and hydraulic permeability were determined by adapting a finite element model to the experimental indentation test on valvular tissue, E = 0.05MPa, and k =2.0 mm4/Ns. Finite element model of oxygen convection in valvular tissue incorporating the predicted biphasic properties was developed and the interstitial fluid flow rate was calculated falling in range of 0.025-0.25 mm/s depending on the tissue depth. Oxygen distribution within valvular tissue was predicted using one-dimensional oxygen diffusion model taking into consider the interstitial fluid effect. It was found that convection did enhance the oxygen transport in valvular tissue by up to 68% increase in the minimum oxygen tension within the tissue, depending on the strain level of the tissue as reaction of the magnitude and frequencies of the cardiac loading. The effective interstitial fluid velocity was found to play an important role in enhancing the oxygen transport within the valve leaflet. Such an understanding is important in the development of valvular tissue engineered constructs.

The Emerging Relationship Between Interstitial Fluid-Cerebrospinal Fluid Exchange, Amyloid-β, and Sleep.

PubMed

Boespflug, Erin L; Iliff, Jeffrey J

2018-02-15

Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Physiology of Fluid and Electrolyte Responses During Inactivity: Water Immersion and Bed Rest

NASA Technical Reports Server (NTRS)

Greenleaf, John E.

1984-01-01

This manuscript emphasizes the physiology of fluid-electrolyte-hormonal responses during the prolonged inactivity of bed rest and water immersion. An understanding of the total mechanism of adaptation (deconditioning) should provide more insight into the conditioning process. Findings that need to be confirmed during bed rest and immersion are: (1) the volume and tissues of origin of fluid shifted to the thorax and head; (2) interstitial fluid pressure changes in muscle and subcutaneous tissue, particularly during immersion; and (3) the composition of the incoming presumably interstitial fluid that contributes to the early hypervolemia. Better resolution of the time course and source of the diuretic fluid is needed. Important data will be forthcoming when hypotheses are tested involving the probable action of the emerging diuretic and natriuretic hormones, between themselves and among vasopressin and aldosterone, on diuresis and blood pressure control.

The hydraulic permeability of blood clots as a function of fibrin and platelet density.

PubMed

Wufsus, A R; Macera, N E; Neeves, K B

2013-04-16

Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02-0.54 had permeabilities of 1.2 × 10(-1)-1.5 × 10(-4)μm(2). Platelet-rich clots with a platelet volume fraction of 0.01-0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10(-2)-1.5 × 10(-5)μm(2). The permeability of fibrin gels and of clots with platelet volume fraction of <0.2 were modeled as an array of disordered cylinders with uniform diameters. Clots with a platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Hydraulic Permeability of Blood Clots as a Function of Fibrin and Platelet Density

PubMed Central

Wufsus, A.R.; Macera, N.E.; Neeves, K.B.

2013-01-01

Interstitial fluid flow within blood clots is a biophysical mechanism that regulates clot growth and dissolution. Assuming that a clot can be modeled as a porous medium, the physical property that dictates interstitial fluid flow is the hydraulic permeability. The objective of this study was to bound the possible values of the hydraulic permeability in clots formed in vivo and present relationships that can be used to estimate clot permeability as a function of composition. A series of clots with known densities of fibrin and platelets, the two major components of a clot, were formed under static conditions. The permeability was calculated by measuring the interstitial fluid velocity through the clots at a constant pressure gradient. Fibrin gels formed with a fiber volume fraction of 0.02–0.54 had permeabilities of 1.2 × 10−1–1.5 × 10−4μm2. Platelet-rich clots with a platelet volume fraction of 0.01–0.61 and a fibrin volume fraction of 0.03 had permeabilities over a range of 1.1 × 10−2–1.5 × 10−5μm2. The permeability of fibrin gels and of clots with platelet volume fraction of <0.2 were modeled as an array of disordered cylinders with uniform diameters. Clots with a platelet volume fraction of >0.2 were modeled as a Brinkman medium of coarse solids (platelets) embedded in a mesh of fine fibers (fibrin). Our data suggest that the permeability of clots formed in vivo can vary by up to five orders of magnitude, with pore sizes that range from 4 to 350 nm. These findings have important implications for the transport of coagulation zymogens/enzymes in the interstitial spaces during clot formation, as well as the design of fibrinolytic drug delivery strategies. PMID:23601328

Non-invasive, transdermal, path-selective and specific glucose monitoring via a graphene-based platform

NASA Astrophysics Data System (ADS)

Lipani, Luca; Dupont, Bertrand G. R.; Doungmene, Floriant; Marken, Frank; Tyrrell, Rex M.; Guy, Richard H.; Ilie, Adelina

2018-06-01

Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and `quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.

Granular Material Flows with Interstitial Fluid Effects

NASA Technical Reports Server (NTRS)

Hunt, Melany L.; Brennen, Christopher E.

2004-01-01

The research focused on experimental measurements of the rheological properties of liquid-solid and granular flows. In these flows, the viscous effects of the interstitial fluid, the inertia of the fluid and particles, and the collisional interactions of the particles may all contribute to the flow mechanics. These multiphase flows include industrial problems such as coal slurry pipelines, hydraulic fracturing processes, fluidized beds, mining and milling operation, abrasive water jet machining, and polishing and surface erosion technologies. In addition, there are a wide range of geophysical flows such as debris flows, landslides and sediment transport. In extraterrestrial applications, the study of transport of particulate materials is fundamental to the mining and processing of lunar and Martian soils and the transport of atmospheric dust (National Research Council 2000). The recent images from Mars Global Surveyor spacecraft dramatically depict the complex sand and dust flows on Mars, including dune formation and dust avalanches on the slip-face of dune surfaces. These Aeolian features involve a complex interaction of the prevailing winds and deposition or erosion of the sediment layer; these features make a good test bed for the verification of global circulation models of the Martian atmosphere.

Feeding-dependent activation of enteric cells and sensory neurons by lymphatic fluid: evidence for a neurolymphocrine system

PubMed Central

Poole, Daniel P.; Lee, Mike; Tso, Patrick; Bunnett, Nigel W.; Yo, Sek Jin; Lieu, TinaMarie; Shiu, Amy; Wang, Jen-Chywan; Nomura, Daniel K.

2014-01-01

Lymphatic fluid is a plasma filtrate that can be viewed as having biological activity through the passive accumulation of molecules from the interstitial fluid. The possibility that lymphatic fluid is part of an active self-contained signaling process that parallels the endocrine system, through the activation of G-protein coupled receptors (GPCR), has remained unexplored. We show that the GPCR lysophosphatidic acid 5 (LPA5) is found in sensory nerve fibers expressing calcitonin gene-related peptide (CGRP) that innervate the lumen of lymphatic lacteals and enteric nerves. Using LPA5 as a model for nutrient-responsive GPCRs present on sensory nerves, we demonstrate that dietary protein hydrolysate (peptone) can induce c-Fos expression in enterocytes and nerves that express LPA5. Mesenteric lymphatic fluid (MLF) mobilizes intracellular calcium in cell models expressing LPA5 upon feeding in a time- and dose-dependent manner. Primary cultured neurons of the dorsal root ganglia expressing CGRP are activated by MLF, which is enhanced upon LPA5 overexpression. Activation is independent of the known LPA5 agonists, lysophosphatidic acid and farnesyl pyrophosphate. These data bring forth a pathway for the direct stimulation of sensory nerves by luminal contents and interstitial fluid. Thus, by activating LPA5 on sensory nerves, MLF provides a means for known and yet to be identified constituents of the interstitial fluid to act as signals to comprise a “neurolymphocrine” system. PMID:24578341

Assessment and Management of Volume Overload and Congestion in Chronic Heart Failure: Can Measuring Blood Volume Provide New Insights?

PubMed

Miller, Wayne L

2017-01-01

Volume overload and fluid congestion remain primary clinical challenges in the assessment and management of patients with chronic heart failure (HF). The pathophysiology of volume regulation is complex, and the simple concept of passive intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to the central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in chronic HF. The quantitative assessment of intravascular volume is an effective tool to help guide individualized, appropriate therapy. Not all volume overload is the same, and the measurement of intravascular volume identifies heterogeneity to guide tailored therapy.

Is postural tremor size controlled by interstitial potassium concentration in muscle?

PubMed Central

Lakie, M; Hayes, N; Combes, N; Langford, N

2004-01-01

Objectives: To determine whether factors associated with postural tremor operate by altering muscle interstitial K+. Methods: An experimental approach was used to investigate the effects of procedures designed to increase or decrease interstitial K+. Postural physiological tremor was measured by conventional means. Brief periods of ischaemic muscle activity were used to increase muscle interstitial K+. Infusion of the ß2 agonist terbutaline was used to decrease plasma (and interstitial) K+. Blood samples were taken for the determination of plasma K+. Results: Ischaemia rapidly reduced tremor size, but only when the muscle was active. The ß2 agonist produced a slow and progressive rise in tremor size that was almost exactly mirrored by a slow and progressive decrease in plasma K+. Conclusions: Ischaemic reduction of postural tremor has been attributed to effects on muscle spindles or an unexplained effect on muscle. This study showed that ischaemia did not reduce tremor size unless there was accompanying muscular activity. An accumulation of K+ in the interstitium of the ischaemic active muscle may blunt the response of the muscle and reduce its fusion frequency, so that the force output becomes less pulsatile and tremor size decreases. When a ß2 agonist is infused, the rise in tremor mirrors the resultant decrease in plasma K+. Decreased plasma K+ reduces interstitial K+ concentration and may produce greater muscular force fluctuation (more tremor). Many other factors that affect postural tremor size may exert their effect by altering plasma K+ concentration, thereby changing the concentration of K+ in the interstitial fluid. PMID:15201362

Interstitial flow influences direction of tumor cell migration through competing mechanisms

PubMed Central

Polacheck, William J.; Charest, Joseph L.; Kamm, Roger D.

2011-01-01

Interstitial flow is the convective transport of fluid through tissue extracellular matrix. This creeping fluid flow has been shown to affect the morphology and migration of cells such as fibroblasts, cancer cells, endothelial cells, and mesenchymal stem cells. A microfluidic cell culture system was designed to apply stable pressure gradients and fluid flow and allow direct visualization of transient responses of cells seeded in a 3D collagen type I scaffold. We used this system to examine the effects of interstitial flow on cancer cell morphology and migration and to extend previous studies showing that interstitial flow increases the metastatic potential of MDA-MB-435S melanoma cells [Shields J, et al. (2007) Cancer Cell 11:526–538]. Using a breast carcinoma line (MDA-MB-231) we also observed cell migration along streamlines in the presence of flow; however, we further demonstrated that the strength of the flow as well as the cell density determined directional bias of migration along the streamline. In particular, we found that cells either at high seeding density or with the CCR-7 receptor inhibited migration against, rather than with the flow. We provide further evidence that CCR7-dependent autologous chemotaxis is the mechanism that leads to migration with the flow, but also demonstrate a competing CCR7-independent mechanism that causes migration against the flow. Data from experiments investigating the effects of cell concentration, interstitial flow rate, receptor activity, and focal adhesion kinase phosphorylation support our hypothesis that the competing stimulus is integrin mediated. This mechanism may play an important role in development of metastatic disease. PMID:21690404

Translocation pathways for inhaled asbestos fibers

PubMed Central

Miserocchi, G; Sancini, G; Mantegazza, F; Chiappino, Gerolamo

2008-01-01

We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption) and hydraulic (interstitial pressure is subatmospheric) pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation) wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation). Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots) reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow) and in the liver (reflecting high microvascular permeability) while it is relatively low in the brain (due to low permeability of blood-brain barrier). Ultrafine fibers (length < 5 μm, diameter < 0.25 μm) can travel larger distances due to low steric hindrance (in mesothelioma about 90% of fibers are ultrafine). Fibers translocation is a slow process developing over decades of life: it is aided by high biopersistence, by inflammation-induced increase in permeability, by low steric hindrance and by fibers motion pattern at low Reynolds numbers; it is hindered by fibrosis that increases interstitial flow resistances. PMID:18218073

Modeling viscous dissipation during vocal fold contact: the influence of tissue viscosity and thickness with implications for hydration.

PubMed

Erath, Byron D; Zañartu, Matías; Peterson, Sean D

2017-06-01

The mechanics of vocal fold contact during phonation is known to play a crucial role in both normal and pathological speech production, though the underlying physics is not well understood. Herein, a viscoelastic model of the stresses during vocal fold contact is developed. This model assumes the cover to be a poroelastic structure wherein interstitial fluid translocates in response to mechanical squeezing. The maximum interstitial fluid pressure is found to generally increase with decreasing viscous dissipation and/or decreasing tissue elasticity. A global minimum in the total contact stress, comprising interstitial fluid pressure and elastic stress in the tissue, is observed over the studied dimensionless parameter range. Interestingly, physiologically reasonable estimates for the governing parameters fall within this global minimum region. The model is validated against prior experimental and computational work, wherein the predicted contact stress magnitude and impact duration agree well with published results. Lastly, observations of the potential relationship between vocal fold hydration and increased risk of tissue damage are discussed based upon model predictions of stress as functions of cover layer thickness and viscosity.

Dissolution kinetics and biodurability of tremolite particles in mimicked lung fluids: Effect of citrate and oxalate

NASA Astrophysics Data System (ADS)

Rozalen, Marisa; Ramos, M. Elena; Huertas, F. Javier; Fiore, Saverio; Gervilla, Fernando

2013-11-01

The effect of citrate and oxalate on tremolite dissolution rate was measured at 37 °C in non-stirred flow-through reactors, using modified Gamble's solutions at pH 4 (macrophages), 7.4 (interstitial fluids) and 5.5 (intermediate check point) containing 0, 0.15, 1.5 and 15 mmol L-1 of citrate or oxalate. The dissolution rates calculated from Si concentration in the output solutions without organic ligands depend on pH, decreasing when the pH increases from -13.00 (pH 4) to -13.35 (pH 7.4) mol g-1 s-1 and following a proton-promoted mechanism. The presence of both ligands enhances dissolution rates at every pH, increasing this effect when the ligand concentration increases. Citrate produces a stronger effect as a catalyst than oxalate, mainly at more acidic pHs and enhances dissolution rates until 20 times for solutions with 15 mmol L-1 citrate. However, at pH 7.4 the effect is lighter and oxalate solutions (15 mmol L-1) only enhances dissolution rates eight times respect to free organic ligand solutions. Dissolution is promoted by the attack to protons and organic ligands to the tremolite surface. Magnesium speciation in oxalate and citrate solutions shows that Mg citrate complexes are more effective than oxalate ones during the alteration of tremolite in magrophages, but this tendency is the opposite for interstitial fluids, being oxalate magnesium complexes stronger. The biodurability estimations show that the destruction of the fibers is faster in acidic conditions (macrophages) than in the neutral solutions (interstitial fluid). At pH 4, both ligands oxalate and citrate reduce the residence time of the fibers with respect to that calculated in absence of ligands. Nevertheless, at pH 7.4 the presence of ligands does not reduce significantly the lifetime of the fibers.

Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

PubMed

Bodenlenz, M; Ellmerer, M; Schaupp, L; Jacobsen, L V; Plank, J; Brunner, G A; Wutte, A; Aigner, B; Mautner, S I; Pieber, T R

2015-12-01

To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. © 2015 John Wiley & Sons Ltd.

Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration.

PubMed

Moscardó, Vanessa; Bondia, Jorge; Ampudia-Blasco, Francisco J; Fanelli, Carmine G; Lucidi, Paola; Rossetti, Paolo

2018-04-01

Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus. Eleven subjects with type 1 diabetes (age 36.5 ± 9.1 years, HbA 1c 7.9 ± 0.4% [62.8 ± 2.02 mmol/mol]; mean ± standard deviation) were evaluated under hyperinsulinemic euglycemia and hypoglycemia. Each subject underwent two randomized crossover clamps with either a primed 0.3 (low insulin) or 1 mU/(kg·min) (high insulin) insulin infusion. The raw CGM signal was normalized with median preclamp values to obtain a standardized measure of the interstitial glucose (IG) concentration before statistical analysis. The mean PI concentration was greater in high insulin studies (HISs) versus low insulin studies (LISs) (412.89 ± 13.63 vs. 177.22 ± 10.05 pmol/L). During hypoglycemia, glucagon, adrenaline, free fatty acids, glycerol, and beta-OH-butyrate were higher in the LIS (P < 0.0001). Likewise, the IG concentration was significantly different (P < 0.0001). This was due to lower IG concentration than plasma glucose (PG) concentration during the euglycemic hyperinsulinemic phases in the HIS. In contrast, no difference was observed during hypoglycemia. This was the result of an unchanged PG/IG gradient during the entire LIS, while in the HIS, this gradient increased during the hyperinsulinemic euglycemia phase. Both PI levels and hypoglycemia affect the relationship between IG and PG concentration. ClinicalTrials.gov Identifier: NCT01714895.

Fluid compartment and renal function alterations in the rat during 7 and 14 day head down tilt

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1991-01-01

Exposure to conditions of microgravity for any extended duration can modify the distribution of fluid within the vascular and interstitial spaces, and eventually intracellular volume. Whether the redistribution of fluid and resetting of volume homeostasis mechanisms is appropriate for the long term environmental requirements of the body in microgravity remains to be fully defined. The event that initiates the change in fluid volume homeostasis is the cephalad movement of fluid which potentially triggers volume sensors and stretch receptors (atrial stretch with the resulting release of atrial natriuretic peptide) and suppresses adrenergic activity via the carotid and aortic arch baroreceptors. All these events act in concert to reset blood and interstitial volume to new levels, which in turn modify the renin-angiotensin system. All these factors have an influence on the kidney, the end organ for fluid volume control. How the fluid compartment volume changes interrelate with alterations in renal functions under conditions of simulated microgravity is the focus of the present investigation which utilizes 25-30 deg head-down tilt in the rat.

Optical microsensor for continuous glucose measurements in interstitial fluid

NASA Astrophysics Data System (ADS)

Olesberg, Jonathon T.; Cao, Chuanshun; Yager, Jeffrey R.; Prineas, John P.; Coretsopoulos, Chris; Arnold, Mark A.; Olafsen, Linda J.; Santilli, Michael

2006-02-01

Tight control of blood glucose levels has been shown to dramatically reduce the long-term complications of diabetes. Current invasive technology for monitoring glucose levels is effective but underutilized by people with diabetes because of the pain of repeated finger-sticks, the inconvenience of handling samples of blood, and the cost of reagent strips. A continuous glucose sensor coupled with an insulin delivery system could provide closed-loop glucose control without the need for discrete sampling or user intervention. We describe an optical glucose microsensor based on absorption spectroscopy in interstitial fluid that can potentially be implanted to provide continuous glucose readings. Light from a GaInAsSb LED in the 2.2-2.4 μm wavelength range is passed through a sample of interstitial fluid and a linear variable filter before being detected by an uncooled, 32-element GaInAsSb detector array. Spectral resolution is provided by the linear variable filter, which has a 10 nm band pass and a center wavelength that varies from 2.18-2.38 μm (4600-4200 cm -1) over the length of the detector array. The sensor assembly is a monolithic design requiring no coupling optics. In the present system, the LED running with 100 mA of drive current delivers 20 nW of power to each of the detector pixels, which have a noise-equivalent-power of 3 pW/Hz 1/2. This is sufficient to provide a signal-to-noise ratio of 4500 Hz 1/2 under detector-noise limited conditions. This signal-to-noise ratio corresponds to a spectral noise level less than 10 μAU for a five minute integration, which should be sufficient for sub-millimolar glucose detection.

Physiological water model development

NASA Technical Reports Server (NTRS)

Doty, Susan

1993-01-01

The water of the human body can be categorized as existing in two main compartments: intracellular water and extracellular water. The intracellular water consists of all the water within the cells and constitutes over half of the total body water. Since red blood cells are surrounded by plasma, and all other cells are surrounded by interstitial fluid, the intracellular compartment has been subdivided to represent these two cell types. The extracellular water, which includes all of the fluid outside of the cells, can be further subdivided into compartments which represent the interstitial fluid, circulating blood plasma, lymph, and transcellular water. The interstitial fluid surrounds cells outside of the vascular system whereas plasma is contained within the blood vessels. Avascular tissues such as dense connective tissue and cartilage contain interstitial water which slowly equilibrates with tracers used to determine extracellular fluid volume. For this reason, additional compartments are sometimes used to represent these avascular tissues. The average size of each compartment, in terms of percent body weight, has been determined for adult males and females. These compartments and the forces which cause flow between them are presented. The kidneys, a main compartment, receive about 25 percent of the cardiac output and filters out a fluid similar to plasma. The composition of this filtered fluid changes as it flows through the kidney tubules since compounds are continually being secreted and reabsorbed. Through this mechanism, the kidneys eliminate wastes while conserving body water, electrolytes, and metabolites. Since sodium accounts for over 90 percent of the cations in the extracellular fluid, and the number of cations is balanced by the number of anions, considering the renal handling sodium and water only should sufficiently describe the relationship between the plasma compartment and kidneys. A kidney function model is presented which has been adapted from a previous model of normal renal function in man. To test the validity of the proposed kidney model, results predicted by the model will be compared to actual data involving injected or ingested fluids and subsequent urine flow rates. Comparison of the model simulation to actual data following the ingestion of 1 liter of water is shown. The model simulation is also shown with actual data following the intravenous infusion of hypertonic saline.

A computational study of systemic hydration in vocal fold collision.

PubMed

Bhattacharya, Pinaki; Siegmund, Thomas

2014-01-01

Mechanical stresses develop within vocal fold (VF) soft tissues due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelity numerical computations are described, taking into account fully 3D geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak airflow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tend to increase the state of hydration of the VF tissue, whereas VF collision works to reduce hydration.

Virchow-Robin space and aquaporin-4: new insights on an old friend.

PubMed

Nakada, Tsutomu

2014-08-28

Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

Impairment of the glymphatic system after diabetes.

PubMed

Jiang, Quan; Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

2017-04-01

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application.

Impairment of the glymphatic system after diabetes

PubMed Central

Zhang, Li; Ding, Guangliang; Davoodi-Bojd, Esmaeil; Li, Qingjiang; Li, Lian; Sadry, Neema; Nedergaard, Maiken; Chopp, Michael; Zhang, Zhenggang

2016-01-01

The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphatic clearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes is known as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphatic clearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinal fluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2 diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficits detected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescent tracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitial fluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitatively evaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurological disorders, with potential clinical application. PMID:27306755

Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models.

PubMed

Sen, Arindam; Capitano, Maegan L; Spernyak, Joseph A; Schueckler, John T; Thomas, Seneca; Singh, Anurag K; Evans, Sharon S; Hylander, Bonnie L; Repasky, Elizabeth A

2011-06-01

Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment.

Effect of pre-donation fluid intake on fluid shift from interstitial to intravascular compartment in blood donors.

PubMed

Deepika, Chenna; Murugesan, Mohandoss; Shastry, Shamee

2018-02-01

Fluid shifts from interstitial to intravascular space during blood donation helps in compensating the lost blood volume. We aimed to determine the volume of fluid shift following donation in donors with and without pre-donation fluid intake. We studied the fluid shift in 325 blood donors prospectively. Donors were divided in groups- with no fluid intake (GI) and either water (GII) or oral rehydrating fluids (GIII) before donation. Fluid shift following donation was calculated based on the difference between the pre and post donation blood volume. The influence of oral fluid intake, age, gender and body mass index (BMI) on volume of fluid shift was analyzed. The fluid shift was significant between donors without fluids (GI: 127 ± 81 ml) and donors with fluid intake (GII & III: 96 ± 45 ml) (p < 0.05). The difference was not significant between donors with water intake (GII: 106 ± 52 ml) and oral rehydrating fluid intake (GIII: 87 ± 41 ml). The shifted fluid volume increased with increasing BMI and decreased with increasing age in females. The fluid shift increased in females than in males. The age, gender, BMI and VVR did not significantly contribute to the volume of fluid shift following donation. As per our observation, the oral fluids before donation might not contribute to increase in fluid shift in blood donors after donation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

PubMed

Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T

1997-03-01

A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

Fluid balance within the canine anterolateral compartment and its relationship to compartment syndromes.

PubMed

Hargens, A R; Akeson, W H; Mubarak, S J; Owen, C A; Evans, K L; Garetto, L P; Gonsalves, M R; Schmidt, D A

1978-06-01

Fluid homeostasis within muscle compartments is maintained by four pressures: capillary blood pressure, capillary blood oncotic pressure, tissue-fluid pressure, and tissue fluid oncotic pressure. As determined in the canine anterolateral compartment, capillary blood pressure is 25 +/- 3 millimeters of mercury; capillary blood oncotic pressure, 26 +/- 3 millimeters of mercury, tissue-pbessure, -2 +/- 2 millimeters of mercury; and tissue-fluid oncotic pressure, 11 +/- 1 millimeters of mercury. The wick technique allows direct measurement of tissue-fluid pressure in skeletal muscle and, with minor modifications, is adapted to collect microsamples of interstitial fluid for determinations of tissue-fluid oncotic pressure. The wick technique detects very slight fluctuations in intracompartmental pressure such as light finger compression, injection of small volumes of fluid, and even pulsation due to adjacent arterial pressure. Adjacent muscle compartments may contain different tissue-fluid pressure due to impermeable osseofascial barriers. Our results obtained in canine muscle compartments pressurized by infusion of autologous plasma suggest that risks of muscle damage are significant at intracompartmental pressures greater than thirty millimeters of mercury.

Orthostatic stress is necessary to maintain the dynamic range of cardiovascular control in space

NASA Technical Reports Server (NTRS)

Baisch, J. F.; Wolfram, G.; Beck, L.; Drummer, C.; Stormer, I.; Buckey, J.; Blomqvist, G.

2000-01-01

In the upright position, gravity fills the low-pressure systems of human circulation with blood and interstitial fluid in the sections below the diaphragm. Without gravity one pressure component in the vessels disappears and the relationship between hydrostatic pressure and oncotic pressure, which regulates fluid passage across the capillary endothelium in the terminal vascular bed, shifts constantly. The visible consequences of this are a puffy face and "bird" legs. The plasma volume shrinks in space and the range of cardiovascular control is reduced. When they stand up for the first time after landing, 30-50% of astronauts suffer from orthostatic intolerance. It remains unclear whether microgravity impairs cardiovascular reflexes, or whether it is the altered volume status that causes the cardiovascular instability following space flight. Lower body negative pressure was used in several space missions to stimulate the cardiovascular reflexes before, during and after a space flight. The results show that cardiovascular reflexes are maintained in microgravity. However, the astronauts' volume status changed in space, towards a volume-retracted state, as measurements of fluid-regulating hormones have shown. It can be hypothesized that the control of circulation and body fluid homeostasis in humans is adapted to their upright posture in the Earth's gravitational field. Autonomic control regulates fluid distribution to maintain the blood pressure in that posture, which most of us have to cope with for two-thirds of the day. A determined amount of interstitial volume is necessary to maintain the dynamic range of cardiovascular control in the upright posture; otherwise orthostatic intolerance may occur more often.

Evaluation of a Novel Glucose Area Under the Curve (AUC) Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring

PubMed Central

Maegawa, Hiroshi; Morino, Katsutaro; Nishio, Yoshihiko; Sato, Toshiyuki; Okada, Seiki; Kikkawa, Yasuo; Watanabe, Toshihiro; Nakajima, Hiromu; Kashiwagi, Atsunori

2016-01-01

Background Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. Methods Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. Results AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. Conclusion Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration. PMID:27535643

Evaluation of a Novel Glucose Area Under the Curve (AUC) Monitoring System: Comparison with the AUC by Continuous Glucose Monitoring.

PubMed

Ugi, Satoshi; Maegawa, Hiroshi; Morino, Katsutaro; Nishio, Yoshihiko; Sato, Toshiyuki; Okada, Seiki; Kikkawa, Yasuo; Watanabe, Toshihiro; Nakajima, Hiromu; Kashiwagi, Atsunori

2016-08-01

Management of postprandial hyperglycemia is a key aspect in diabetes treatment. We developed a novel system to measure glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET) for simple monitoring of postprandial glucose excursions. In this study, we evaluated the relationship between our system and continuous glucose monitoring (CGM) by comparing glucose AUC obtained using MIET with that obtained using CGM for a long duration. Twenty diabetic inpatients wearing a CGM system were enrolled. For MIET measurement, a plastic microneedle array was applied to the skin as pretreatment, and hydrogels were placed on the pretreated area to collect interstitial fluid. Hydrogels were replaced every 2 or 4 hours and AUC was predicted on the basis of glucose and sodium ion levels. AUC predicted by MIET correlated well with that measured by CGM (r=0.93). Good performances of both consecutive 2- and 4-hour measurements were observed (measurement error: 11.7%±10.2% for 2 hours and 11.1%±7.9% for 4 hours), indicating the possibility of repetitive measurements up to 8 hours. The influence of neither glucose fluctuation nor average glucose level over the measurement accuracy was observed through 8 hours. Our system showed good relationship with AUC values from CGM up to 8 hours, indicating that single pretreatment can cover a large portion of glucose excursion in a day. These results indicated possibility of our system to contribute to convenient monitoring of glucose excursions for a long duration.

In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle

PubMed Central

Gyenge, Christina C; Tenstad, Olav; Wiig, Helge

2003-01-01

In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5–7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues. PMID:12937287

In vivo determination of steric and electrostatic exclusion of albumin in rat skin and skeletal muscle.

PubMed

Gyenge, Christina C; Tenstad, Olav; Wiig, Helge

2003-11-01

In order to estimate the magnitude of electrostatic exclusion provided by the fixed negative charges of the skin and muscle interstitia of rat in vivo we measured the distribution volumes of two differently charged albumin probes within these tissues. An implanted osmotic pump was used to reach and maintain a steady-state extracellular concentration of a mixture containing two iodine-labelled probes: a charged-modified human serum albumin, cHSA (i.e. a positive probe, isoelectirc point (pI) = 7.6) and a native human serum albumin, HSA (i.e. a normally charged, negative probe, pI = 5.0). Steady-state tissue concentrations were achieved after intravenous infusion of probes for 5-7 days. At the end of this period the animals were nephrectomized and a bolus of 51Cr-EDTA was administered for estimating the extracellular volume. Plasma volumes were measured as 5-min distribution volume of 125I-HSA in separate experiments. The steady-state interstitial fluid concentrations of all probes were determined using nylon wicks implanted postmortem. Calculations of labelled probes were made for interstitial fluid volumes (Vi), extravascular albumin distribution volumes (Vav,a) and relative interstitial excluded volume fractions (Vex,a/Vi). We found that the positive probe is excluded from a significantly smaller fraction of the interstitium. Specifically, the average relative albumin exclusion fractions obtained were: 16% and 26% in skeletal muscle and 30% and 40% in skin, for cHSA and HSA, respectively. On average, the fixed negative charges of the interstitium are responsible for about 40% of the total albumin exclusion in skeletal muscle and 25% in the whole skin tissue and thus, contribute significantly to volume exclusion in these tissues.

Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.

PubMed

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells.

Protein vs electrolytes and all of the Starling forces.

PubMed

Peters, R M; Hargens, A R

1981-10-01

Hemodilution-induced reductions of the intravascular protein concentration in patients and experimental animals with intact capillaries do not lead to pulmonary edema, despite significant increases in the amount of extravascular water in the systemic interstitial space. The protective factors are a drop in the extravascular concentration of protein, a rise in interstitial tissue pressure, and an increase in lymph flow. If the capillary endothelium is damaged, protein leaks into the extravascular space, and protein infusion has a diminished effect on fluid exchange across the capillary. Whether capillaries are intact or injured, prevention of increases in capillary hydrostatic pressure is the most important factor in preventing pulmonary edema. Administration of hypertonic fluids may provide a useful method of limiting total fluid infusion and reducing cell swelling after blood loss.

Fluid shifts and muscle function in humans during acute simulated weightlessness

NASA Technical Reports Server (NTRS)

Hargens, A. R.; Tipton, C. M.; Gollnick, P. D.; Mubarak, S. J.; Tucker, B. J.; Akeson, W. H.

1983-01-01

The acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surface reflex time were studied in eight supine human subjects who were placed in a 5 degrees head-down tilt position for 8 hr. Results show a cephalic fluid shift from the legs as indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. The interstitial fluid pressure in the tibialis anterior muscle and subcutaneous tissue of the lower leg was found to fall significantly, while other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. The total water content of the soleus muscle was unchanged during the head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged, while the triceps surae reflex time associated with plantar flexion movement slowed slightly. These results demonstrate a dehydration effect of head-down tilt on muscle and subcutaneous tissue of the lower leg that may affect muscle function.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

PubMed

Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

2014-08-21

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and may thus lead to sub-optimal outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

2014-01-01

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response slows down as the tumor shrinks due to the heterogeneity and low concentration of agents in the tumor interior compared with the cases where other pathological effects may combine to flatten the IFP and thus reduce the heterogeneity. We conclude that dual normalizations of the micronevironment - both the vasculature and the interstitium - are needed to maximize the effects of chemotherapy, while normalization of only one of these may be insufficient to overcome the physical resistance and thus leads to sub-optimal outcomes. PMID:24751927

A mathematical model of intestinal oedema formation.

PubMed

Young, Jennifer; Rivière, Béatrice; Cox, Charles S; Uray, Karen

2014-03-01

Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall.

Modelling Transcapillary Transport of Fluid and Proteins in Hemodialysis Patients

PubMed Central

Pietribiasi, Mauro; Waniewski, Jacek; Załuska, Alicja; Załuska, Wojciech; Lindholm, Bengt

2016-01-01

Background The kinetics of protein transport to and from the vascular compartment play a major role in the determination of fluid balance and plasma refilling during hemodialysis (HD) sessions. In this study we propose a whole-body mathematical model describing water and protein shifts across the capillary membrane during HD and compare its output to clinical data while evaluating the impact of choosing specific values for selected parameters. Methods The model follows a two-compartment structure (vascular and interstitial space) and is based on balance equations of protein mass and water volume in each compartment. The capillary membrane was described according to the three-pore theory. Two transport parameters, the fractional contribution of large pores (αLP) and the total hydraulic conductivity (LpS) of the capillary membrane, were estimated from patient data. Changes in the intensity and direction of individual fluid and solute flows through each part of the transport system were analyzed in relation to the choice of different values of small pores radius and fractional conductivity, lymphatic sensitivity to hydraulic pressure, and steady-state interstitial-to-plasma protein concentration ratio. Results The estimated values of LpS and αLP were respectively 10.0 ± 8.4 mL/min/mmHg (mean ± standard deviation) and 0.062 ± 0.041. The model was able to predict with good accuracy the profiles of plasma volume and serum total protein concentration in most of the patients (average root-mean-square deviation < 2% of the measured value). Conclusions The applied model provides a mechanistic interpretation of fluid transport processes induced by ultrafiltration during HD, using a minimum of tuned parameters and assumptions. The simulated values of individual flows through each kind of pore and lymphatic absorption rate yielded by the model may suggest answers to unsolved questions on the relative impact of these not-measurable quantities on total vascular refilling and fluid balance. PMID:27483369

Association of gas hydrate formation in fluid discharges with anomalous hydrochemical profiles

NASA Astrophysics Data System (ADS)

Matveeva, T.

2009-04-01

Numerous investigations worldwide have shown that active underwater fluid discharge produces specific structures on the seafloor such as submarine seepages, vents, pockmarks, and collapse depressions. Intensive fluxes of fluids, especially of those containing hydrocarbon gases, result in specific geochemical and physical conditions favorable for gas hydrate (GH) formation. GH accumulations associated with fluid discharge are usually controlled by fluid conduits such as mud volcanoes, diapirs or faults. During last decade, subaqueous GHs become the subject of the fuel in the nearest future. However, the expediency of their commercial development can be proved solely by revealing conditions and mechanisms of GH formation. Kinetic of GH growth (although it is incompletely understood) is one of the important parameters controlling their formation among with gas solubility, pressure, temperature, gas quantity and others. Original large dataset on hydrate-related interstitial fluids obtained from different fluid discharge areas at the Sea of Okhotsk, Black Sea, Gulf of Cadiz, Lake Baikal (Eastern Siberia) allow to suggest close relation of the subaqueous GH formation process to anomalous hydrochemical profiles. We have studied the chemical and isotopic composition of interstitial fluids from GH-bearing and GH-free sediments obtained at different GH accumulations. Most attention was paid to possible influence of the interstitial fluid chemistry on the kinetic of GH formation in a porous media. The influence of salts on methane solubility within hydrate stability zones was considered by Handa (1990), Zatsepina & Buffet (1998), and later by Davie et al. (2004) from a theoretical point of view. Our idea is based on the experimentally proved fact that fugacity coefficient of methane dissolved in saline gas-saturated water which is in equilibrium with hydrates, is higher than that in more fresh water though the solubility is lower. Therefore, if a gradient of water salinity exist under conditions of hydrate stability, diffusion of methane induces hydrate formation by segregation on the outside a boundary fresher/saline water. Geochemical analysis of the interstitial fluids was used to define the mechanisms of GH accumulation and spatial distribution pattern of GHs in sediments from gas seeps abundant off NE Sakhaline Island (Sea of Okhotsk) (Matveeva et al., 2005; Mazurenko et al., submitted). A model of the ascending fluid discharge along one of the seeps named CHAOS was made based on the measured chlorinity (salinity function) of the pore waters and calculated chlorinity gradients. The chloride ion distributionprofiles with depth at the CHAOS site represent alike increasing and decreasing trends both in hydrate-bearing and hydrate-free cores. The model testifies an upward water infiltration of more saline water in vicinity of coring stations recovered GHs and relatively desalinated water mostly around those hydrate-free. It was established that GH formation at the CHAOS site is focused at the locations of intensive ascending flow of water enriched by salts that is probably function of gas solubility in water in the equilibrium with hydrate supposing that the feature is responsible for the hydrate formation just at the locations of the saline water up flows (other conditions being equal). Another case study supporting direct relation of GH formation with anomalous fluids and possible GH formation just on the interface of water flows with different salinity (defining chemical potentials of the water) is fresh-water GH accumulation at the Malenkiy fluid vent in the southern basin of Lake Baikal (Matveeva et al., 2003). The GH accumulation characterizes by heterogeneity in the spatial distribution of GH within a very small vent area. The spatial distribution of the GH-bearing and gas-saturated sediments suggests that several small fluid vents exist within the Malenkiy structure. Based on coring results, the size of these vents should not exceed a few meters. Interstitial water chemistry data indicates that water discharged within the Malenkiy vent is enriched with salts, especially Ca, Cl, and SO4 ions. The ascending water delivering gas into the GH stability zone is thought to be the main GH-forming fluid. Geochemical data suggest that the GH in the subsurface sediments of Lake Baikal originated from a deep source of water with anomalous composition assumed to be derived from buried paleolakes. As a whole, the GH accumulation corresponds to the area of the Malenkiy structure and is represented by several small scale GH occurrences coincident with local fluid discharge manifestations. The data obtained may serve as useful tool for development of geological and hydrogeochemical models of separate GH accumulations forming in the fluid discharge areas. The models on may also serve as a base for the gas inventory of the GH accumulations.

In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis

PubMed Central

2013-01-01

Background The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. The link between apolipoprotein E (apoE) and Alzheimer’s disease is likely due in large part to the impact of apoE on the metabolism of amyloid β (Aβ) within the brain. Manipulation of apoE levels and lipidation within the brain has been proposed as a therapeutic target for the treatment of Alzheimer’s disease. However, we know little about the dynamic regulation of apoE levels and lipidation within the central nervous system. We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes. Results We were able to recover apoE using microdialysis from human cerebrospinal fluid (CSF) in vitro and mouse brain parenchyma in vivo. Microdialysis probes were inserted into the hippocampus of wild-type mice and interstitial fluid was collected for 36 hours. Levels of apoE within the microdialysis samples were determined by ELISA. The levels of apoE were found to be relatively stable over 36 hours. No apoE was detected in microdialysis samples from apoE KO mice. Administration of the RXR agonist bexarotene increased ISF apoE levels while ISF Aβ levels were decreased. Extrapolation to zero-flow analysis allowed us to determine the absolute recoverable concentration of apoE3 in the brain ISF of apoE3 KI mice. Furthermore, analysis of microdialysis samples by non-denaturing gel electrophoresis determined lipidated apoE particles in microdialysis samples were consistent in size with apoE particles from CSF. Finally, we found that the concentration of apoE in the brain ISF was dependent upon apoE isoform in human apoE KI mice, following the pattern apoE2>apoE3>apoE4. Conclusions We are able to collect lipidated apoE from the brain of awake and freely moving mice and monitor apoE levels over the course of several hours from a single mouse. Our technique enables assessment of brain apoE dynamics under physiological and pathophysiological conditions and in response to therapeutic interventions designed to affect apoE levels and lipidation within the brain. PMID:23601557

Computer Simulations of the Tumor Vasculature: Applications to Interstitial Fluid Flow, Drug Delivery, and Oxygen Supply.

PubMed

Welter, Michael; Rieger, Heiko

2016-01-01

Tumor vasculature, the blood vessel network supplying a growing tumor with nutrients such as oxygen or glucose, is in many respects different from the hierarchically organized arterio-venous blood vessel network in normal tissues. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature. Integrative models, based on detailed experimental data and physical laws, implement, in silico, the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. This chapter provides an overview over the current status of computer simulations of vascular remodeling during tumor growth including interstitial fluid flow, drug delivery, and oxygen supply within the tumor. The model predictions are compared with experimental and clinical data and a number of longstanding physiological paradigms about tumor vasculature and intratumoral solute transport are critically scrutinized.

Smart medical systems with application to nutrition and fitness in space

NASA Technical Reports Server (NTRS)

Soller, Babs R.; Cabrera, Marco; Smith, Scott M.; Sutton, Jeffrey P.

2002-01-01

Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiologic status in real time. In a smart medical system, sensor arrays assess subject status, which is interpreted by computer processors that analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, thus closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend inflight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near-infrared spectroscopy can be used to non-invasively measure several blood and tissue parameters that are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The non-invasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors is also described.

Smart Medical Systems with Application to Nutrition and Fitness in Space

NASA Technical Reports Server (NTRS)

Soller, Babs R.; Cabrera, Marco; Smith, Scott M.; Sutton, Jeffrey P.

2002-01-01

Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiological status in real time. In a smart medical system sensor arrays assess subject status, which are interpreted by computer processors which analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend in-flight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near infrared spectroscopy can be used to noninvasively measure several blood and tissue parameters which are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The noninvasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors are also described.

Release of enzymes from cells: transport and distribution within the extracellular space.

PubMed

Mattenheimer, H; Friedel, R

1977-01-01

The distribution in the extracellular space of enzymes released from organ cells was investigated using three models: (1) comparison of enzyme activities in blood plasma and lymph of the ductus thoracicus (dog) and plasma and intestinal lymph (rat); (2) i.v. injection of heterologous, homologous and autologous enzymes in order to increase acutely the activities and to measure the rate constants for the distribution and elimination of the enzymes (rat); or (3) plasmapheresis in order to create an enzyme activity gradient from the interstitial space and to determine the rate constants for the reestablishment of the equilibrium between the extra and intravascular compartments (rat). The results suggest that the enzymes are mainly released into the interstitial fluid and transported via the lymph into the intravascular compartment. From there the enzymes diffuse back into the interstitial compartment and are eliminated by a yet unknown mechanism. Transport of enzymes across the capillary membranes in both directions depends on (1) the permeability of the capillary membranes, which varies from region to region and (2) the molecular seizes of the enzymes.

Estimation of blood flow heterogeneity in human skeletal muscle using intravascular tracer data: importance for modeling transcapillary exchange.

PubMed

Vicini, P; Bonadonna, R C; Lehtovirta, M; Groop, L C; Cobelli, C

1998-01-01

Distributed models of blood-tissue exchange are widely used to measure kinetic events of various solutes from multiple tracer dilution experiments. Their use requires, however, a careful description of blood flow heterogeneity along the capillary bed. Since they have mostly been applied in animal studies, direct measurement of the heterogeneity distribution was possible, e.g., with the invasive microsphere method. Here we apply distributed modeling to a dual tracer experiment in humans, performed using an intravascular (indocyanine green dye, subject to distribution along the vascular tree and confined to the capillary bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary transfer across the capillary membrane in the interstitial fluid) tracer. The goal is to measure relevant parameters of transcapillary exchange in human skeletal muscle. We show that assuming an accurate description of blood flow heterogeneity is crucial for modeling, and in particular that assuming for skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is inappropriate. The same reason prevents the use of the common method of estimating the input function of the distributed model via deconvolution, which assumes a known blood flow heterogeneity, either defined from literature or measured, when possible. We present a novel approach for the estimation of blood flow heterogeneity in each individual from the intravascular tracer data. When this newly estimated blood flow heterogeneity is used, a more satisfactory model fit is obtained and it is possible to reliably measure parameters of capillary membrane permeability-surface product and interstitial fluid volume describing transcapillary transfer in vivo.

A Computational Study of Systemic Hydration in Vocal Fold Collision

PubMed Central

Bhattacharya, Pinaki; Siegmund, Thomas

2013-01-01

Mechanical stresses develop within vocal fold (VF) soft tissues, due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelty numerical computations are described taking into account fully three-dimensional geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak air-flow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tends to increase the state of hydration of the VF tissue whereas VF collision works to reduce hydration. PMID:23531170

Asbestos bodies in bronchoalveolar lavage fluid. A study of 20 asbestos-exposed individuals and comparison to patients with other chronic interstitial lung diseases

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

Roggli, V.L.; Piantadosi, C.A.; Bell, D.Y.

1986-09-01

We studied the asbestos body (AB) content of bronchoalveolar lavage fluid from 20 patients with a history of occupational asbestos exposure, 31 patients with sarcoidosis and 5 patients with idiopathic pulmonary fibrosis. The cellular lavage pellet was digested in sodium hypochlorite and filtered onto Nuclepore filters for AB quantification by light microscopy. ABs were found in 15 of 20 asbestos-exposed individuals, 9 of 31 sarcoidosis cases and 2 of 5 patients with idiopathic pulmonary fibrosis. There was a statistically significant difference in the number of ABs per million cells recovered or per milliliter of recovered lavage fluid in the asbestos-exposedmore » group as compared to the other categories of chronic interstitial lung disease. The highest levels occurred in patients with asbestosis. Large numbers of asbestos bodies in the lavage fluid (greater than 1 AB/10(6) cells) were indicative of considerable occupational asbestos exposure, whereas occasional bodies were a nonspecific finding.« less

Fluid Mechanics of the Vascular Basement Membrane in the Brain

NASA Astrophysics Data System (ADS)

Coloma, Mikhail; Hui, Jonathan; Chiarot, Paul; Huang, Peter; Carare, Roxana; McLeod, Kenneth; Schaffer, David

2013-11-01

Beta-amyloid is a normal product of brain metabolic function and is found within the interstitial fluid of the brain. Failure of the clearance of beta-amyloid from the aging brain leads to its accumulation within the walls of arteries and to Alzheimer's disease. The vascular basement membrane (VBM) within the walls of cerebral arteries surrounds the spirally arranged smooth muscle cells and represents an essential pathway for removal of beta-amyloid from the brain. This process fails with the stiffening of arterial walls associated with aging. In this study we hypothesize that the deformation of the VBM associated with arterial pulsations drives the interstitial fluid to drain in the direction opposite of the arterial blood flow. This hypothesis is theoretically investigated by modeling the VBM as a thin, coaxial, fluid-filled porous medium surrounding a periodically deforming cylindrical tube. Flow and boundary conditions required to achieve such a backward clearance are derived through a control volume analysis of mass, momentum, and energy.

Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

PubMed Central

Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

2015-01-01

Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid β42 concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment. PMID:25938590

Fluid Shifts

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Hargens, A.; Dulchavsky, S.; Ebert, D.; Lee, S.; Laurie, S.; Garcia, K.; Sargsyan, A.; Martin, D.; Lui, J.;

Influence of vascular normalization on interstitial flow and delivery of liposomes in tumors

NASA Astrophysics Data System (ADS)

Ozturk, Deniz; Yonucu, Sirin; Yilmaz, Defne; Burcin Unlu, Mehmet

2015-02-01

Elevated interstitial fluid pressure is one of the barriers of drug delivery in solid tumors. Recent studies have shown that normalization of tumor vasculature by anti-angiogenic factors may improve the delivery of conventional cytotoxic drugs, possibly by increasing blood flow, decreasing interstitial fluid pressure, and enhancing the convective transvascular transport of drug molecules. Delivery of large therapeutic agents such as nanoparticles and liposomes might also benefit from normalization therapy since their transport depends primarily on convection. In this study, a mathematical model is presented to provide supporting evidence that normalization therapy may improve the delivery of 100 nm liposomes into solid tumors, by both increasing the total drug extravasation and providing a more homogeneous drug distribution within the tumor. However these beneficial effects largely depend on tumor size and are stronger for tumors within a certain size range. It is shown that this size effect may persist under different microenvironmental conditions and for tumors with irregular margins or heterogeneous blood supply.

PARTICLE IMAGE VELOCIMETRY MEASUREMENTS IN A REPRESENTATIVE GAS-COOLED PRISMATIC REACTOR CORE MODEL: FLOW IN THE COOLANT CHANNELS AND INTERSTITIAL BYPASS GAPS

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

Thomas E. Conder; Richard Skifton; Ralph Budwig

Core bypass flow is one of the key issues with the prismatic Gas Turbine-Modular Helium Reactor, and it refers to the coolant that navigates through the interstitial, non-cooling passages between the graphite fuel blocks instead of traveling through the designated coolant channels. To determine the bypass flow, a double scale representative model was manufactured and installed in the Matched Index-of-Refraction flow facility; after which, stereo Particle Image Velocimetry (PIV) was employed to measure the flow field within. PIV images were analyzed to produce vector maps, and flow rates were calculated by numerically integrating over the velocity field. It was foundmore » that the bypass flow varied between 6.9-15.8% for channel Reynolds numbers of 1,746 and 4,618. The results were compared to computational fluid dynamic (CFD) pre-test simulations. When compared to these pretest calculations, the CFD analysis appeared to under predict the flow through the gap.« less

Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: A multiscale approach.

PubMed

Miri, Amir K; Heris, Hossein K; Mongeau, Luc; Javid, Farhad

2014-02-01

It is hypothesized that the bulk viscoelasticity of soft tissues is determined by two length-scale-dependent mechanisms: the time-dependent response of the extracellular matrix (ECM) proteins at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter is governed by poroelasticity theory assuming free motion of the interstitial fluid within the porous ECM structure. In a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. J. Mech. Behav. Biomed. Mater.), atomic force microscopy was used to measure the response of porcine vocal folds to a creep loading and a 50-nm sinusoidal oscillation. A constitutive model was calibrated and verified using a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A generally good correlation was obtained between the predicted variation of the viscoelastic moduli with depth and that of hyaluronic acids in vocal fold tissue. We conclude that hyaluronic acids may regulate vocal fold viscoelasticity. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. © 2013 Elsevier Ltd. All rights reserved.

Quantification of Lacunar-Canalicular Interstitial Fluid Flow Through Computational Modeling of Fluorescence Recovery After Photobleaching.

PubMed

Kwon, Ronald Y; Frangos, John A

2010-09-01

Skeletal adaptation to mechanical loading has been widely hypothesized to involve the stimulation of osteocytes by interstitial fluid flow (IFF). However, direct investigation of this hypothesis has been difficult due in large part to the inability to directly measure IFF velocities within the lacunar-canalicular system. Measurements of fluorescence recovery after photobleaching (FRAP) within individual lacunae could be used to quantify lacunar-canalicular IFF when combined with mathematical modeling. In this study, we used a computational transport model to characterize the relationship between flow frequency (0.5-10 Hz), peak flow velocity (0-300 μm/s), tracer diffusion coefficient (100-300 μm(2)/s), and transport enhancement (i.e., (k/k(0)) - 1, where k and k(0) are the transport rates in the presence/absence of flow) during lacunar FRAP investigations. We show that this relationship is well described by a simple power law with frequency-dependent coefficients, and is relatively insensitive to variations in lacunar geometry. Using this power law relationship, we estimated peak IFF velocities in hindlimb mice subjected to intramedullary pressurization using values of k and k(0) previously obtained from ex vivo lacunar FRAP investigations. Together, our findings suggest that skeletal adaptation in hindlimb suspended mice subjected to dynamic intramedullary pressure occurred in the presence of IFF at levels associated with physiological loading.

Quantification of Lacunar–Canalicular Interstitial Fluid Flow Through Computational Modeling of Fluorescence Recovery After Photobleaching

PubMed Central

Kwon, Ronald Y.; Frangos, John A.

2010-01-01

Skeletal adaptation to mechanical loading has been widely hypothesized to involve the stimulation of osteocytes by interstitial fluid flow (IFF). However, direct investigation of this hypothesis has been difficult due in large part to the inability to directly measure IFF velocities within the lacunar–canalicular system. Measurements of fluorescence recovery after photobleaching (FRAP) within individual lacunae could be used to quantify lacunar–canalicular IFF when combined with mathematical modeling. In this study, we used a computational transport model to characterize the relationship between flow frequency (0.5–10 Hz), peak flow velocity (0–300 μm/s), tracer diffusion coefficient (100–300 μm2/s), and transport enhancement (i.e., (k/k0) − 1, where k and k0 are the transport rates in the presence/absence of flow) during lacunar FRAP investigations. We show that this relationship is well described by a simple power law with frequency-dependent coefficients, and is relatively insensitive to variations in lacunar geometry. Using this power law relationship, we estimated peak IFF velocities in hindlimb mice subjected to intramedullary pressurization using values of k and k0 previously obtained from ex vivo lacunar FRAP investigations. Together, our findings suggest that skeletal adaptation in hindlimb suspended mice subjected to dynamic intramedullary pressure occurred in the presence of IFF at levels associated with physiological loading. PMID:21076644

Leg blood flow is impaired during small muscle mass exercise in patients with COPD.

PubMed

Iepsen, U W; Munch, G W; Rugbjerg, M; Ryrsø, C K; Secher, N H; Hellsten, Y; Lange, P; Pedersen, B K; Thaning, P; Mortensen, S P

2017-09-01

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O 2 /min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD ( P < 0.05) and also tended to be higher during exercise ( P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1. NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD. Copyright © 2017 the American Physiological Society.

Fluid Mechanics, Arterial Disease, and Gene Expression.

PubMed

Tarbell, John M; Shi, Zhong-Dong; Dunn, Jessilyn; Jo, Hanjoong

2014-01-01

This review places modern research developments in vascular mechanobiology in the context of hemodynamic phenomena in the cardiovascular system and the discrete localization of vascular disease. The modern origins of this field are traced, beginning in the 1960s when associations between flow characteristics, particularly blood flow-induced wall shear stress, and the localization of atherosclerotic plaques were uncovered, and continuing to fluid shear stress effects on the vascular lining endothelial) cells (ECs), including their effects on EC morphology, biochemical production, and gene expression. The earliest single-gene studies and genome-wide analyses are considered. The final section moves from the ECs lining the vessel wall to the smooth muscle cells and fibroblasts within the wall that are fluid me chanically activated by interstitial flow that imposes shear stresses on their surfaces comparable with those of flowing blood on EC surfaces. Interstitial flow stimulates biochemical production and gene expression, much like blood flow on ECs.

VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer

PubMed Central

Gerstner, Elizabeth R.; Duda, Dan G.; di Tomaso, Emmanuelle; Ryg, Peter A.; Loeffler, Jay S.; Sorensen, A. Gregory; Ivy, Percy; Jain, Rakesh K.; Batchelor, Tracy T.

2016-01-01

Most brain tumors oversecrete vascular endothelial growth factor (VEGF), which leads to an abnormally permeable tumor vasculature. This hyperpermeability allows fluid to leak from the intravascular space into the brain parenchyma, which causes vasogenic cerebral edema and increased interstitial fluid pressure. Increased interstitial fluid pressure has an important role in treatment resistance by contributing to tumor hypoxia and preventing adequate tumor penetration of chemotherapy agents. In addition, edema and the corticosteroids needed to control cerebral edema cause significant morbidity and mortality. Agents that block the VEGF pathway are able to decrease vascular permeability and, thus, cerebral edema, by restoring the abnormal tumor vasculature to a more normal state. Decreasing cerebral edema minimizes the adverse effects of corticosteroids and could improve clinical outcomes. Anti-VEGF agents might also be useful in other cancer-related conditions that increase vascular permeability, such as malignant pleural effusions or ascites. PMID:19333229

Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

PubMed

Nagahashi, Masayuki; Yamada, Akimitsu; Miyazaki, Hiroshi; Allegood, Jeremy C; Tsuchida, Junko; Aoyagi, Tomoyoshi; Huang, Wei-Ching; Terracina, Krista P; Adams, Barbara J; Rashid, Omar M; Milstien, Sheldon; Wakai, Toshifumi; Spiegel, Sarah; Takabe, Kazuaki

2016-06-01

The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

Measurement of glucose area under the curve using minimally invasive interstitial fluid extraction technology: evaluation of glucose monitoring concepts without blood sampling.

PubMed

Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Watanabe, Toshihiro; Maekawa, Yasunori; Isobe, Kazuki; Koike, Reona; Nakajima, Hiromu; Asano, Kaoru

2011-12-01

Monitoring postprandial hyperglycemia is crucial in treating diabetes, although its dynamics make accurate monitoring difficult. We developed a new technology for monitoring postprandial hyperglycemia using interstitial fluid (ISF) extraction technology without blood sampling. The glucose area under the curve (AUC) using this system was measured as accumulated ISF glucose (IG) with simultaneous calibration with sodium ions. The objective of this study was to evaluate this technological concept in healthy individuals. Minimally invasive ISF extraction technology (MIET) comprises two steps: pretreatment with microneedles and ISF accumulation over a specific time by contact with a solvent. The correlation between glucose and sodium ion levels using MIET was evaluated in 12 subjects with stable blood glucose (BG) levels during fasting. BG and IG time courses were evaluated in three subjects to confirm their relationship while BG was fluctuating. Furthermore, the accuracy of glucose AUC measurements by MIET was evaluated several hours after a meal in 30 subjects. A high correlation was observed between glucose and sodium ion levels when BG levels were stable (R=0.87), indicating that sodium ion is a good internal standard for calibration. The variation in IG and BG with MIET was similar, indicating that IG is an adequate substitute for BG. Finally, we showed a strong correlation (R=0.92) between IG-AUC and BG-AUC after a meal. These findings validate the adequacy of glucose AUC measurements using MIET. Monitoring glucose using MIET without blood sampling may be beneficial to patients with diabetes.

Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

PubMed

Tien, Joe; Truslow, James G; Nelson, Celeste M

2012-01-01

This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

Characterization of Breast Cancer Interstitial Fluids by TmT Labeling, LTQ-Orbitrap Velos Mass Spectrometry and Pathway Analysis

PubMed Central

Cinzia, Raso; Carlo, Cosentino; Marco, Gaspari; Natalia, Malara; Xuemei, Han; Daniel, McClatchy; Kyu, Park Sung; Maria, Renne; Nuria, Vadalà; Ubaldo, Prati; Giovanni, Cuda; Vincenzo, Mollace; Francesco, Amato; Yates, John R.

2012-01-01

Cancer is currently considered as the end point of numerous genomic and epigenomic mutations and as the result of the interaction of transformed cells within the stromal microenvironment. The present work focuses on breast cancer, one of the most common malignancies affecting the female population in industrialized countries. In this study we perform a proteomic analysis of bioptic samples from human breast cancer, namely interstitial fluids and primary cells, normal vs disease tissues, using Tandem mass Tags (TmT) quantitative mass spectrometry combined with the MudPIT technique. To the best of our knowledge this work, with over 1700 proteins identified, represents the most comprehensive characterization of the breast cancer interstitial fluid proteome to date. Network analysis was used to identify functionally active networks in the breast cancer associated samples. From the list of differentially expressed genes we have retrieved the associated functional interaction networks. Many different signaling pathways were found activated, strongly linked to invasion, metastasis development, proliferation and with a significant cross-talking rate. This pilot study presents evidence that the proposed quantitative proteomic approach can be applied to discriminate between normal and tumoral samples and for the discovery of yet unknown carcinogenesis mechanisms and therapeutic strategies. PMID:22563702

Overview of Methods for Overcoming Hindrance to Drug Delivery to Tumors, with Special Attention to Tumor Interstitial Fluid

PubMed Central

Baronzio, Gianfranco; Parmar, Gurdev; Baronzio, Miriam

2015-01-01

Every drug used to treat cancer (chemotherapeutics, immunological, monoclonal antibodies, nanoparticles, radionuclides) must reach the targeted cells through the tumor environment at adequate concentrations, in order to exert their cell-killing effects. For any of these agents to reach the goal cells, they must overcome a number of impediments created by the tumor microenvironment (TME), beginning with tumor interstitial fluid pressure (TIFP), and a multifactorial increase in composition of the extracellular matrix (ECM). A primary modifier of TME is hypoxia, which increases the production of growth factors, such as vascular endothelial growth factor and platelet-derived growth factor. These growth factors released by both tumor cells and bone marrow recruited myeloid cells form abnormal vasculature characterized by vessels that are tortuous and more permeable. Increased leakiness combined with increased inflammatory byproducts accumulates fluid within the tumor mass (tumor interstitial fluid), ultimately creating an increased pressure (TIFP). Fibroblasts are also up-regulated by the TME, and deposit fibers that further augment the density of the ECM, thus, further worsening the TIFP. Increased TIFP with the ECM are the major obstacles to adequate drug delivery. By decreasing TIFP and ECM density, we can expect an associated rise in drug concentration within the tumor itself. In this overview, we will describe all the methods (drugs, nutraceuticals, and physical methods of treatment) able to lower TIFP and to modify ECM used for increasing drug concentration within the tumor tissue. PMID:26258072

Patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma.

PubMed

Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu

2012-05-01

To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.

Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model

PubMed Central

Welter, Michael; Rieger, Heiko

2013-01-01

Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells. PMID:23940570

Fluid and Electrolyte Balance model (FEB)

NASA Technical Reports Server (NTRS)

Fitzjerrell, D. G.

1973-01-01

The effects of various oral input water loads on solute and water distribution throughout the body are presented in the form of a model. The model was a three compartment model; the three compartments being plasma, interstitial fluid and cellular fluid. Sodium, potassium, chloride and urea were the only major solutes considered explicitly. The control of body water and electrolyte distribution was affected via drinking and hormone levels.

Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

DTIC Science & Technology

1979-06-19

The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

Abnormal myocardial fluid retention as an early manifestation of ischemic injury.

PubMed Central

Willerson, J. T.; Scales, F.; Mukherjee, A.; Platt, M.; Templeton, G. H.; Fink, G. S.; Buja, L. M.

1977-01-01

Fifty-seven isolated, blood perfused, continuously weighed canine hearts have been utilized to study the development of abnormal myocardial fluid retention during early myocardial ischemic injury. Inflatable balloon catheters were positioned around the left anterior descending coronary arteries (LAD) of 54 hearts or the proximal left circumflex coronary arteries of three hearts for study of the following intervals of coronary occlusion: a) 10 minutes followed by 20 minutes of reflow, b) 40 minutes followed by either no reflow or by 20 minutes of reflow, and c) 60 minutes without reflow. After 60 minutes of fixed coronary occlusion, histologic and ultrastructural examination revealed mild swelling of many ischemic cardiac muscle cells in the absence of interstitial edema, cardiac weight gain, and obvious structural defects in cell membrane integrity. After 40 minutes of coronary occlusion and 20 minutes of reflow, significant cardiac weight gain occurred in association with characteristic alterations in the ischemic region, including widespread interstitial edema and focal vascular congestion and hemorrhage and swelling of cardiac muscle cells. Focal structural defects in cell membrane integrity were also noted. The development of abnormal myocardial fluid retention after 40 minutes of LAD occlusion occurred in association with a significant reduction in sodium-potassium-ATPase activity in the ischemic area, but with no significant alteration in either creatine phosphokinase or citrate synthase activity in the same region. Despite the abnormal myocardial fluid retention in these hearts, it was possible pharmacologically to vasodilate coronary vessels with adenosine and nitroglycerin infusion to maintain a consistently high coronary flow following release of the coronary occlusion after 40 minutes and to even exceed initial hyperemic flow values following release of the occlusion when adenosine and nitroglycerin infusion was delayed until 15 minutes after reflow. Thus, the data indicate that impaired cell volume regulation and interstitial fluid accumulation and focal structural defects in cell membrane integrity are early manifestations of ischemic injury followed by reflow, but fail to establish a major role for the abnormal fluid retention in altering coronary blood flow prior to the development of extensive myocardial necrosis. In contrast, fixed coronary occlusion for 60 minutes results in mild intracellular swelling but no significant interstitial edema and no obvious structural defects in cell membrane integrity. Images Figure 1 Figure 5 Figure 6 Figure 2 Figure 3 Figure 4 PMID:139829

Hormonal regulation of fluid and electrolyte metabolism during periods of headward fluid shifts

NASA Technical Reports Server (NTRS)

Keil, Lanny C.; Severs, W. B.; Thrasher, T.; Ramsay, D. J.

1991-01-01

In the broadest sense, this project evaluates how spaceflight induced shifts of blood and interstitial fluids into the thorax affect regulation by the central nervous system (CNS) of fluid-electrolyte hormone secretion. Specifically, it focuses on the role of hormones related to salt/water balance and their potential function in the control of intracranial pressure and cerebrospinal fluid (CSF) composition. Fluid-electrolyte status during spaceflight gradually equilibrates, with a reduction in all body fluid compartments. Related to this is the cardiovascular deconditioning of spaceflight which is manifested upon return to earth as orthostatic intolerance.

Transport of fluid and solutes in the body I. Formulation of a mathematical model.

PubMed

Gyenge, C C; Bowen, B D; Reed, R K; Bert, J L

1999-09-01

A compartmental model of short-term whole body fluid, protein, and ion distribution and transport is formulated. The model comprises four compartments: a vascular and an interstitial compartment, each with an embedded cellular compartment. The present paper discusses the assumptions on which the model is based and describes the equations that make up the model. Fluid and protein transport parameters from a previously validated model as well as ionic exchange parameters from the literature or from statistical estimation [see companion paper: C. C. Gyenge, B. D. Bowen, R. K. Reed, and J. L. Bert. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1228-H1240, 1999] are used in formulating the model. The dynamic model has the ability to simulate 1) transport across the capillary membrane of fluid, proteins, and small ions and their distribution between the vascular and interstitial compartments; 2) the changes in extracellular osmolarity; 3) the distribution and transport of water and ions associated with each of the cellular compartments; 4) the cellular transmembrane potential; and 5) the changes of volume in the four fluid compartments. The validation and testing of the proposed model against available experimental data are presented in the companion paper.

Action of polysaccharides of similar average mass but differing molecular volume and charge on fluid drainage through synovial interstitium in rabbit knees

PubMed Central

Scott, D; Coleman, P J; Mason, R M; Levick, J R

2000-01-01

Hyaluronan (HA), an anionic polysaccharide of synovial fluid, attenuates fluid loss from joints as joint pressure is raised (‘outflow buffering’). The buffering is thought to depend on the expanded molecular domain of the polymer, which causes reflection by synovial extracellular matrix, leading to flow-dependent concentration polarization. We therefore assessed the effects of polysaccharides of differing average molecular volume and charge. Trans-synovial fluid drainage(Q̇s) was measured at controlled joint fluid pressure (Pj) in knees of anaesthetized rabbits. The joints were infused with polydisperse HA of weight-average mass 2100 kDa (4 mg ml−1, n = 17), with polydisperse neutral dextran of similar average mass (2000 kDa; n = 7) or with Ringer solution vehicle (n = 2). The role of polymer charge was assessed by infusions of neutral or sulphated dextran of average molecular mass 500 kDa (n = 6). When HA was present, Q̇s increased little with pressure, forming a virtual plateau of ∼4 μl min−1 from 10 to 25 cmH2O. Neutral dextran 2000 failed to replicate this effect. Instead, Q̇s increased steeply with Pj, reaching eight times the HA value by 20 cmH2O (P = 0.0001, ANOVA). Dextran 2000 reduced flows in comparison with Ringer solution. Analysis of the aspirated joint fluid showed that 31 ± 0.07 % (s.e.m.) of dextran 2000 in the filtrand was reflected by synovium, compared with ≥ 79 % for HA. The viscometric molecular radius of the dextran, ∼31 nm, was smaller than that of HA (101–181 nm), as was its osmotic pressure. Anionic dextran 500 failed to buffer fluid drainage, but it reduced fluid escape and synovial conductance dQ̇s/dPj more than neutral dextran 500 (P < 0.0001, ANOVA). The anionic charge increased the molecular volume and viscosity of dextran 500. The results support the hypothesis that polymer molecular volume influences its reflection by interstitial matrix and outflow buffering. Polymer charge influences flow through an effect on viscosity and possibly electrostatic interactions with negatively charged interstitial matrix. PMID:11060134

A simple model of fluid flow and electrolyte balance in the body

NASA Technical Reports Server (NTRS)

White, R. J.; Neal, L.

1973-01-01

The model is basically a three-compartment model, the three compartments being the plasma, interstitial fluid and cellular fluid. Sodium, potassium, chloride and urea are the only major solutes considered explicitly. The control of body water and electrolyte distribution is affected via drinking and hormone levels. Basically, the model follows the effect of various oral input water loads on solute and water distribution throughout the body.

Myofibroblasts in interstitial lung diseases show diverse electron microscopic and invasive features.

PubMed

Karvonen, Henna M; Lehtonen, Siri T; Sormunen, Raija T; Harju, Terttu H; Lappi-Blanco, Elisa; Bloigu, Risto S; Kaarteenaho, Riitta L

2012-09-01

The characteristic features of myofibroblasts in various lung disorders are poorly understood. We have evaluated the ultrastructure and invasive capacities of myofibroblasts cultured from small volumes of diagnostic bronchoalveolar lavage (BAL) fluid samples from patients with different types of lung diseases. Cells were cultured from samples of BAL fluid collected from 51 patients that had undergone bronchoscopy and BAL for diagnostic purposes. The cells were visualized by transmission electron microscopy and immunoelectron microscopy to achieve ultrastructural localization of alpha-smooth muscle actin (α-SMA) and fibronectin. The levels of α-SMA protein and mRNA and fibronectin mRNA were measured by western blot and quantitative real-time reverse transcriptase polymerase chain reaction. The invasive capacities of the cells were evaluated. The cultured cells were either fibroblasts or myofibroblasts. The structure of the fibronexus, and the amounts of intracellular actin, extracellular fibronectin and cell junctions of myofibroblasts varied in different diseases. In electron and immunoelectron microscopy, cells cultured from interstitial lung diseases (ILDs) expressed more actin filaments and α-SMA than normal lung. The invasive capacity of the cells obtained from patients with idiopathic pulmonary fibrosis was higher than that from patients with other type of ILDs. Cells expressing more actin filaments had a higher invasion capacity. It is concluded that electron and immunoelectron microscopic studies of myofibroblasts can reveal differential features in various diseases. An analysis of myofibroblasts cultured from diagnostic BAL fluid samples may represent a new kind of tool for diagnostics and research into lung diseases.

Interaction between blood-brain barrier and glymphatic system in solute clearance.

PubMed

Verheggen, I C M; Van Boxtel, M P J; Verhey, F R J; Jansen, J F A; Backes, W H

2018-03-30

Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The role of the extracellular matrix in tissue distribution of macromolecules in normal and pathological tissues: potential therapeutic consequences.

PubMed

Wiig, Helge; Gyenge, Christina; Iversen, Per Ole; Gullberg, Donald; Tenstad, Olav

2008-05-01

The interstitial space is a dynamic microenvironment that consists of interstitial fluid and structural molecules of the extracellular matrix, such as glycosaminoglycans (hyaluronan and proteoglycans) and collagen. Macromolecules can distribute in the interstitium only in those spaces unoccupied by structural components, a phenomenon called interstitial exclusion. The exclusion phenomenon has direct consequences for plasma volume regulation. Early studies have assigned a major role to collagen as an excluding agent that accounts for the sterical (geometrical) exclusion. More recently, it has been shown that the contribution of negatively charged glycosaminoglycans might also be significant, resulting in an additional electrostatical exclusion effect. This charge effect may be of importance for drug uptake and suggests that either the glycosaminoglycans or the net charge of macromolecular substances to be delivered may be targeted to increase the available volume and uptake of macromolecular therapeutic agents in tumor tissue. Here, we provide an overview of the structural components of the interstitium and discuss the importance the sterical and electrostatical components have on the dynamics of transcapillary fluid exchange.

Combined aliskiren and amlodipine reduce albuminuria via reduction in renal inflammation in diabetic rats.

PubMed

Matavelli, Luis C; Huang, Jiqian; Siragy, Helmy M

2012-03-01

We hypothesized that compared with hydrochlorothiazide (HCTZ), the renin inhibitor aliskiren (ALISK) or amlodipine (AMLO) and their combination reduce albuminuria via reduction in renal inflammation, independent of blood pressure (BP) changes. We studied normal and streptozotocin-induced diabetic (DM) Sprague-Dawley rats treated for 6 weeks with vehicle, ALISK, HCTZ, or AMLO individually and combined and evaluated the effects of treatments on BP, urine albumin to creatinine ratio, renal interstitial fluid levels of angiotensin II, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) and renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B. There were no differences in BP between treatments. Only ALISK and its combinations reduced renal interstitial fluid angiotensin II. Urine albumin to creatinine ratio increased in DM rats and decreased with ALISK alone or combined with HCTZ or AMLO. HCTZ or AMLO individually and combined did not influence urine albumin to creatinine ratio. Renal interstitial fluid TNF-α and IL-6, and the renal expression of TNF-α, IL-6, transforming growth factor beta 1, and nuclear factor kappa B were increased in DM rats. These renal inflammatory markers were reduced only with ALISK or AMLO individually or combined with other treatments. We conclude that ALISK alone and combined with HCTZ or AMLO reduced albuminuria in diabetes via reduction in renal inflammation, independent of BP changes.

Determination of (2)H-enrichment of rat brain interstitial fluid and rat plasma by headspace-gas-chromatography - quadrupole-mass-spectrometry.

PubMed

Eberl, Anita; Altendorfer-Kroath, Thomas; Kollmann, Denise; Birngruber, Thomas; Sinner, Frank; Raml, Reingard; Magnes, Christoph

2016-09-15

(2)H2O as nonradioactive, stable marker substance is commonly used in preclinical and clinical studies and the precise determination of (2)H2O concentration in biological samples is crucial. However, aside from isotope ratio mass spectrometry (IRMS), only a very limited number of methods to accurately measure the (2)H2O concentration in biological samples are routinely established until now. In this study, we present a straightforward method to accurately measure (2)H-enrichment of rat brain interstitial fluid (ISF) and rat plasma to determine the relative recovery of a cerebral open flow microperfusion (cOFM) probe, using headspace-gas-chromatography - quadrupole-mass-spectrometry. This method is based on basic-catalyzed hydrogen/deuterium exchange in acetone and detects the (2)H-labelled acetone directly by the headspace GC-MS. Small sample volumes and limited number of preparation steps make this method highly competitive. It has been fully validated. (2)H enriched to 8800 ppm in plasma showed an accuracy of 98.9% and %Relative Standard Deviation (RSD) of 3.1 with n = 18 over three days and with two operators. Similar performance was obtained for cerebral ISF enriched to 1100 ppm (accuracy: 96.5%, %RSD: 3.1). With this highly reproducible method we demonstrated the successful employment of (2)H2O as performance marker for a cOFM probe. Copyright © 2016. Published by Elsevier Inc.

Fluid Volume Overload and Congestion in Heart Failure: Time to Reconsider Pathophysiology and How Volume Is Assessed.

PubMed

Miller, Wayne L

2016-08-01

Volume regulation, assessment, and management remain basic issues in patients with heart failure. The discussion presented here is directed at opening a reassessment of the pathophysiology of congestion in congestive heart failure and the methods by which we determine volume overload status. Peer-reviewed historical and contemporary literatures are reviewed. Volume overload and fluid congestion remain primary issues for patients with chronic heart failure. The pathophysiology is complex, and the simple concept of intravascular fluid accumulation is not adequate. The dynamics of interstitial and intravascular fluid compartment interactions and fluid redistribution from venous splanchnic beds to central pulmonary circulation need to be taken into account in strategies of volume management. Clinical bedside evaluations and right heart hemodynamic assessments can alert clinicians of changes in volume status, but only the quantitative measurement of total blood volume can help identify the heterogeneity in plasma volume and red blood cell mass that are features of volume overload in patients with chronic heart failure and help guide individualized, appropriate therapy-not all volume overload is the same. © 2016 American Heart Association, Inc.

Inter-laboratory validation of bioaccessibility testing for metals.

PubMed

Henderson, Rayetta G; Verougstraete, Violaine; Anderson, Kim; Arbildua, José J; Brock, Thomas O; Brouwers, Tony; Cappellini, Danielle; Delbeke, Katrien; Herting, Gunilla; Hixon, Greg; Odnevall Wallinder, Inger; Rodriguez, Patricio H; Van Assche, Frank; Wilrich, Peter; Oller, Adriana R

2014-10-01

Bioelution assays are fast, simple alternatives to in vivo testing. In this study, the intra- and inter-laboratory variability in bioaccessibility data generated by bioelution tests were evaluated in synthetic fluids relevant to oral, inhalation, and dermal exposure. Using one defined protocol, five laboratories measured metal release from cobalt oxide, cobalt powder, copper concentrate, Inconel alloy, leaded brass alloy, and nickel sulfate hexahydrate. Standard deviations of repeatability (sr) and reproducibility (sR) were used to evaluate the intra- and inter-laboratory variability, respectively. Examination of the sR:sr ratios demonstrated that, while gastric and lysosomal fluids had reasonably good reproducibility, other fluids did not show as good concordance between laboratories. Relative standard deviation (RSD) analysis showed more favorable reproducibility outcomes for some data sets; overall results varied more between- than within-laboratories. RSD analysis of sr showed good within-laboratory variability for all conditions except some metals in interstitial fluid. In general, these findings indicate that absolute bioaccessibility results in some biological fluids may vary between different laboratories. However, for most applications, measures of relative bioaccessibility are needed, diminishing the requirement for high inter-laboratory reproducibility in absolute metal releases. The inter-laboratory exercise suggests that the degrees of freedom within the protocol need to be addressed. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique.

PubMed

Johannsen, M; Gneveckow, U; Eckelt, L; Feussner, A; Waldöfner, N; Scholz, R; Deger, S; Wust, P; Loening, S A; Jordan, A

2005-11-01

The aim of this pilot study was to evaluate whether the technique of magnetic fluid hyperthermia can be used for minimally invasive treatment of prostate cancer. This paper presents the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated while rectum and urethra were spared. Nanoparticle suspensions were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans, using an alternating current magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA m(-1)). Invasive thermometry of the prostate was carried out in the first and last of six weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks. Using appropriate software (AMIRA), a non-invasive estimation of temperature values in the prostate, based on intra-tumoural distribution of magnetic nanoparticles, can be performed and correlated with invasively measured intra-prostatic temperatures. Using a specially designed cooling device, treatment was well tolerated without anaesthesia. In the first patient treated, maximum and minimum intra-prostatic temperatures measured at a field strength of 4.0-5.0 kA m(-1) were 48.5 degrees C and 40.0 degrees C during the 1st treatment and 42.5 degrees C and 39.4 degrees C during the 6th treatment, respectively. These first clinical experiences prompted us to initiate a phase I study to evaluate feasibility, toxicity and quality of life during hyperthermia using magnetic nanoparticles in patients with biopsy-proven local recurrence of prostate cancer following radiotherapy with curative intent. To the authors' knowledge, this is the first report on clinical application of interstitial hyperthermia using magnetic nanoparticles in the treatment of human cancer.

Textural versus electrostatic exclusion-enrichment effects in the effective chemical transport within the cortical bone: a numerical investigation.

PubMed

Lemaire, T; Kaiser, J; Naili, S; Sansalone, V

2013-11-01

Interstitial fluid within bone tissue is known to govern the remodelling signals' expression. Bone fluid flow is generated by skeleton deformation during the daily activities. Due to the presence of charged surfaces in the bone porous matrix, the electrochemical phenomena occurring in the vicinity of mechanosensitive bone cells, the osteocytes, are key elements in the cellular communication. In this study, a multiscale model of interstitial fluid transport within bone tissues is proposed. Based on an asymptotic homogenization method, our modelling takes into account the physicochemical properties of bone tissue. Thanks to this multiphysical approach, the transport of nutrients and waste between the blood vessels and the bone cells can be quantified to better understand the mechanotransduction of bone remodelling. In particular, it is shown that the electrochemical tortuosity may have stronger implications in the mass transport within the bone than the purely morphological one. Copyright © 2013 John Wiley & Sons, Ltd.

Pneumocystis Jiroveci Pneumonia

DTIC Science & Technology

2008-10-01

patients with AIDS include CMV pneumonia, lymphocytic interstitial pneumonia, MAI infection, cryptococcal infection, Legionella , Mycoplasma...negative for Legionella , Streptococcus pneumoniae, and Cryptococcus neoformans. Pneumocystis direct fluorescent antibody (DFA) of the fluid was also

Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy.

PubMed

Lo Gullo, Roberto; Mishra, Shelly; Lira, Diego A; Padole, Atul; Otrakji, Alexi; Khawaja, Ranish Deedar Ali; Pourjabbar, Sarvenaz; Singh, Sarabjeet; Shepard, Jo-Anne O; Digumarthy, Subba R; Kalra, Mannudeep K; Stone, James R

2015-12-01

Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca.

High-intensity intermittent exercise increases pulmonary interstitial edema at altitude but not at simulated altitude.

PubMed

Edsell, Mark E; Wimalasena, Yashvi H; Malein, William L; Ashdown, Kimberly M; Gallagher, Carla A; Imray, Chris H; Wright, Alex D; Myers, Stephen D

2014-12-01

Ascent to high altitude leads to a reduction in ambient pressure and a subsequent fall in available oxygen. The resulting hypoxia can lead to elevated pulmonary artery (PA) pressure, capillary stress, and an increase in interstitial fluid. This fluid can be assessed on lung ultrasound (LUS) by the presence of B-lines. We undertook a chamber and field study to assess the impact of high-intensity exercise in hypoxia on the development of pulmonary interstitial edema in healthy lowlanders. Thirteen volunteers completed a high-intensity intermittent exercise (HIIE) test at sea level, in acute normobaric hypoxia (12% O2, approximately 4090 m equivalent altitude), and in hypobaric hypoxia during a field study at 4090 m after 6 days of acclimatization. Pulmonary interstitial edema was assessed by the evaluation of LUS B-lines. After HIIE, no increase in B-lines was seen in normoxia, and a small increase was seen in acute normobaric hypoxia (2 ± 2; P < .05). During the field study at 4090 m, 12 participants (92%) demonstrated 7 ± 4 B-lines at rest, which increased to 17 ± 5 immediately after the exercise test (P < .001). An increase was evident in all participants. There was a reciprocal fall in peripheral arterial oxygen saturations (Spo2) after exercise from 88% ± 4% to 80% ± 8% (P < .01). B-lines and Spo2 in all participants returned to baseline levels within 4 hours. HIIE led to an increase in B-lines at altitude after subacute exposure but not during acute exposure at equivalent simulated altitude. This may indicate pulmonary interstitial edema. Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.; Mendonca, Margarida M.

1995-01-01

Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days heat-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.

Direct Evidence of Acetaminophen Interference with Subcutaneous Glucose Sensing in Humans: A Pilot Study

PubMed Central

Basu, Ananda; Veettil, Sona; Dyer, Roy; Peyser, Thomas

2016-01-01

Abstract Background: Recent advances in accuracy and reliability of continuous glucose monitoring (CGM) devices have focused renewed interest on the use of such technology for therapeutic dosing of insulin without the need for independent confirmatory blood glucose meter measurements. An important issue that remains is the susceptibility of CGM devices to erroneous readings in the presence of common pharmacologic interferences. We report on a new method of assessing CGM sensor error to pharmacologic interferences using the example of oral administration of acetaminophen. Materials and Methods: We examined the responses of several different Food and Drug Administration–approved and commercially available CGM systems (Dexcom [San Diego, CA] Seven® Plus™, Medtronic Diabetes [Northridge, CA] Guardian®, and Dexcom G4® Platinum) to oral acetaminophen in 10 healthy volunteers without diabetes. Microdialysis catheters were placed in the abdominal subcutaneous tissue. Blood and microdialysate samples were collected periodically and analyzed for glucose and acetaminophen concentrations before and after oral ingestion of 1 g of acetaminophen. We compared the response of CGM sensors with the measured acetaminophen concentrations in the blood and interstitial fluid. Results: Although plasma glucose concentrations remained constant at approximately 90 mg/dL (approximately 5 mM) throughout the study, CGM glucose measurements varied between approximately 85 to 400 mg/dL (from approximately 5 to 22 mM) due to interference from the acetaminophen. The temporal profile of CGM interference followed acetaminophen concentrations measured in interstitial fluid (ISF). Conclusions: This is the first direct measurement of ISF concentrations of putative CGM interferences with simultaneous measurements of CGM performance in the presence of the interferences. The observed interference with glucose measurements in the tested CGM devices coincided temporally with appearance of acetaminophen in the ISF. The method applied here can be used to determine the susceptibility of current and future CGM systems to interference from acetaminophen or other exogenous pharmacologic agents. PMID:26784129

Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors

PubMed Central

2014-01-01

Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection. PMID:24987457

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

PubMed Central

Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T.; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge

2015-01-01

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. PMID:26077718

A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.

PubMed

Aspelund, Aleksanteri; Antila, Salli; Proulx, Steven T; Karlsen, Tine Veronica; Karaman, Sinem; Detmar, Michael; Wiig, Helge; Alitalo, Kari

2015-06-29

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease. © 2015 Aspelund et al.

Effects of coarse grain size distribution and fine particle content on pore fluid pressure and shear behavior in experimental debris flows

NASA Astrophysics Data System (ADS)

Kaitna, Roland; Palucis, Marisa C.; Yohannes, Bereket; Hill, Kimberly M.; Dietrich, William E.

2016-02-01

Debris flows are typically a saturated mixture of poorly sorted particles and interstitial fluid, whose density and flow properties depend strongly on the presence of suspended fine sediment. Recent research suggests that grain size distribution (GSD) influences excess pore pressures (i.e., pressure in excess of predicted hydrostatic pressure), which in turn plays a governing role in debris flow behaviors. We report a series of controlled laboratory experiments in a 4 m diameter vertically rotating drum where the coarse particle size distribution and the content of fine particles were varied independently. We measured basal pore fluid pressures, pore fluid pressure profiles (using novel sensor probes), velocity profiles, and longitudinal profiles of the flow height. Excess pore fluid pressure was significant for mixtures with high fines fraction. Such flows exhibited lower values for their bulk flow resistance (as measured by surface slope of the flow), had damped fluctuations of normalized fluid pressure and normal stress, and had velocity profiles where the shear was concentrated at the base of the flow. These effects were most pronounced in flows with a wide coarse GSD distribution. Sustained excess fluid pressure occurred during flow and after cessation of motion. Various mechanisms may cause dilation and contraction of the flows, and we propose that the sustained excess fluid pressures during flow and once the flow has stopped may arise from hindered particle settling and yield strength of the fluid, resulting in transfer of particle weight to the fluid. Thus, debris flow behavior may be strongly influenced by sustained excess fluid pressures controlled by particle settling rates.

Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy

PubMed Central

Yanamandra, Kiran; Patel, Tirth K.; Jiang, Hong; Schindler, Suzanne; Ulrich, Jason D.; Boxer, Adam L.; Miller, Bruce L.; Kerwin, Diana R.; Gallardo, Gilbert; Stewart, Floy; Finn, Mary Beth; Cairns, Nigel J.; Verghese, Philip B.; Fogelman, Ilana; West, Tim; Braunstein, Joel; Robinson, Grace; Keyser, Jennifer; Roh, Joseph; Knapik, Stephanie S.; Hu, Yan; Holtzman, David M.

2017-01-01

Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain. PMID:28424326

Modeling of heat transfer in a vascular tissue-like medium during an interstitial hyperthermia process.

PubMed

Hassanpour, Saeid; Saboonchi, Ahmad

2016-12-01

This paper aims to evaluate the role of small vessels in heat transfer mechanisms of a tissue-like medium during local intensive heating processes, for example, an interstitial hyperthermia treatment. To this purpose, a cylindrical tissue with two co- and counter-current vascular networks and a central heat source is introduced. Next, the energy equations of tissue, supply fluid (arterial blood), and return fluid (venous blood) are derived using porous media approach. Then, a 2D computer code is developed to predict the temperature of blood (fluid phase) and tissue (solid phase) by conventional volume averaging method and a more realistic solution method. In latter method, despite the volume averaging the blood of interconnect capillaries is separated from the arterial and venous blood phases. It is found that in addition to blood perfusion rate, the arrangement of vascular network has considerable effects on the pattern and amount of the achieved temperature. In contrast to counter-current network, the co-current network of vessels leads to considerable asymmetric pattern of temperature contours and relocation of heat affected zone along the blood flow direction. However this relocation can be prevented by changing the site of hyperthermia heat source. The results show that the cooling effect of co-current blood vessels during of interstitial heating is more efficient. Despite much anatomical dissimilarities, these findings can be useful in designing of protocols for hyperthermia cancer treatment of living tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement of lung fluid volumes and albumin exclusion in sheep

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

Pou, N.A.; Roselli, R.J.; Parker, R.E.

1989-10-01

A radioactive tracer technique was used to determine interstitial diethylenetriaminepentaacetic acid (DTPA) and albumin distribution volume in sheep lungs. {sup 125}I- and/or {sup 131}I-labeled albumin were injected intravenously and allowed to equilibrate for 24 h. {sup 99m}Tc-labeled DTPA and {sup 51}Cr-labeled erythrocytes were injected and allowed to equilibrate (2 h and 15 min, respectively) before a lethal dose of thiamylal sodium. Two biopsies (1-3 g) were taken from each lung and the remaining tissue was homogenized for wet-to-dry lung weight and volume calculations. Estimates of distribution volumes from whole lung homogenized samples were statistically smaller than biopsy samples for extravascularmore » water, interstitial {sup 99m}Tc-DTPA, and interstitial albumin. The mean fraction of the interstitium (Fe), which excludes albumin, was 0.68 +/- 0.04 for whole lung samples compared with 0.62 +/- 0.03 for biopsy samples. Hematocrit may explain the consistent difference. To make the Fe for biopsy samples match that for homogenized samples, a mean hematocrit, which was 82% of large vessel hematocrit, was required. Excluded volume fraction for exogenous sheep albumin was compared with that of exogenous human albumin in two sheep, and no difference was found at 24 h.« less

Hip chondrolabral mechanics during activities of daily living: Role of the labrum and interstitial fluid pressurization.

PubMed

Todd, Jocelyn N; Maak, Travis G; Ateshian, Gerard A; Maas, Steve A; Weiss, Jeffrey A

2018-03-01

Osteoarthritis of the hip can result from mechanical factors, which can be studied using finite element (FE) analysis. FE studies of the hip often assume there is no significant loss of fluid pressurization in the articular cartilage during simulated activities and approximate the material as incompressible and elastic. This study examined the conditions under which interstitial fluid load support remains sustained during physiological motions, as well as the role of the labrum in maintaining fluid load support and the effect of its presence on the solid phase of the surrounding cartilage. We found that dynamic motions of gait and squatting maintained consistent fluid load support between cycles, while static single-leg stance experienced slight fluid depressurization with significant reduction of solid phase stress and strain. Presence of the labrum did not significantly influence fluid load support within the articular cartilage, but prevented deformation at the cartilage edge, leading to lower stress and strain conditions in the cartilage. A morphologically accurate representation of collagen fibril orientation through the thickness of the articular cartilage was not necessary to predict fluid load support. However, comparison with simplified fibril reinforcement underscored the physiological importance. The results of this study demonstrate that an elastic incompressible material approximation is reasonable for modeling a limited number of cyclic motions of gait and squatting without significant loss of accuracy, but is not appropriate for static motions or numerous repeated motions. Additionally, effects seen from removal of the labrum motivate evaluation of labral reattachment strategies in the context of labral repair. Copyright © 2018 Elsevier Ltd. All rights reserved.

A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes.

PubMed

Sakaguchi, Kazuhiko; Hirota, Yushi; Hashimoto, Naoko; Ogawa, Wataru; Sato, Toshiyuki; Okada, Seiki; Hagino, Kei; Asakura, Yoshihiro; Kikkawa, Yasuo; Kojima, Junko; Maekawa, Yasunori; Nakajima, Hiromu

2012-06-01

Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.

Periodic Extraction of Interstitial Fluid from the Site of Subcutaneous Insulin Infusion for the Measurement of Glucose: A Novel Single-Port Technique for the Treatment of Type 1 Diabetes Patients

PubMed Central

Lindpointner, Stefan; Korsatko, Stefan; Tutkur, Dina; Bodenlenz, Manfred; Pieber, Thomas R.

2013-01-01

Abstract Background Treatment of type 1 diabetes patients could be simplified if the site of subcutaneous insulin infusion could also be used for the measurement of glucose. This study aimed to assess the agreement between blood glucose concentrations and glucose levels in the interstitial fluid (ISF) that is extracted from the insulin infusion site during periodic short-term interruptions of continuous subcutaneous insulin infusion (CSII). Subjects and Methods A perforated cannula (24 gauge) was inserted into subcutaneous adipose tissue of C-peptide-negative type 1 diabetes subjects (n=13) and used alternately to infuse rapid-acting insulin (100 U/mL) and to extract ISF glucose during a fasting period and after ingestion of a standard oral glucose load (75 g). Results Although periodically interrupted for extracting glucose (every hour for approximately 10 min), insulin infusion with the cannula was adequate to achieve euglycemia during fasting and to restore euglycemia after glucose ingestion. Furthermore, the ISF-derived estimates of plasma glucose levels agreed well with plasma glucose concentrations. Correlation coefficient and median absolute relative difference values were found to be 0.95 and 8.0%, respectively. Error grid analysis showed 99.0% of all ISF glucose values within clinically acceptable Zones A and B (83.5% Zone A, 15.5% Zone B). Conclusions Results show that ISF glucose concentrations measured at the insulin infusion site during periodic short-term interruptions of CSII closely reflect blood glucose levels, thus suggesting that glucose monitoring and insulin delivery may be performed alternately at the same tissue site. A single-port device of this type could be used to simplify and improve glucose management in diabetes. PMID:23126579

Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

PubMed

Foster, D M; Sylvester, H J; Papich, M G

2017-12-01

Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

Spleen and Lymphatic System (For Parents)

MedlinePlus

... they have many tiny openings that allow gases, water, and nutrients to pass through to the surrounding cells, nourishing them and taking away waste products. When lymph fluid leaks through in this way it is called interstitial ...

Fluid mechanics in the perivascular space.

PubMed

Wang, Peng; Olbricht, William L

2011-04-07

Perivascular space (PVS) within the brain is an important pathway for interstitial fluid (ISF) and solute transport. Fluid flowing in the PVS can affect these transport processes and has significant impacts on physiology. In this paper, we carry out a theoretical analysis to investigate the fluid mechanics in the PVS. With certain assumptions and approximations, we are able to find an analytical solution to the problem. We discuss the physical meanings of the solution and particularly examine the consequences of the induced fluid flow in the context of convection-enhanced delivery (CED). We conclude that peristaltic motions of the blood vessel walls can facilitate fluid and solute transport in the PVS. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of Biomarkers to Optimize Heat Acclimation in Women

DTIC Science & Technology

1996-10-01

that synthesis of HSP72 was induced in lymphocytes, spleen cells and soleus muscle after 20 min of exercise while rectal temperature elevated above 40...lethal temperatures for death due to nonexertionally and exertionally induced heat exhaustion, respectively (15). Upon completion of the exercise ...During exercise , interstitial fluid levels are reduced due to sweat formation and fluid shifts which tend to induce hypovolemia, compromising

Ultra-miniaturization of a planar amperometric sensor targeting continuous intradermal glucose monitoring.

PubMed

Ribet, Federico; Stemme, Göran; Roxhed, Niclas

2017-04-15

An ultra-miniaturized electrochemical biosensor for continuous glucose monitoring (CGM) is presented. The aim of this work is to demonstrate the possibility of an overall reduction in sensor size to allow minimally invasive glucose monitoring in the interstitial fluid in the dermal region, in contrast to larger state-of-the-art systems, which are necessarily placed in the subcutaneous layer. Moreover, the reduction in size might be a key factor to improve the stability and reliability of transdermal sensors, due to the reduction of the detrimental foreign body reaction and of consequent potential failures. These advantages are combined with lower invasiveness and discomfort for patients. The realized device consists of a microfabricated three-electrode enzymatic sensor with a total surface area of the sensing portion of less than 0.04mm 2 , making it the smallest fully integrated planar amperometric glucose sensor area reported to date. The working electrode and counter electrode consist of platinum and are functionalized by drop casting of three polymeric membranes. The on-chip iridium oxide (IrOx) pseudo-reference electrode provides the required stability for measurements under physiological conditions. The device is able to dynamically and linearly measure glucose concentrations in-vitro over the relevant physiological range, while showing sufficient selectivity to known interfering species present in the interstitial fluid, with resolution and sensitivity (1.51nA/mM) comparable to that of state-of-art commercial CGM systems. This work can therefore enable less invasive and improved CGM in patients affected by diabetes. Copyright © 2016 Elsevier B.V. All rights reserved.

Validation of oxygen extraction fraction measurement by qBOLD technique.

PubMed

He, Xiang; Zhu, Mingming; Yablonskiy, Dmitriy A

2008-10-01

Measurement of brain tissue oxygen extraction fraction (OEF) in both baseline and functionally activated states can provide important information on brain functioning in health and disease. The recently proposed quantitative BOLD (qBOLD) technique is MRI-based and provides a regional in vivo OEF measurement (He and Yablonskiy, MRM 2007, 57:115-126). It is based on a previously developed analytical BOLD model and incorporates prior knowledge about the brain tissue composition including the contributions from grey matter, white matter, cerebrospinal fluid, interstitial fluid and intravascular blood. The qBOLD model also allows for the separation of contributions to the BOLD signal from OEF and the deoxyhemoglobin containing blood volume (DBV). The objective of this study is to validate OEF measurements provided by the qBOLD approach. To this end we use a rat model and compare qBOLD OEF measurements against direct measurements of the blood oxygenation level obtained from venous blood drawn directly from the superior sagittal sinus. The cerebral venous oxygenation level of the rat was manipulated by utilizing different anestheisa methods. The study demonstrates a very good agreement between qBOLD approach and direct measurements. (c) 2008 Wiley-Liss, Inc.

Proteomic Characterization of Dermal Interstitial Fluid Extracted Using a Novel Microneedle-Assisted Technique.

PubMed

Tran, Bao Quoc; Miller, Philip R; Taylor, Robert M; Boyd, Gabrielle; Mach, Phillip M; Rosenzweig, C Nicole; Baca, Justin T; Polsky, Ronen; Glaros, Trevor

2018-01-05

As wearable fitness devices have gained commercial acceptance, interest in real-time monitoring of an individual's physiological status using noninvasive techniques has grown. Microneedles have been proposed as a minimally invasive technique for sampling the dermal interstitial fluid (ISF) for clinical monitoring and diagnosis, but little is known about its composition. In this study, a novel microneedle array was used to collect dermal ISF from three healthy human donors and compared with matching serum and plasma samples. Using a shotgun quantitative proteomic approach, 407 proteins were quantified with at least one unique peptide, and of those, 135 proteins were differently expressed at least 2-fold. Collectively, these proteins tended to originate from the cytoplasm, membrane bound vesicles, and extracellular vesicular exosomes. Proteomic analysis confirmed previously published work that indicates that ISF is highly similar to both plasma and serum. In this study, less than one percent of proteins were uniquely identified in ISF. Taken together, ISF could serve as a minimally invasive alternative for blood-derived fluids with potential for real-time monitoring applications.

Connective tissue of cervical carcinoma xenografts: associations with tumor hypoxia and interstitial fluid pressure and its assessment by DCE-MRI and DW-MRI.

PubMed

Hompland, Tord; Ellingsen, Christine; Galappathi, Kanthi; Rofstad, Einar K

2014-01-01

Abstract Background. A high fraction of stroma in malignant tissues is associated with tumor progression, metastasis, and poor prognosis. Possible correlations between the stromal and physiologic microenvironments of tumors and the potential of dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) in quantification of the stromal microenvironment were investigated in this study. Material and methods. CK-160 cervical carcinoma xenografts were used as preclinical tumor model. A total of 43 tumors were included in the study, and of these tumors, 17 were used to search for correlations between the stromal and physiologic microenvironments, 11 were subjected to DCE-MRI, and 15 were subjected to DW-MRI. DCE-MRI and DW-MRI were carried out at 1.5 T with a clinical MR scanner and a slotted tube resonator transceiver coil constructed for mice. Fraction of connective tissue (CTFCol) and fraction of hypoxic tissue (HFPim) were determined by immunohistochemistry. A Millar SPC 320 catheter was used to measure tumor interstitial fluid pressure (IFP). Results. CTFCol showed a positive correlation to IFP and an inverse correlation to HFPim. The apparent diffusion coefficient assessed by DW-MRI was inversely correlated to CTFCol, whereas no correlation was found between DCE-MRI-derived parameters and CTFCol. Conclusion. DW-MRI is a potentially useful method for characterizing the stromal microenvironment of tumors.

In vivo optical imaging of the viable epidermis around the nailfold capillaries for the assessment of heart failure severity in humans.

PubMed

Shirshin, Evgeny A; Gurfinkel, Yury I; Matskeplishvili, Simon T; Sasonko, Maria L; Omelyanenko, Nikolai P; Yakimov, Boris P; Lademann, Juergen; Darvin, Maxim E

2018-05-29

Heart failure is among the socially significant diseases, involving over 2% of the adult population in the developed countries. Diagnostics of the HF severity remains complicated due to the absence of specific symptoms and objective criteria. Here we present an indicator of the HF severity based on the imaging tissue parameters around the nailfold capillaries. High resolution nailfold video capillaroscopy was performed to determine the perivascular zone (PZ) size around nailfold capillaries, and two-photon tomography with fluorescence lifetime imaging was used to investigate PZ composition. We found that the size of PZ around the nailfold capillaries strongly correlates with heart failure severity. Further investigations using two-photon tomography demonstrated that PZ corresponds to the border of viable epidermis and it was suggested that the PZ size variations were due to the different amounts of interstitial fluid that potentially further translates in clinically significant oedema. The obtained results allow for the development of a quantitative indicator of oedematous syndrome, which can be used in various applications to monitor the dynamics of interstitial fluid retention. We therefore suggest PZ size measured with nailfold video capillaroscopy as a novel quantitative sensitive non-invasive marker of heart failure severity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Susceptibility of interstitial continuous glucose monitor performance to sleeping position.

PubMed

Mensh, Brett D; Wisniewski, Natalie A; Neil, Brian M; Burnett, Daniel R

2013-07-01

Developing a round-the-clock artificial pancreas requires accurate and stable continuous glucose monitoring. The most widely used continuous glucose monitors (CGMs) are percutaneous, with the sensor residing in the interstitial space. Inaccuracies in percutaneous CGM readings during periods of lying on the devices (e.g., in various sleeping positions) have been anecdotally reported but not systematically studied. In order to assess the impact of sleep and sleep position on CGM performance, we conducted a study in human subjects in which we measured the variability of interstitial CGM data at night as a function of sleeping position. Commercially available sensors were placed for 4 days in the abdominal subcutaneous tissue in healthy, nondiabetic volunteers (four sensors per person, two per side). Nocturnal sleeping position was determined from video recordings and correlated to sensor data. We observed that, although the median of the four sensor readings was typically 70-110 mg/dl during sleep, individual sensors intermittently exhibited aberrant glucose readings (>25 mg/dl away from median) and that these aberrant readings were strongly correlated with subjects lying on the sensors. We expected and observed that most of these aberrant sleep-position-related CGM readings were sudden decreases in reported glucose values, presumably due to local blood-flow decreases caused by tissue compression. Curiously, in rare cases, the aberrant CGM readings were elevated values. These findings highlight limitations in our understanding of interstitial fluid physiology in the subcutaneous space and have significant implications for the utilization of sensors in the construction of an artificial pancreas. © 2013 Diabetes Technology Society.

Clinical utility of capillary polymerase chain reaction for diagnosis of Cytomegalovirus pneumonia.

PubMed

Honda, J; Yonemitsu, J; Kitajima, H; Yosida, N; Fumirori, T; Oizumi, K

2001-01-01

The purpose of this retrospective study was to assess the diagnostic efficacy of CMV DNA detection by capillary PCR in patients with interstitial pneumonia. Of 882 samples taken from 363 patients, 317 were obtained from sputum, 94 from BAL fluid, 291 from blood and 180 from urine. PCR for CMV was positive in 58 samples (6.6%), with positive detection for 6.9% of sputum, 10.6% of BAL fluid, 4.1% of blood and 7.8% of urine samples. CMV pneumonia was diagnosed retrospectively in 34 (9.4%) of the 363 patients by demonstration of CMV antigen-positive cytomegalic inclusion bodies in lung tissue sections. The positive and negative predictive values were 100% (10/10) and 98.8% (83/84) for the BAL fluid samples and 95.5% (21/22) and 99.7% (294/295) for the sputum samples, respectively. Clinical sensitivity and specificity were 90.9% (10/11) and 100% (83/83) for the BAL fluid samples and 95.5% (21/22) and 99.7% (294/295) for the sputum samples, respectively. However, the blood and urine samples showed poor clinical sensitivity and low positive predictive values. We suggest that the use of capillary PCR for BAL fluid and sputum samples is very useful for diagnosing CMV pneumonia in patients with interstitial pneumonia in whom CMV pneumonia is suspected.

Insulin transport into the brain.

PubMed

Gray, Sarah M; Barrett, Eugene J

2018-05-30

While there is a growing consensus that insulin has diverse and important regulatory actions on the brain, seemingly important aspects of brain insulin physiology are poorly understood. Examples include: what is the insulin concentration within brain interstitial fluid under normal physiologic conditions; whether insulin is made in the brain and acts locally; does insulin from the circulation cross the blood-brain barrier or the blood-CSF barrier in a fashion that facilitates its signaling in brain; is insulin degraded within the brain; do privileged areas with a "leaky" blood-brain barrier serve as signaling nodes for transmitting peripheral insulin signaling; does insulin action in the brain include regulation of amyloid peptides; whether insulin resistance is a cause or consequence of processes involved in cognitive decline. Heretofore, nearly all studies examining brain insulin physiology have employed techniques and methodologies that do not appreciate the complex fluid compartmentation and flow throughout the brain. This review attempts to provide a status report on historical and recent work that begins to address some of these issues. It is undertaken in an effort to suggest a framework for studies going forward. Such studies are inevitably influenced by recent physiologic and genetic studies of insulin accessing and acting in brain, discoveries relating to brain fluid dynamics and the interplay of cerebrospinal fluid, brain interstitial fluid, and brain lymphatics, and advances in clinical neuroimaging that underscore the dynamic role of neurovascular coupling.

A model of fluid and solute exchange in the human: validation and implications.

PubMed

Bert, J L; Gyenge, C C; Bowen, B D; Reed, R K; Lund, T

2000-11-01

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Interstitial water studies on small core samples, Deep Sea Drilling Project, Leg 6

USGS Publications Warehouse

Manheim, F. T.; Sayles, F.L.

1971-01-01

Sediments from Leg 6 sites, west of the Hawaiian Islands, consisted primarily of various combinations of deep-sea biogenic oozes, volcanic ash, and its breakdown products. Pore fluids from most of the sites were similar in composition to present day ocean water, and in some sties almost identical. However, interstitial fluids from Site 53 (Philippine Sea) showed changes in ionic composition which were beyond those previously considered attributable to diagenetic influence. These samples show the beginnings of metamorphism by dramatic increases in calcium concentrations and corresponding decreases in alkali concentrations. Analytical methods were similar to those outlined in previous Leg Reports. However, obvious contamination of aliquots for sodium determination in the laboratory made it necessary to determine all sodium values by difference between anion and cation balances. These values are, if anything, more accurate than direct determinations which have been discussed in earlier legs. However, the authors will continue to analyze sodium directly, and in the future they may be able to improve the precision of the determinations to the point where small losses and gains of sodium in the pore fluids may be established accurately. Agreement between colorimetric and spectrometric determinations of silicon has improved, but there are still occasional marked differences for which the writers have no explanation. T. Takahashi has allowed the authors to compare total Carbon Dioxide (CO2) measurements from his laboratory with their alkalinity determinations: both sets of data were obtained from fluids from the same squeezings of sediments and should give similar values at the indicated pH levels. Some disturbingly large discrepancies in the two sets of data are evident. The authors do not think that their back-titration alkalinity technique alone is responsible for the differences. However, they have not evaluated the possible influence of the heat-sealed polyethylene pipes on the alkalinity values; this should be considered a potential source of error. The pH data from water samples processed and measured on shipboard are reported here. In view of the major changes in pressure and temperature (laboratory temperatures were reported to be 26 to 28°C) and the sediments to new gaseous regimes prior to pH measurement, these values should be interpreted mainly as applying to the squeezed effluents, not to in situ values.

Cold-induced fluid extravasation during cardiopulmonary bypass in piglets can be counteracted by use of iso-oncotic prime.

PubMed

Farstad, Marit; Kvalheim, Venny Lise; Husby, Paul

2005-08-01

Hypothermic cardiopulmonary bypass is associated with increased fluid extravasation. This study aimed to compare whether iso-oncotic priming solutions, in contrast to crystalloids, could reduce the cold-induced fluid extravasation during cardiopulmonary bypass in piglets. Three groups were studied: the control group (CT group; n = 10), the albumin group (Alb group; n = 7), and the hydroxyethyl starch group (HES group; n = 7). Prime (1000 mL) and supplemental fluid were acetated Ringer solution, 4% albumin, and 6% hydroxyethyl starch, respectively. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (cooling to 28 degrees C within 15 minutes) was initiated and continued to 90 minutes. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit levels, and tissue water content were recorded, and protein masses and fluid extravasation rates were calculated. Colloid osmotic pressure in plasma decreased immediately after the start of cardiopulmonary bypass in the CT group but remained stable in the Alb and HES groups. Colloid osmotic pressure in interstitial fluid tended to decrease in the CT group and remained unchanged in the Alb group, whereas a slight increase was observed in the HES group. Immediately after the start of cooling, fluid extravasation rates increased from 0.15 +/- 0.10 to 0.64 +/- 0.12 mL . kg -1 . min -1 in the CT group, whereas no such increase was observed in the Alb and HES groups. The changes in fluid extravasation rates were reflected by corresponding changes in tissue water content. The use of albumin or hydroxyethyl starch as prime to preserve the colloid osmotic pressure during cardiopulmonary bypass causes a reduction in the cold-induced fluid extravasation compared with that seen with crystalloids. Albumin seems more effective than hydroxyethyl starch to limit cold-induced fluid shifts during cardiopulmonary bypass.

The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future.

PubMed

Plog, Benjamin A; Nedergaard, Maiken

2018-01-24

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters the brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed.

The glymphatic system in CNS health and disease: past, present and future

PubMed Central

Plog, Benjamin A.; Nedergaard, Maiken

2018-01-01

The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

Hierarchical poroelasticity: movement of interstitial fluid between porosity levels in bones.

PubMed

Cowin, Stephen C; Gailani, Gaffar; Benalla, Mohammed

2009-09-13

The governing equations for the theory of poroelastic materials with hierarchical pore space architecture and compressible constituents undergoing small deformations are developed. These equations are applied to the problem of determining the exchange of pore fluid between the vascular porosity (PV) and the lacunar-canalicular porosity (PLC) in bone tissue due to cyclic mechanical loading and blood pressure oscillations. The result is basic to the understanding of interstitial flow in bone tissue that, in turn, is basic to understanding of nutrient transport from the vasculature to the bone cells buried in the bone tissue and to the process of mechanotransduction by these cells. A formula for the volume of fluid that moves between the PLC and PV in a cyclic loading is obtained as a function of the cyclic mechanical loading and blood pressure oscillations. Formulas for the oscillating fluid pore pressure in both the PLC and the PV are obtained as functions of the two driving forces, the cyclic mechanical straining and the blood pressure, both with specified amplitude and frequency. The results of this study also suggest a PV permeability greater than 10(-9) m(2) and perhaps a little lower than 10(-8) m(2). Previous estimates of this permeability have been as small as 10(-14) m(2).

Characterization of the liver tissue interstitial fluid (TIF) proteome indicates potential for application in liver disease biomarker discovery.

PubMed

Sun, Wei; Ma, Jie; Wu, Songfeng; Yang, Dong; Yan, Yujuan; Liu, Kehui; Wang, Jinglan; Sun, Longqin; Chen, Ning; Wei, Handong; Zhu, Yunping; Xing, Baocai; Zhao, Xiaohang; Qian, Xiaohong; Jiang, Ying; He, Fuchu

2010-02-05

Tissue interstitial fluid (TIF) forms the interface between circulating body fluids and intracellular fluid. Pathological alterations of liver cells could be reflected in TIF, making it a promising source of liver disease biomarkers. Mouse liver TIF was extracted, separated by SDS-PAGE, analyzed by linear ion trap mass spectrometer, and 1450 proteins were identified. These proteins may be secreted, shed from membrane vesicles, or represent cellular breakdown products. They show different profiling patterns, quantities, and possibly modification/cleavage of intracellular proteins. The high solubility and even distribution of liver TIF supports its suitability for proteome analysis. Comparison of mouse liver TIF data with liver tissue and plasma proteome data identified major proteins that might be released from liver to plasma and serve as blood biomarkers of liver origin. This result was partially supported by comparison of human liver TIF data with human liver and plasma proteome data. Paired TIFs from tumor and nontumor liver tissues of a hepatocellular carcinoma patient were analyzed and the profile of subtracted differential proteins supports the potential for biomarker discovery in TIF. This study is the first analysis of the liver TIF proteome and provides a foundation for further application of TIF in liver disease biomarker discovery.

An analytical poroelastic model for ultrasound elastography imaging of tumors

NASA Astrophysics Data System (ADS)

Tauhidul Islam, Md; Chaudhry, Anuj; Unnikrishnan, Ginu; Reddy, J. N.; Righetti, Raffaella

2018-01-01

The mechanical behavior of biological tissues has been studied using a number of mechanical models. Due to the relatively high fluid content and mobility, many biological tissues have been modeled as poroelastic materials. Diseases such as cancers are known to alter the poroelastic response of a tissue. Tissue poroelastic properties such as compressibility, interstitial permeability and fluid pressure also play a key role for the assessment of cancer treatments and for improved therapies. At the present time, however, a limited number of poroelastic models for soft tissues are retrievable in the literature, and the ones available are not directly applicable to tumors as they typically refer to uniform tissues. In this paper, we report the analytical poroelastic model for a non-uniform tissue under stress relaxation. Displacement, strain and fluid pressure fields in a cylindrical poroelastic sample containing a cylindrical inclusion during stress relaxation are computed. Finite element simulations are then used to validate the proposed theoretical model. Statistical analysis demonstrates that the proposed analytical model matches the finite element results with less than 0.5% error. The availability of the analytical model and solutions presented in this paper may be useful to estimate diagnostically relevant poroelastic parameters such as interstitial permeability and fluid pressure, and, in general, for a better interpretation of clinically-relevant ultrasound elastography results.

Laboratory Experiments Modelling Sediment Transport by River Plumes

NASA Astrophysics Data System (ADS)

Sutherland, Bruce; Gingras, Murray; Knudson, Calla; Steverango, Luke; Surma, Chris

2016-11-01

Through lock-release laboratory experiments, the transport of particles by hypopycnal (surface) currents is examined as they flow into a uniform-density and a two-layer ambient fluid. In most cases the tank is tilted so that the current flows over a slope representing an idealization of a sediment-bearing river flowing into the ocean and passing over the continental shelf. When passing into a uniform-density ambient, the hypopycnal current slows and stops as particles rain out, carrying some of the light interstitial fluid with them. Rather than settling on the bottom, in many cases the descending particles accumulate to form a hyperpycnal (turbidity) current that flows downslope. This current then slows and stops as particles both rain out to the bottom and also rise again to the surface, carried upward by the light interstitial fluid. For a hypopycnal current flowing into a two-layer fluid, the current slows as particles rain out and accumulate at the interface of the two-layer ambient. Eventually these particles penetrate through the interface and settle to the bottom with no apparent formation of a hyperpycnal current. Analyses are performed to characterize the speed of the currents and stopping distances as they depend upon experiment parameters. Natural Sciences and Engineering Research Council.

Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress.

PubMed

Triacca, Valentina; Güç, Esra; Kilarski, Witold W; Pisano, Marco; Swartz, Melody A

2017-04-28

The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell-cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport. The aim of this study was to determine the relative importance of transcellular (vesicular) versus paracellular transport pathways by LECs and how mechanical stress (ie, fluid flow conditioning) alters either pathway. We demonstrate that transcellular transport mechanisms substantially contribute to lymphatic solute transport and that solute uptake occurs in both caveolae- and clathrin-coated vesicles. In vivo, intracelluar uptake of fluorescently labeled albumin after intradermal injection by LECs was similar to that of dermal dendritic cells. In vitro, we developed a method to differentially quantify intracellular solute uptake versus transendothelial transport by LECs. LECs preconditioned to 1 µm/s transmural flow demonstrated increased uptake and basal-to-apical solute transport, which could be substantially reversed by blocking dynamin-dependent vesicle formation. These findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues. © 2017 American Heart Association, Inc.

Ultrasound features of purulent skin and soft tissue infection without abscess.

PubMed

Nelson, Courtney E; Chen, Aaron E; Bellah, Richard D; Biko, David M; Ho-Fung, Victor M; Francavilla, Michael L; Xiao, Rui; Kaplan, Summer L

2018-06-06

Ultrasound (US) aids clinical management of skin and soft tissue infection (SSTI) by differentiating non-purulent cellulitis from abscess. However, purulent SSTI may be present without abscess. Guidelines recommend incision and drainage (I & D) for purulent SSTI, but US descriptions of purulent SSTI without abscess are lacking. We retrospectively reviewed pediatric emergency department patients with US of the buttock read as negative for abscess. We identified US features of SSTI with adequate interobserver agreement (kappa > 0.45). Six independent observers then ranked presence or absence of these features on US exams. We studied association between US features and positive wound culture using logistic regression models (significance at p < 0.05). Of 217 children, 35 patients (16%) had cultures positive for pathogens by 8 h after US and 61 patients (32%) had cultures positive by 48 h after US. We found kappa > 0.45 for focal collection > 1.0 cm (κ = 0.57), hyperemia (κ = 0.57), swirling with compression (κ = 0.52), posterior acoustic enhancement (κ = 0.47), and cobblestoning or branching interstitial fluid (κ = 0.45). Only cobblestoning or interstitial fluid was associated with positive wound cultures in logistic regression models at 8 and 48 h. Cobblestoning or interstitial fluid on US may indicate presence of culture-positive, purulent SSTI in patients without US appearance of abscess. Although our study has limitations due to its retrospective design, this US appearance should alert imagers that the patient may benefit from early I & D.

Increased alveolar plasminogen activator in early asbestosis

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

Cantin, A.; Allard, C.; Begin, R.

1989-03-01

Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS)more » or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.« less

Phytate (IP6) is a powerful agent for preventing calcifications in biological fluids: usefulness in renal lithiasis treatment.

PubMed

Grases, F; Costa-Bauzá, A

1999-01-01

The extraordinary capacity of phytate (myo-inositol hexaphosphate), a substance present in blood, urine, interstitial and intracellular fluids, to inhibit crystallization of calcium salts (oxalate and phosphate) is discussed. Its role in preventing calcium renal stone formation is specifically presented and discussed. "In vitro" and "in vivo" experiments, as well as clinical studies clearly demonstrated that phytate plays an important role as a crystallization inhibitor of calcium salts in biological fluids and becomes a clear alternative in the treatment of calcium oxalate renal lithiasis.

Characterization of the Chicken Ovarian Cancer Model

DTIC Science & Technology

2004-08-01

epithelium and usually contain eosinophilic proteinaceous fluid in their lumen. They have variable amounts of interstitial fibrovascular tissue and/or...alterations in oviductal glandular epithelium from normal to neoplastic (focal or multifocal hyperplasia -4 dysplasia -- adenoma [usually polypoid] -4

Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain.

PubMed

Iliff, Jeffrey J; Wang, Minghuan; Zeppenfeld, Douglas M; Venkataraman, Arun; Plog, Benjamin A; Liao, Yonghong; Deane, Rashid; Nedergaard, Maiken

2013-11-13

CSF from the subarachnoid space moves rapidly into the brain along paravascular routes surrounding penetrating cerebral arteries, exchanging with brain interstitial fluid (ISF) and facilitating the clearance of interstitial solutes, such as amyloid β, in a pathway that we have termed the "glymphatic" system. Prior reports have suggested that paravascular bulk flow of CSF or ISF may be driven by arterial pulsation. However, cerebral arterial pulsation could not be directly assessed. In the present study, we use in vivo two-photon microscopy in mice to visualize vascular wall pulsatility in penetrating intracortical arteries. We observed that unilateral ligation of the internal carotid artery significantly reduced arterial pulsatility by ~50%, while systemic administration of the adrenergic agonist dobutamine increased pulsatility of penetrating arteries by ~60%. When paravascular CSF-ISF exchange was evaluated in real time using in vivo two-photon and ex vivo fluorescence imaging, we observed that internal carotid artery ligation slowed the rate of paravascular CSF-ISF exchange, while dobutamine increased the rate of paravascular CSF-ISF exchange. These findings demonstrate that cerebral arterial pulsatility is a key driver of paravascular CSF influx into and through the brain parenchyma, and suggest that changes in arterial pulsatility may contribute to accumulation and deposition of toxic solutes, including amyloid β, in the aging brain.

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey

PubMed Central

Tanriverdi, Hakan; Erboy, Fatma; Altinsoy, Bulent; Uygur, Firat; Arasli, Mehmet; Ozel Tekin, Ishak; Tor, Muge Meltem; Atalay, Figen

2015-01-01

Background: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs. Objectives: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort. Patients and Methods: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups. Results: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16+56+, CD103+, CD8+103+, and CD3+16+56+ cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs. Conclusions: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs. PMID:26566455

Pericardial fluid level of heart-type cytoplasmic fatty acid-binding protein (H-FABP) is an indicator of severe myocardial ischemia.

PubMed

Tambara, Keiichi; Fujita, Masatoshi; Miyamoto, Shoichi; Doi, Kazuhiko; Nishimura, Kazunobu; Komeda, Masashi

2004-02-01

Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been reported as a sensitive and specific marker for the early diagnosis of acute myocardial infarction. Our hypothesis was that serum or pericardial fluid levels of H-FABP can reflect not only myocardial infarction but also myocardial ischemia. A total of 34 patients with unstable angina, who had anginal symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were classified into group A (n=17), and those without these symptoms and changes into group B (n=17). Blood and pericardial fluid samples were obtained immediately after median sternotomy, and serum and pericardial fluid levels of creatine kinase-MB, cardiac troponin-T, and H-FABP were measured. Serum H-FABP levels were slightly elevated compared with their normal values in both groups. While they showed no difference between groups A and B (group A vs. B: 8.5+/-1.0 vs. 7.1+/-0.7 ng/ml, P=0.25), pericardial fluid levels of H-FABP were significantly higher in group A than in group B (16.3+/-2.0 vs. 9.6+/-1.0 ng/ml, P=0.0046). H-FABP showed a weak correlation between its serum levels and pericardial fluid levels (r=0.40). Pericardial fluid levels of H-FABP reflect myocardial ischemia occurring within 24 h of their measurements. H-FABP may be secreted into the interstitial space by increased permeability of the myocardial cell membrane associated with severe myocardial ischemia. Thus, pericardial fluid reflects pathophysiological conditions of cardiomyocytes more sensitively than circulating blood.

Pulsatile Fluid Shear in Bone Remodeling

NASA Technical Reports Server (NTRS)

Frangos, John A.

1997-01-01

The objective of this investigation was to elucidate the sensitivity to transients in fluid shear stress in bone remodeling. Bone remodeling is clearly a function of the local mechanical environment which includes interstitial fluid flow. Traditionally, load-induced remodeling has been associated with low frequency (1-2 Hz) signals attributed to normal locomotion. McLeod and Rubin, however, demonstrated in vivo remodeling events associated with high frequency (15-30 Hz) loading. Likewise, other in vivo studies demonstrated that slowly applied strains did not trigger remodeling events. We therefore hypothesized that the mechanosensitive pathways which control bone maintenance and remodeling are differentially sensitive to varying rates of applied fluid shear stress.

Fluid-Driven Deformation of a Soft Granular Material

NASA Astrophysics Data System (ADS)

MacMinn, Christopher W.; Dufresne, Eric R.; Wettlaufer, John S.

2015-01-01

Compressing a porous, fluid-filled material drives the interstitial fluid out of the pore space, as when squeezing water out of a kitchen sponge. Inversely, injecting fluid into a porous material can deform the solid structure, as when fracturing a shale for natural gas recovery. These poromechanical interactions play an important role in geological and biological systems across a wide range of scales, from the propagation of magma through Earth's mantle to the transport of fluid through living cells and tissues. The theory of poroelasticity has been largely successful in modeling poromechanical behavior in relatively simple systems, but this continuum theory is fundamentally limited by our understanding of the pore-scale interactions between the fluid and the solid, and these problems are notoriously difficult to study in a laboratory setting. Here, we present a high-resolution measurement of injection-driven poromechanical deformation in a system with granular microsctructure: We inject fluid into a dense, confined monolayer of soft particles and use particle tracking to reveal the dynamics of the multiscale deformation field. We find that a continuum model based on poroelasticity theory captures certain macroscopic features of the deformation, but the particle-scale deformation field exhibits dramatic departures from smooth, continuum behavior. We observe particle-scale rearrangement and hysteresis, as well as petal-like mesoscale structures that are connected to material failure through spiral shear banding.

Pulse wave myelopathy: An update of an hypothesis highlighting the similarities between syringomyelia and normal pressure hydrocephalus.

PubMed

Bateman, Grant A

2015-12-01

Most hypotheses trying to explain the pathophysiology of idiopathic syringomyelia involve mechanisms whereby CSF is pumped against a pressure gradient, from the subarachnoid space into the cord parenchyma. On review, these theories have universally failed to explain the disease process. A few papers have suggested that the syrinx fluid may originate from the cord capillary bed itself. However, in these papers, the fluid is said to accumulate due to impaired fluid drainage out of the cord. Again, there is little evidence to substantiate this. This proffered hypothesis looks at the problem from the perspective that syringomyelia and normal pressure hydrocephalus are almost identical in their manifestations but only differ in their site of effect within the neuraxis. It is suggested that the primary trigger for syringomyelia is a reduction in the compliance of the veins draining the spinal cord. This reduces the efficiency of the pulse wave dampening, occurring within the cord parenchyma, increasing arteriolar and capillary pulse pressure. The increased capillary pulse pressure opens the blood-spinal cord barrier due to a direct effect upon the wall integrity and interstitial fluid accumulates due to an increased secretion rate. An increase in arteriolar pulse pressure increases the kinetic energy within the cord parenchyma and this disrupts the cytoarchitecture allowing the fluid to accumulate into small cystic regions in the cord. With time the cystic regions coalesce to form one large cavity which continues to increase in size due to the ongoing interstitial fluid secretion and the hyperdynamic cord vasculature. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Sliding enhances fluid and solute transport into buried articular cartilage contacts.

PubMed

Graham, B T; Moore, A C; Burris, D L; Price, C

2017-12-01

Solutes and interstitial water are naturally transported from cartilage by load-induced interstitial fluid pressures. Fluid and solute recovery during joint articulation have been primarily attributed to passive diffusion and mechanical 'pumping' from dynamic loading. This paper tests if the sliding action of articulation is a significant and independent driver of fluid and solute transport in cartilage. The large osteochondral samples utilized in the present study preserve the convergent wedges necessary for physiological hydrodynamics. Following static load-induced fluid exudation and prior to sliding, a fluorescent solute (AlexaFluor 633) was added to the lubricant bath. In situ confocal microscopy was used to quantify the transport of solute from the bath into the buried stationary contact area (SCA) during sliding. Following static exudation, significant reductions in friction and strain during sliding at 60 mm/s were accompanied by significant solute transport into the inaccessible center of the buried contact; no such transport was detected for the 0- or 1 mm/s sliding conditions. The results suggest that external hydrodynamic pressures from sliding induced advective flows that carried solutes from the bath toward the center of contact. These results provide the first direct evidence that the action of sliding is a significant contributor to fluid and solute recovery by cartilage. Furthermore, they indicate that the sliding-induced transport of solutes into the buried interface was orders of magnitude greater than that attributable to diffusion alone, a result with critical implications for disease prevention and tissue engineering. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Fluid flow and convective transport of solutes within the intervertebral disc.

PubMed

Ferguson, Stephen J; Ito, Keita; Nolte, Lutz P

2004-02-01

Previous experimental and analytical studies of solute transport in the intervertebral disc have demonstrated that for small molecules diffusive transport alone fulfils the nutritional needs of disc cells. It has been often suggested that fluid flow into and within the disc may enhance the transport of larger molecules. The goal of the study was to predict the influence of load-induced interstitial fluid flow on mass transport in the intervertebral disc. An iterative procedure was used to predict the convective transport of physiologically relevant molecules within the disc. An axisymmetric, poroelastic finite-element structural model of the disc was developed. The diurnal loading was divided into discrete time steps. At each time step, the fluid flow within the disc due to compression or swelling was calculated. A sequentially coupled diffusion/convection model was then employed to calculate solute transport, with a constant concentration of solute being provided at the vascularised endplates and outer annulus. Loading was simulated for a complete diurnal cycle, and the relative convective and diffusive transport was compared for solutes with molecular weights ranging from 400 Da to 40 kDa. Consistent with previous studies, fluid flow did not enhance the transport of low-weight solutes. During swelling, interstitial fluid flow increased the unidirectional penetration of large solutes by approximately 100%. Due to the bi-directional temporal nature of disc loading, however, the net effect of convective transport over a full diurnal cycle was more limited (30% increase). Further study is required to determine the significance of large solutes and the timing of their delivery for disc physiology.

Can the use of methylprednisolone, vitamin C, or alpha-trinositol prevent cold-induced fluid extravasation during cardiopulmonary bypass in piglets?

PubMed

Farstad, M; Heltne, J K; Rynning, S E; Onarheim, H; Mongstad, A; Eliassen, F; Husby, P

2004-02-01

Hypothermic cardiopulmonary bypass is associated with capillary fluid leakage, resulting in edema and occasionally organ dysfunction. Systemic inflammatory activation is considered responsible. In some studies methylprednisolone has reduced the weight gain during cardiopulmonary bypass. Vitamin C and alpha-trinositol have been demonstrated to reduce the microvascular fluid and protein leakage in thermal injuries. We therefore tested these three agents for the reduction of cold-induced fluid extravasation during cardiopulmonary bypass. A total of 28 piglets were randomly assigned to four groups of 7 each: control group, high-dose vitamin C group, methylprednisolone group, and alpha-trinositol-group. After 1 hour of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass was initiated in all animals and continued to 90 minutes. The fluid level in the extracorporeal circuit reservoir was kept constant at the 400-mL level and used as a fluid gauge. Fluid needs, plasma volume, changes in colloid osmotic pressure in plasma and interstitial fluid, hematocrit, and total water contents in different tissues were recorded, and the protein masses and the fluid extravasation rate were calculated. Hemodilution was about 25% after start of normothermic cardiopulmonary bypass. Cooling did not cause any further changes in hemodilution. During steady-state normothermic cardiopulmonary bypass, the fluid need in all groups was about 0.10 mL/(kg.min), with a 9-fold increase during the first 30 minutes of cooling (P <.001). This increased fluid need was due mainly to increased fluid extravasation from the intravascular to the interstitial space at a mean rate of 0.6 mL/(kg.min) (range 0.5-0.7 mL/[kg.min]; P <.01) and was reflected by increased total water content in most tissues in all groups. The albumin and protein masses remained constant in all groups throughout the study. Pretreatment with methylprednisolone, vitamin C, or alpha-trinositol was unable to prevent the increased fluid extravasation rate during hypothermic cardiopulmonary bypass. These findings, together with the stability of the protein masses throughout the study, support the presence of a noninflammatory mechanism behind the cold-induced fluid leakage seen during cardiopulmonary bypass.

Effect of α-trinositol on interstitial fluid pressure, oedema generation and albumin extravasation in experimental frostbite in the rat

PubMed Central

Berg, A; Aas, P; Gustafsson, T; Reed, R K

1999-01-01

The anti-inflammatory effect of α-trinositol (D-myo-inositol-1,2,6-trisphosphate) on oedema formation, microvascular protein leakage and interstitial fluid pressure (Pif) in rat skin after frostbite injury, was investigated. α-Trinositol (40 mg kg body weight−1) was administered intravenously as a bolus both before and/or in the interval between freezing and thawing of the tissue. Pif was measured in rat paw skin with micropipettes connected to a servo-controlled counterpressure system. Oedema formation was estimated by measuring the increase in total tissue water content (wet weight minus dry weight divided by dry weight). Albumin extravasation (i.e., the difference between the plasma equivalent space for 125I- and 131I-human serum albumin (HSA) circulating for different time intervals) was used to estimate the microvascular leakage. Compared to untreated animals, α-trinositol given pre- and/or post-freeze reduced total tissue water and albumin extravasation as well as the fall in Pif in injured tissue significantly (P<0.05). α-Trinositol given only post-freeze reduced total tissue water and albumin extravasation from 4.46±0.93 and 2.37±1.12 to 2.51±0.29 and 0.36±0.18 ml g dry weight−1, respectively (P<0.05). Pif fell from −0.8±0.2 mmHg pre-freeze to −3.4±1.0 mmHg (P<0.05) at 20 min after tissue injury (circulatory arrest) and was attenuated by treatment with α-trinositol. We conclude that α-trinositol exerts its anti-oedematous effect by acting on the extracellular matrix, attenuating the lowering of Pif as well as on the microvascular wall, thereby decreasing the protein extravasation. PMID:10217530

Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways

PubMed Central

Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, DL; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

2015-01-01

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm2) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified. PMID:25435370

Fluid shear promotes chondrosarcoma cell invasion by activating matrix metalloproteinase 12 via IGF-2 and VEGF signaling pathways.

PubMed

Wang, P; Chen, S-H; Hung, W-C; Paul, C; Zhu, F; Guan, P-P; Huso, D L; Kontrogianni-Konstantopoulos, A; Konstantopoulos, K

2015-08-27

Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified.

Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow.

PubMed

Holter, Karl Erik; Kehlet, Benjamin; Devor, Anna; Sejnowski, Terrence J; Dale, Anders M; Omholt, Stig W; Ottersen, Ole Petter; Nagelhus, Erlend Arnulf; Mardal, Kent-André; Pettersen, Klas H

2017-09-12

The brain lacks lymph vessels and must rely on other mechanisms for clearance of waste products, including amyloid [Formula: see text] that may form pathological aggregates if not effectively cleared. It has been proposed that flow of interstitial fluid through the brain's interstitial space provides a mechanism for waste clearance. Here we compute the permeability and simulate pressure-mediated bulk flow through 3D electron microscope (EM) reconstructions of interstitial space. The space was divided into sheets (i.e., space between two parallel membranes) and tunnels (where three or more membranes meet). Simulation results indicate that even for larger extracellular volume fractions than what is reported for sleep and for geometries with a high tunnel volume fraction, the permeability was too low to allow for any substantial bulk flow at physiological hydrostatic pressure gradients. For two different geometries with the same extracellular volume fraction the geometry with the most tunnel volume had [Formula: see text] higher permeability, but the bulk flow was still insignificant. These simulation results suggest that even large molecule solutes would be more easily cleared from the brain interstitium by diffusion than by bulk flow. Thus, diffusion within the interstitial space combined with advection along vessels is likely to substitute for the lymphatic drainage system in other organs.

Viscous Dynamics of Lyme Disease and Syphilis Spirochetes Reveal Flagellar Torque and Drag

PubMed Central

Harman, Michael; Vig, Dhruv K.; Radolf, Justin D.; Wolgemuth, Charles W.

2013-01-01

The spirochetes that cause Lyme disease (Borrelia burgdorferi) and syphilis (Treponema pallidum) swim through viscous fluids, such as blood and interstitial fluid, by undulating their bodies as traveling, planar waves. These undulations are driven by rotation of the flagella within the periplasmic space, the narrow (∼20–40 nm in width) compartment between the inner and outer membranes. We show here that the swimming speeds of B. burgdorferi and T. pallidum decrease with increases in viscosity of the external aqueous milieu, even though the flagella are entirely intracellular. We then use mathematical modeling to show that the measured changes in speed are consistent with the exertion of constant torque by the spirochetal flagellar motors. Comparison of simulations, experiments, and a simple model for power dissipation allows us to estimate the torque and resistive drag that act on the flagella of these major spirochetal pathogens. PMID:24268139

Dicarbonyl stress in clinical obesity.

PubMed

Masania, Jinit; Malczewska-Malec, Malgorzata; Razny, Urszula; Goralska, Joanna; Zdzienicka, Anna; Kiec-Wilk, Beata; Gruca, Anna; Stancel-Mozwillo, Julita; Dembinska-Kiec, Aldona; Rabbani, Naila; Thornalley, Paul J

2016-08-01

The glyoxalase system in the cytoplasm of cells provides the primary defence against glycation by methylglyoxal catalysing its metabolism to D-lactate. Methylglyoxal is the precursor of the major quantitative advanced glycation endproducts in physiological systems - arginine-derived hydroimidazolones and deoxyguanosine-derived imidazopurinones. Glyoxalase 1 of the glyoxalase system was linked to anthropometric measurements of obesity in human subjects and to body weight in strains of mice. Recent conference reports described increased weight gain on high fat diet-fed mouse with lifelong deficiency of glyoxalase 1 deficiency, compared to wild-type controls, and decreased weight gain in glyoxalase 1-overexpressing transgenic mice, suggesting a functional role of glyoxalase 1 and dicarbonyl stress in obesity. Increased methylglyoxal, dicarbonyl stress, in white adipose tissue and liver may be a mediator of obesity and insulin resistance and thereby a risk factor for development of type 2 diabetes and non-alcoholic fatty liver disease. Increased methylglyoxal formation from glyceroneogenesis on adipose tissue and liver and decreased glyoxalase 1 activity in obesity likely drives dicarbonyl stress in white adipose tissue increasing the dicarbonyl proteome and related dysfunction. The clinical significance will likely emerge from on-going clinical evaluation of inducers of glyoxalase 1 expression in overweight and obese subjects. Increased transcapillary escape rate of albumin and increased total body interstitial fluid volume in obesity likely makes levels of glycation of plasma protein unreliable indicators of glycation status in obesity as there is a shift of albumin dwell time from plasma to interstitial fluid, which decreases overall glycation for a given glycemic exposure.

Subharmonic-Aided Pressure Estimation for Monitoring Interstitial Fluid Pressure in Tumors: Calibration and Treatment with Paclitaxel in Breast Cancer Xenografts.

PubMed

Halldorsdottir, Valgerdur G; Dave, Jaydev K; Marshall, Andrew; Forsberg, Anya I; Fox, Traci B; Eisenbrey, John R; Machado, Priscilla; Liu, Ji-Bin; Merton, Daniel A; Forsberg, Flemming

2017-07-01

Interstitial fluid pressure (IFP) in rats with breast cancer xenografts was non-invasively estimated using subharmonic-aided pressure estimation (SHAPE) versus an invasive pressure monitor. Moreover, monitoring of IFP changes after chemotherapy was assessed. Eighty-nine rats (calibration n = 25, treatment n = 64) were injected with 5 × 10 6 breast cancer cells (MDA-MB-231). Radiofrequency signals were acquired (39 rats successfully imaged) with a Sonix RP scanner (BK Ultrasound, Richmond, BC, Canada) using a linear array (L9-4, transmit/receive: 8/4 MHz) after administration of Definity (Lantheus Medical Imaging, North Billerica, MA, USA; 180 μL/kg) and compared with readings from an invasive pressure monitor (Stryker, Berkshire, UK). An inverse linear relationship was established between tumor IFP and SHAPE (y = -1.06x + 28.27, r = -0.69, p = 0.01) in the calibration group. Use of this relationship in the treatment group resulted in r = 0.74 (p < 0.05) between measured (pressure monitor) and SHAPE-estimated IFP (average error: 6.24 mmHg). No significant before/after differences were observed with respect to paclitaxel treatment (5 mg/kg, Mayne Pharma, Paramus, NJ, USA) with either method (p ≥ 0.15). Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone.

PubMed

Milosevic, Michael F; Pintilie, Melania; Hedley, David W; Bristow, Robert G; Wouters, Bradly G; Oza, Amit M; Laframboise, Stephane; Hill, Richard P; Fyles, Anthony W

2014-10-01

Radiotherapy (RT) with concurrent cisplatin (CRT) is standard treatment for locally advanced cervical cancer. However, not all patients benefit from the addition of cisplatin to RT alone. This study explored the value of pretreatment tumor interstitial fluid pressure (IFP) and hypoxia measurements as predictors of cisplatin response in 291 patients who were treated with RT (1994-1998) or RT plus concurrent cisplatin (1999-2009). Clinical characteristics were similar between the two groups, apart from a greater proportion of patients with pelvic lymph node metastases and hypoxic tumors in the CRT cohort. Patients were followed for a median duration of 5.6 years. Information about recurrence and survival was recorded prospectively. The addition of cisplatin to RT improved survival compared to treatment with RT alone (HR 0.61, p = 0.0097). This improvement was confined to patients with high-IFP tumors at diagnosis (HR 0.40, p = 0.00091). There was no benefit of adding cisplatin in those with low-IFP tumors (HR 1.05, p = 0.87). There was no difference in the effectiveness of cisplatin in patients with more or less hypoxic tumors. In conclusion, patients with locally advanced cervical cancer and high tumor IFP at diagnosis have greater benefit from the addition of cisplatin to RT than those with low IFP. This may reflect high tumor cell proliferation, which is known to influence IFP, local tumor control and patient survival. © 2013 UICC.

Modeling of Soft Poroelastic Tissue in Time-Harmonic MR Elastography

PubMed Central

Perriñez, Phillip R.; Kennedy, Francis E.; Van Houten, Elijah E. W.; Weaver, John B.; Paulsen, Keith D.

2010-01-01

Elastography is an emerging imaging technique that focuses on assessing the resistance to deformation of soft biological tissues in vivo. Magnetic resonance elastography (MRE) uses measured displacement fields resulting from low-amplitude, low-frequency (10 Hz–1 kHz) time-harmonic vibration to recover images of the elastic property distribution of tissues including breast, liver, muscle, prostate, and brain. While many soft tissues display complex time-dependent behavior not described by linear elasticity, the models most commonly employed in MRE parameter reconstructions are based on elastic assumptions. Further, elasticity models fail to include the interstitial fluid phase present in vivo. Alternative continuum models, such as consolidation theory, are able to represent tissue and other materials comprising two distinct phases, generally consisting of a porous elastic solid and penetrating fluid. MRE reconstructions of simulated elastic and poroelastic phantoms were performed to investigate the limitations of current-elasticity-based methods in producing accurate elastic parameter estimates in poroelastic media. The results indicate that linearly elastic reconstructions of fluid-saturated porous media at amplitudes and frequencies relevant to steady-state MRE can yield misleading effective property distributions resulting from the complex interaction between their solid and fluid phases. PMID:19272864

Electrostatic, elastic and hydration-dependent interactions in dermis influencing volume exclusion and macromolecular transport.

PubMed

Øien, Alf H; Wiig, Helge

2016-07-07

Interstitial exclusion refers to the limitation of space available for plasma proteins and other macromolecules based on collagen and negatively charged glycosaminoglycans (GAGs) in the interstitial space. It is of particular importance to interstitial fluid and plasma volume regulation. Here we present a novel mechanical and mathematical model of the dynamic interactions of structural elements within the interstitium of the dermis at the microscopic level that may explain volume exclusion of charged and neutral macroparticles. At this level, the interstitium is considered to consist of elements called extracellular matrix (ECM) cells, again containing two main interacting structural components on a fluid background including anions and cations setting up osmotic forces: one smaller GAG component, having an intrinsic expansive electric force, and one bigger collagen component, having an intrinsic elastic force. Because of size differences, the GAG component interacts with a fraction of the collagen component only at normal hydration. This fraction, however, increases with rising hydration as a consequence of the modeled form of the interaction force between the GAGs and collagen. Collagen is locally displaced at variable degrees as hydration changes. Two models of GAGs are considered, having largely different geometries which demands different, but related, forms of GAG-collagen interaction forces. The effects of variable fixed charges on GAGs and of GAG density in tissue are evaluated taking into account observed volume exclusion properties of charged macromolecules as a function of tissue hydration. The presented models may improve our biophysical understanding of acting forces influencing tissue fluid dynamics. Such knowledge is significant when evaluating the transport of electrically charged and neutral macromolecules into and through the interstitium, and therefore to drug uptake and the therapeutic effects of macromolecular agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyaluronan Production by Renomedullary Interstitial Cells: Influence of Endothelin, Angiotensin II and Vasopressin

PubMed Central

Palm, Fredrik; Takahashi, Tomoko; Ikegami-Kawai, Mayumi; Friederich-Persson, Malou; Hansell, Peter

2017-01-01

The content of hyaluronan (HA) in the interstitium of the renal medulla changes in relation to body hydration status. We investigated if hormones of central importance for body fluid homeostasis affect HA production by renomedullary interstitial cells in culture (RMICs). Simultaneous treatment with vasopressin and angiotensin II (Ang II) reduced HA by 69%. No change occurred in the mRNA expressions of hyaluronan synthase 2 (HAS2) or hyaluronidases (Hyals), while Hyal activity in the supernatant increased by 67% and CD44 expression reduced by 42%. The autocoid endothelin (ET-1) at low concentrations (10−10 and 10−8 M) increased HA 3-fold. On the contrary, at a high concentration (10−6 M) ET-1 reduced HA by 47%. The ET-A receptor antagonist BQ123 not only reversed the reducing effect of high ET-1 on HA, but elevated it to the same level as low concentration ET-1, suggesting separate regulating roles for ET-A and ET-B receptors. This was corroborated by the addition of ET-B receptor antagonist BQ788 to low concentration ET-1, which abolished the HA increase. HAS2 and Hyal2 mRNA did not alter, while Hyal1 mRNA was increased at all ET-1 concentrations tested. Hyal activity was elevated the most by high ET-1 concentration, and blockade of ET-A receptors by BQ123 prevented about 30% of this response. The present study demonstrates an important regulatory influence of hormones involved in body fluid balance on HA handling by RMICs, thereby supporting the concept of a dynamic involvement of interstitial HA in renal fluid handling. PMID:29236055

Glucose predictability, blood capillary permeability, and glucose utilization rate in subcutaneous, skeletal muscle, and visceral fat tissues.

PubMed

Koutny, Tomas

2013-11-01

This study suggests an approach for the comparison and evaluation of particular compartments with modest experimental setup costs. A glucose level prediction model was used to evaluate the compartment's glucose transport rate across the blood capillary membrane and the glucose utilization rate by the cells. The glucose levels of the blood, subcutaneous tissue, skeletal muscle tissue, and visceral fat were obtained in experiments conducted on hereditary hypertriglyceridemic rats. After the blood glucose level had undergone a rapid change, the experimenter attempted to reach a steady blood glucose level by manually correcting the glucose infusion rate and maintaining a constant insulin infusion rate. The interstitial fluid glucose levels of subcutaneous tissue, skeletal muscle tissue, and visceral fat were evaluated to determine the reaction delay compared with the change in the blood glucose level, the interstitial fluid glucose level predictability, the blood capillary permeability, the effect of the concentration gradient, and the glucose utilization rate. Based on these data, the glucose transport rate across the capillary membrane and the utilization rate in a particular tissue were determined. The rates obtained were successfully verified against positron emission tomography experiments. The subcutaneous tissue exhibits the lowest and the most predictable glucose utilization rate, whereas the skeletal muscle tissue has the greatest glucose utilization rate. In contrast, the visceral fat is the least predictable and has the shortest reaction delay compared with the change in the blood glucose level. The reaction delays obtained for the subcutaneous tissue and skeletal muscle tissue were found to be approximately equal using a metric based on the time required to reach half of the increase in the interstitial fluid glucose level. © 2013 Published by Elsevier Ltd.

A new airborne sampler for interstitial particles in ice and liquid clouds

NASA Astrophysics Data System (ADS)

Moharreri, A.; Craig, L.; Rogers, D. C.; Brown, M.; Dhaniyala, S.

2011-12-01

In-situ measurements of cloud droplets and aerosols using aircraft platforms are required for understanding aerosol-cloud processes and aiding development of improved aerosol-cloud models. A variety of clouds with different temperature ranges and cloud particle sizes/phases must be studied for comprehensive knowledge about the role of aerosols in the formation and evolution of cloud systems under different atmospheric conditions. While representative aerosol measurements are regularly made from aircrafts under clear air conditions, aerosol measurements in clouds are often contaminated by the generation of secondary particles from the high speed impaction of ice particles and liquid droplets on the surfaces of the aircraft probes/inlets. A new interstitial particle sampler, called the blunt-body aerosol sampler (BASE) has been designed and used for aerosol sampling during two recent airborne campaigns using NCAR/NSF C-130 aircraft: PLOWS (2009-2010) and ICE-T (2011). Central to the design of the new interstitial inlet is an upstream blunt body housing that acts to shield/deflect large cloud droplets and ice particles from an aft sampling region. The blunt-body design also ensures that small shatter particles created from the impaction of cloud-droplets on the blunt-body are not present in the aft region where the interstitial inlet is located. Computational fluid dynamics (CFD) simulations along with particle transport modeling and wind tunnel studies have been utilized in different stages of design and development of this inlet. The initial flights tests during the PLOWS campaign showed that the inlet had satisfactory performance only in warm clouds and when large precipitation droplets were absent. In the presence of large droplets and ice, the inlet samples were contaminated with significant shatter artifacts. These initial results were reanalyzed in conjunction with a computational droplet shatter model and the numerical results were used to arrive at an improved sampler design. Analysis of the data from the recent ICE-T campaign with the improved sampler design shows that the modified version of BASE can provide shatter-artifact free sampling of aerosol particles in the presence of ice particles and significantly reduced shatter artifacts in warm clouds. Detailed design and modeling aspects of the sampler will be discussed and the sampler performance in warm and cold clouds will be presented and compared with measurements made using other aerosol inlets flown on the NCAR/NSF C-130 aircraft.

Towards the Early Detection of Breast Cancer in Young Women

DTIC Science & Technology

2006-10-01

approach. 4. Poroelastic model for tissue deformation: We have implemented the model of Netti et al. in a finite element program in order to simulate...changes would not be expected. 44Interstitial Fluid Flow 5. Conclusions A poroelastic model that includes the effects of fluid flow and the possibility of...images to produce a displacement field. Using this displacement field, and an assumed linear elastic model for the tissue, an inverse problem is solved

Influence of interstitial Mn on magnetism in the room-temperature ferromagnet Mn 1 + δ Sb

DOE PAGES

Taylor, Alice E.; Berlijn, Tom; Hahn, Steven E.; ...

2015-06-15

We repormore » t elastic and inelastic neutron scattering measurements of the high-TC ferromagnet Mn 1 + δ Sb . Measurements were performed on a large, T C = 434 K, single crystal with interstitial Mn content of δ ≈ 0.13. The neutron diffraction results reveal that the interstitial Mn has a magnetic moment, and that it is aligned antiparallel to the main Mn moment. We perform density functional theory calculations including the interstitial Mn, and find the interstitial to be magnetic in agreement with the diffraction data. The inelastic neutron scattering measurements reveal two features in the magnetic dynamics: i) a spin-wave-like dispersion emanating from ferromagnetic Bragg positions (H K 2n), and ii) a broad, non-dispersive signal centered at forbidden Bragg positions (H K 2n+1). The inelastic spectrum cannot be modeled by simple linear spin-wave theory calculations, and appears to be significantly altered by the presence of the interstitial Mn ions. Finally, the results show that the influence of the interstitial Mn on the magnetic state in this system is more important than previously understood.« less

Local pressure and matrix component effects on verteporfin distribution in pancreatic tumors (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nieskoski, Michael D.; Marra, Kayla; Gunn, Jason R.; Doyley, Marvin; Samkoe, Kimberly S.; Pereira, Stephen P.; Trembly, B. Stuart; Pogue, Brian W.

2017-02-01

Pancreatic tumors are characterized by large interstitial hypertension from enhanced deposition of extracellular matrix components, resulting in widespread vascular collapse and reduced molecular uptake of systemically delivered therapies. Although the origins of hypoperfusion is debated amongst researchers, spatial distribution of collagen density and hyaluronic acid content have shown to be a key metric in understanding the lack of efficacy for both acute and chronic therapies in these tumors. In this study, the AsPC-1 tumor model was used both subcutaneously and orthotopically to study the measurable factors which are related to this. A conventional piezoelectric pressure catheter was used to measure total tissue pressure (TTP), defined as a combination of solid stress (SS) and interstitial fluid pressure (IFP), TTP = SS + IFP, in multiple locations within the tumor interstitium. Matrix components such as collagen and hyaluronic acid were scored using masson's trichrome stain and hyaluronic acid binding protein (HABP), respectively, and co-registered with values of TTP. The results show that these key measurements are related to the spatial distribution of verteporfin in the same tumors. Photodynamic treatment with verteporfin is known to ablate large regions of tumor tissue and also allow better permeability for chemotherapies. The study of spatial distribution of verteporfin in relation to stromal content and TTP will help us better control these types of combination therapies.

Dynamic interaction between myocardial contraction and coronary flow.

PubMed

Beyar, R; Sideman, S

1997-01-01

Phasic coronary flow is determined by the dynamic interaction between central hemodynamics and myocardial and ventricular mechanics. Various models, including the waterfall, intramyocardial pump and myocardial structural models, have been proposed for the coronary circulation. Concepts such as intramyocardial pressure, local elastance and others have been proposed to help explain the coronary compression by the myocardium. Yet some questions remain unresolved, and a new model has recently been proposed, linking a muscle collagen fibrous model to a physiologically based coronary model, and accounting for transport of fluids across the capillaries and lymphatic flow between the interstitial space and the venous system. One of the unique features of this model is that the intramyocardial pressure (IMP) in the interstitial space is calculated from the balance of forces and fluid transport in the system, and is therefore dependent on the coronary pressure conditions, the myocardial function and the transport properties of the system. The model predicts a wide range of experimentally observed phenomena associated with coronary compression.

A near infrared holographic glucose sensor.

PubMed

Vezouviou, Evangelia; Lowe, Christopher R

2015-06-15

Real-time glucose monitoring has been beneficial in reducing health complications associated with diabetes as well as a decrease in mortality. This report describes a novel holographic platform, fabricated via laser ablation on chitosan hydrogel with gold nanoparticles with a replaying in visible and near IR. The sensor responded with a 12 nm and 7 nm shift in wavelength at glucose concentrations in the 0-70 mM range and in the visible and near IR, respectively, at pH 7.4 and an ionic strength of 154 mM. The sensor did not respond to potential interferences found in the interstitial fluid, such as fructose, vitamin C and lactate, at their respective normal concentrations and was stable to fluctuations in temperature, pH and ionic strength. The characteristics of this sensor suggests that it may be applicable for use as an implanted device for the real time monitoring of glucose concentrations in the interstitial fluid using near IR as the interrogating medium. Copyright © 2015 Elsevier B.V. All rights reserved.

Diffusion and interactions of interstitials in hard-sphere interstitial solid solutions

NASA Astrophysics Data System (ADS)

van der Meer, Berend; Lathouwers, Emma; Smallenburg, Frank; Filion, Laura

2017-12-01

Using computer simulations, we study the dynamics and interactions of interstitial particles in hard-sphere interstitial solid solutions. We calculate the free-energy barriers associated with their diffusion for a range of size ratios and densities. By applying classical transition state theory to these free-energy barriers, we predict the diffusion coefficients, which we find to be in good agreement with diffusion coefficients as measured using event-driven molecular dynamics simulations. These results highlight that transition state theory can capture the interstitial dynamics in the hard-sphere model system. Additionally, we quantify the interactions between the interstitials. We find that, apart from excluded volume interactions, the interstitial-interstitial interactions are almost ideal in our system. Lastly, we show that the interstitial diffusivity can be inferred from the large-particle fluctuations alone, thus providing an empirical relationship between the large-particle fluctuations and the interstitial diffusivity.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

2013 AAHA/AAFP fluid therapy guidelines for dogs and cats.

PubMed

Davis, Harold; Jensen, Tracey; Johnson, Anthony; Knowles, Pamela; Meyer, Robert; Rucinsky, Renee; Shafford, Heidi

2013-01-01

Fluid therapy is important for many medical conditions in veterinary patients. The assessment of patient history, chief complaint, physical exam findings, and indicated additional testing will determine the need for fluid therapy. Fluid selection is dictated by the patient's needs, including volume, rate, fluid composition required, and location the fluid is needed (e.g., interstitial versus intravascular). Therapy must be individualized, tailored to each patient, and constantly re-evaluated and reformulated according to changes in status. Needs may vary according to the existence of either acute or chronic conditions, patient pathology (e.g., acid-base, oncotic, electrolyte abnormalities), and comorbid conditions. All patients should be assessed for three types of fluid disturbances: changes in volume, changes in content, and/or changes in distribution. The goals of these guidelines are to assist the clinician in prioritizing goals, selecting appropriate fluids and rates of administration, and assessing patient response to therapy. These guidelines provide recommendations for fluid administration for anesthetized patients and patients with fluid disturbances.

Role of hyaluronan chain length in buffering interstitial flow across synovium in rabbits

PubMed Central

Coleman, P J; Scott, D; Mason, R M; Levick, J R

2000-01-01

Synovial fluid drains out of joints through an interstitial pathway. Hyaluronan, the major polysaccharide of synovial fluid, attenuates this fluid drainage; it creates a graded opposition to outflow that increases with pressure (outflow ‘buffering’). This has been attributed to size-related molecular reflection at the interstitium-fluid interface. Chain length is reduced in inflammatory arthritis. We therefore investigated the dependence of outflow buffering on hyaluronan chain length.Hyaluronan molecules of mean molecular mass ≈2200, 530, 300 and 90 kDa and concentration 3.6 mg ml−1 were infused into the knees of anaesthetized rabbits, with Ringer solution as control in the contralateral joint. Trans-synovial drainage rate was recorded at known joint pressures. Pressure was raised in steps every 30–60 min (range 2–24 cmH2O).With hyaluronan-90 and hyaluronan-300 the fluid drainage rate was reduced relative to Ringer solution (P < 0.001, ANOVA) but increased steeply with pressure. The opposition to outflow, defined as the pressure required to drive unit outflow, did not increase with pressure, i.e. there was no outflow buffering.With hyaluronan-530 and hyaluronan-2000 the fluid drainage rate became relatively insensitive to pressure, causing a near plateau of flow. Opposition to outflow increased markedly with pressure, by up to 3.3 times over the explored pressures.Hyaluronan concentration in the joint cavity increased over the drainage period, indicating partial reflection of hyaluronan by synovial interstitium. Reflected fractions were 0.12, 0.33, 0.25 and 0.79 for hyaluronan-90, -300, -530 and -2200, respectively.Thus the flow-buffering effect of hyaluronan depended on chain length, and shortening the chains reduced the degree of molecular reflection. The latter should reduce the concentration polarization at the tissue interface, and hence the local osmotic pressure opposing fluid drainage. In rheumatoid arthritis the reduced chain length will facilitate the escape of hyaluronan and fluid. PMID:10896731

Water immersion and its computer simulation as analogs of weightlessness

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1982-01-01

Experimental studies and computer simulations of water immersion are summarized and discussed with regard to their utility as analogs of weightlessness. Emphasis is placed on describing and interpreting the renal, endocrine, fluid, and circulatory changes that take place during immersion. A mathematical model, based on concepts of fluid volume regulation, is shown to be well suited to simulate the dynamic responses to water immersion. Further, it is shown that such a model provides a means to study specific mechanisms and pathways involved in the immersion response. A number of hypotheses are evaluated with the model related to the effects of dehydration, venous pressure disturbances, the control of ADH, and changes in plasma-interstitial volume. By inference, it is suggested that most of the model's responses to water immersion are plausible predictions of the acute changes expected, but not yet measured, during space flight. One important prediction of the model is that previous attempts to measure a diuresis during space flight failed because astronauts may have been dehydrated and urine samples were pooled over 24-hour periods.

Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma.

PubMed

DuFort, Christopher C; DelGiorno, Kathleen E; Hingorani, Sunil R

2016-06-01

The microenvironment influences the pathogenesis of solid tumors and plays an outsized role in some. Our understanding of the stromal response to cancers, particularly pancreatic ductal adenocarcinoma, has evolved from that of host defense to tumor offense. We know that most, although not all, of the factors and processes in the microenvironment support tumor epithelial cells. This reappraisal of the roles of stromal elements has also revealed potential vulnerabilities and therapeutic opportunities to exploit. The high concentration in the stroma of the glycosaminoglycan hyaluronan, together with the large gel-fluid phase and pressures it generates, were recently identified as primary sources of treatment resistance in pancreas cancer. Whereas the relatively minor role of free interstitial fluid in the fluid mechanics and perfusion of tumors has been long appreciated, the less mobile, gel-fluid phase has been largely ignored for historical and technical reasons. The inability of classic methods of fluid pressure measurement to capture the gel-fluid phase, together with a dependence on xenograft and allograft systems that inaccurately model tumor vascular biology, has led to an undue emphasis on the role of free fluid in impeding perfusion and drug delivery and an almost complete oversight of the predominant role of the gel-fluid phase. We propose that a hyaluronan-rich, relatively immobile gel-fluid phase induces vascular collapse and hypoperfusion as a primary mechanism of treatment resistance in pancreas cancers. Similar properties may be operant in other solid tumors as well, so revisiting and characterizing fluid mechanics with modern techniques in other autochthonous cancers may be warranted. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of hydration on steric and electric charge-induced interstitial volume exclusion--a model.

PubMed

Øien, Alf H; Justad, Sigrid R; Tenstad, Olav; Wiig, Helge

2013-09-03

The presence of collagen and charged macromolecules like glycosaminoglycans (GAGs) in the interstitial space limits the space available for plasma proteins and other macromolecules. This phenomenon, known as interstitial exclusion, is of importance for interstitial fluid volume regulation. Physical/mathematical models are presented for calculating the exclusion of electrically charged and neutral macromolecules that equilibrate in the interstitium under various degrees of hydration. Here, a central hypothesis is that the swelling of highly electrically charged GAGs with increased hydration shields parts of the neutral collagen of the interstitial matrix from interacting with electrically charged macromolecules, such that exclusion of charged macromolecules exhibits change due to steric and charge effects. GAGs are also thought to allow relatively small neutral, but also charged macromolecules neutralized by a very high ionic strength, diffuse into the interior of GAGs, whereas larger macromolecules may not. Thus, in the model, relatively small electrically charged macromolecules, such as human serum albumin, and larger neutral macromolecules such as IgG, will have quite similar total volume exclusion properties in the interstitium. Our results are in agreement with ex vivo and in vivo experiments, and suggest that the charge of GAGs or macromolecular drugs may be targeted to increase the tissue uptake of macromolecular therapeutic agents. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Barrier Coatings for Refractory Metals and Superalloys

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

SM Sabol; BT Randall; JD Edington

2006-02-23

In the closed working fluid loop of the proposed Prometheus space nuclear power plant (SNPP), there is the potential for reaction of core and plant structural materials with gas phase impurities and gas phase transport of interstitial elements between superalloy and refractory metal alloy components during service. Primary concerns are surface oxidation, interstitial embrittlement of refractory metals and decarburization of superalloys. In parallel with kinetic investigations, this letter evaluates the ability of potential coatings to prevent or impede communication between reactor and plant components. Key coating requirements are identified and current technology coating materials are reviewed relative to these requirements.more » Candidate coatings are identified for future evaluation based on current knowledge of design parameters and anticipated environment. Coatings were identified for superalloys and refractory metals to provide diffusion barriers to interstitial transport and act as reactive barriers to potential oxidation. Due to their high stability at low oxygen potential, alumina formers are most promising for oxidation protection given the anticipated coolant gas chemistry. A sublayer of iridium is recommended to provide inherent diffusion resistance to interstitials. Based on specific base metal selection, a thin film substrate--coating interdiffusion barrier layer may be necessary to meet mission life.« less

Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

PubMed

Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

2015-10-01

Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.

Novel Assessment of Interstitial Lung Disease Using the "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) Software System in Idiopathic Inflammatory Myopathies.

PubMed

Ungprasert, Patompong; Wilton, Katelynn M; Ernste, Floranne C; Kalra, Sanjay; Crowson, Cynthia S; Rajagopalan, Srinivasan; Bartholmai, Brian J

2017-10-01

To evaluate the correlation between measurements from quantitative thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) software and measurements from pulmonary function tests (PFTs) in patients with idiopathic inflammatory myopathies (IIM)-associated interstitial lung disease (ILD). A cohort of patients with IIM-associated ILD seen at Mayo Clinic was identified from medical record review. Retrospective analysis of HRCT data and PFTs at baseline and 1 year was performed. The abnormalities in HRCT were quantified using CALIPER software. A total of 110 patients were identified. At baseline, total interstitial abnormalities as measured by CALIPER, both by absolute volume and by percentage of total lung volume, had a significant negative correlation with diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and oxygen saturation. Analysis by subtype of interstitial abnormality revealed significant negative correlations between ground glass opacities (GGO) and reticular density (RD) with DLCO and TLC. At one year, changes of total interstitial abnormalities compared with baseline had a significant negative correlation with changes of TLC and oxygen saturation. A negative correlation between changes of total interstitial abnormalities and DLCO was also observed, but it was not statistically significant. Analysis by subtype of interstitial abnormality revealed negative correlations between changes of GGO and RD and changes of DLCO, TLC, and oxygen saturation, but most of the correlations did not achieve statistical significance. CALIPER measurements correlate well with functional measurements in patients with IIM-associated ILD.

Pharmacology of colloids and crystalloids.

PubMed

Griffel, M I; Kaufman, B S

1992-04-01

We have attempted to review body fluid distribution by compartments so that the reader understands the physiology of ICF and ECF, and the relationship between interstitial and intravascular fluids. Crystalloids such as NS and RL are distributed to the ECF, whereas colloids primarily remain intravascular for longer periods. Although effective, crystalloids tend to require larger volumes for infusion, and edema remains a problem. Colloids as a group are extremely effective volume expanders, but none is ideal. Albumin, hetastarch, dextran, and the less commonly used colloids each have significant toxicities that must be considered when using them. Intelligent choices can be made to optimize use of these fluids.

Diagnosis and management of dehydration in children.

PubMed

Canavan, Amy; Arant, Billy S

2009-10-01

The most useful individual signs for identifying dehydration in children are prolonged capillary refill time, abnormal skin turgor, and abnormal respiratory pattern. However, clinical dehydration scales based on a combination of physical examination findings are better predictors than individual signs. Oral rehydration therapy is the preferred treatment of mild to moderate dehydration caused by diarrhea in children. Appropriate oral rehydration therapy is as effective as intravenous fluid in managing fluid and electrolyte losses and has many advantages. Goals of oral rehydration therapy are restoration of circulating blood volume, restoration of interstitial fluid volume, and maintenance of rehydration. When rehydration is achieved, a normal age-appropriate diet should be initiated.

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy.

PubMed

Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

2017-01-01

The paravascular pathway, also known as the "glymphatic" pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.

The influence of size, clearance, cartilage properties, thickness and hemiarthroplasty on the contact mechanics of the hip joint with biphasic layers☆

PubMed Central

Li, Junyan; Stewart, Todd D.; Jin, Zhongmin; Wilcox, Ruth K.; Fisher, John

2013-01-01

Computational models of the natural hip joint are needed to examine and optimise tissue sparing interventions where the natural cartilage remains part of the bearing surfaces. Although the importance of interstitial fluid pressurisation in the performance of cartilage has long been recognized, few studies have investigated the time dependent interstitial fluid pressurisation in a three dimensional natural hip joint model. The primary aim of this study was to develop a finite element model of the natural hip incorporating the biphasic cartilage layers that was capable of simulating the joint response over a prolonged physiological loading period. An initial set of sensitivity studies were also undertaken to investigate the influence of hip size, clearance, cartilage properties, thickness and hemiarthroplasty on the contact mechanics of the joint. The contact stress, contact area, fluid pressure and fluid support ratio were calculated and cross-compared between models with different parameters to evaluate their influence. It was found that the model predictions for the period soon after loading were sensitive to the hip size, clearance, cartilage aggregate modulus, thickness and hemiarthroplasty, while the time dependent behaviour over 3000 s was influenced by the hip clearance and cartilage aggregate modulus, permeability, thickness and hemiarthroplasty. The modelling methods developed in this study provide a basic platform for biphasic simulation of the whole hip joint onto which more sophisticated material models or other input parameters could be added in the future. PMID:23664238

Discrepancies Between Blood Glucose and Interstitial Glucose—Technological Artifacts or Physiology: Implications for Selection of the Appropriate Therapeutic Target

PubMed Central

Siegmund, Thorsten; Heinemann, Lutz; Kolassa, Ralf; Thomas, Andreas

2017-01-01

Background: For decades, the major source of information used to make therapeutic decisions by patients with diabetes has been glucose measurements using capillary blood samples. Knowledge gained from clinical studies, for example, on the impact of metabolic control on diabetes-related complications, is based on such measurements. Different to traditional blood glucose measurement systems, systems for continuous glucose monitoring (CGM) measure glucose in interstitial fluid (ISF). The assumption is that glucose levels in blood and ISF are practically the same and that the information provided can be used interchangeably. Thus, therapeutic decisions, that is, the selection of insulin doses, are based on CGM system results interpreted as though they were blood glucose values. Methods: We performed a more detailed analysis and interpretation of glucose profiles obtained with CGM in situations with high glucose dynamics to evaluate this potentially misleading assumption. Results: Considering physical activity, hypoglycemic episodes, and meal-related differences between glucose levels in blood and ISF uncover clinically relevant differences that can make it risky from a therapeutic point of view to use blood glucose for therapeutic decisions. Conclusions: Further systematic and structured evaluation as to whether the use of ISF glucose is more safe and efficient when it comes to acute therapeutic decisions is necessary. These data might also have a higher prognostic relevance when it comes to long-term metabolic consequences of diabetes. In the long run, it may be reasonable to abandon blood glucose measurements as the basis for diabetes management and switch to using ISF glucose as the appropriate therapeutic target. PMID:28322063

A refractometry-based glucose analysis of body fluids.

PubMed

Zirk, Kai; Poetzschke, Harald

2007-05-01

In principle, refractometry appears to be a suitable method for the measurement of glucose concentrations in body fluids (such as blood and the intercellular fluid), even though the refractive index of the measured samples, as an additive property, is not specific. But, if certain conditions are fulfilled, the glucose content can be calculated using the refractive index in combination with values from a further measurement. This study describes the determination of the glucose content using refractometry in human blood serum derivates, which were selected - due to their ready availability - to be used as a model for interstitial fluid. Refractometry of body fluids requires the elimination of disturbing components from the measurement sample. First of all, a homogenous fluid (i.e. consisting of one phase) is required, so that all cells and components in suspension need to be separated out. Furthermore, certain dissolved macromolecular components which are known to disturb the measurement process must also be removed. In human serum samples which had been ultrafiltrated with a range of ultrafilters of different pore sizes, a comparative evaluation showed that only ultrafiltration through a filter with a separation limit of between 3 and 30kDa resulted in maximal reduction of the refractive index (compared to native serum), whereas ultrafilters with greater separation limits did not. The total content of osmotically active solutes (the tonicity) also exerts a clear influence. However, exemplary measurements in blood plasma fluid from one volunteer showed that the electrical conductivity is (without an additive component) directly proportional to the osmolality: physiological changes in the state of body hydration (hyperhydration and dehydration) do not lead to any considerable changes in the relation between ionised and uncharged solute particles, but instead result in a sufficiently clear dilution or concentration of the blood fluid's low molecular components. This finding allows the use of the--technically easy to measure--electrical conductivity as a measure for the tonicity of the measurement samples. Using measurements of these two parameters--refractive index and electrical conductivity--in blood serum obtained from a healthy volunteer, a two-dimensional calibration function (calibration matrix) for the assessment of the glucose content of ultrafiltrated human blood serum was constructed, and the measurement of blood glucose levels in non-diabetic (four females and four males) volunteers in comparison to a reference method was evaluated showing (as a proof of concept) a linear association. Assessment of the inaccuracy of these measurements made with the described measuring devices and methods showed a deviation from the reference values of less than 10%. An estimation of the maximum possible error showed relative deviations (maximum measurement uncertainties) of up to 20%.

Interstitial Photoacoustic Sensor for the Measurement of Tissue Temperature during Interstitial Laser Phototherapy

PubMed Central

Li, Zhifang; Chen, Haiyu; Zhou, Feifan; Li, Hui; Chen, Wei R.

2015-01-01

Photothermal therapy is an effective means to induce tumor cell death, since tumor tissue is more sensitive to temperature increases than normal tissue. Biological responses depend on tissue temperature; target tissue temperature needs to be precisely measured and controlled to achieve desired thermal effects. In this work, a unique photoacoustic (PA) sensor is proposed for temperature measurement during interstitial laser phototherapy. A continuous-wave laser light and a pulsed laser light, for photothermal irradiation and photoacoustic temperature measurement, respectively, were delivered to the target tissue through a fiber coupler. During laser irradiation, the PA amplitude was measured. The Grüneisen parameter and the bioheat equation were used to determine the temperature in strategic positions in the target tissue. Our results demonstrate that the interstitial PA amplitude is a linear function of temperature in the range of 22 to 55 °C, as confirmed by thermocouple measurement. Furthermore, by choosing appropriate laser parameters, the maximum temperature surrounding the active diffuse fiber tip in tissue can be controlled in the range of 41 to 55 °C. Thus, this sensor could potentially be used for fast, accurate, and convenient three-dimensional temperature measurement, and for real-time feedback and control of interstitial laser phototherapy in cancer treatment. PMID:25756865

The assessment of potentially interfering metabolites and dietary components in blood using an osmotic glucose sensor based on the concanavalin A-dextran affinity assay.

PubMed

Krushinitskaya, Olga; Tønnessen, Tor Inge; Jakobsen, Henrik; Johannessen, Erik

2011-10-15

Continuous surveillance of blood glucose is a prerogative of maintaining a tight glycaemic control in people suffering from diabetes mellitus. Implantable sensor technology offers the potential of conducting direct long term continuous glucose measurements, but current size restrictions and operational challenges have limited their applications. The osmotic sensor utilises diffusion to create a hydrostatic pressure that is independent of sensor operation and power consumption. This permits ultra-low power architectures to be realized with a minimal start-up time in a package suitable for miniaturization. In contrast, osmotic sensors suffer from the inability of their membranes to discriminate between different constituents in blood or the interstitial fluid that are of comparable size to glucose. By implementing an affinity assay based on the competitive bonding between concanavalin A and dextran, the selectivity of the membrane can be transferred to the glucose specific recognition of the affinity assay. The osmotic effect from the physiological levels of several key metabolites and nutritional components has been addressed identifying in particular ethanol, lactate and amino acids as potential interfering constituents. Both ascorbic acid and mannose would have a normal physiological concentration that is too low to be detected. The studies shows that an osmotic glucose sensor equipped with the con A-dextran affinity assay, is able to filter out potential interfering constituents present in blood, plasma and the interstitial fluid yet retaining a pressure that is proportional to glucose only. Copyright © 2011 Elsevier B.V. All rights reserved.

Interstitial matrix proteins determine hyaluronan reflection and fluid retention in rabbit joints: effect of protease

PubMed Central

Sabaratnam, S; Coleman, P J; Mason, R M; Levick, J R

2007-01-01

Hyaluronan (HA) retention inside the synovial cavity of joints serves diverse protective roles. We tested the hypothesis that HA retention is mediated by the network of extracellular matrix proteins in the synovial lining. Cannulated rabbit knee joints were infused with HA solution with or without pretreatment by chymopapain, a collagen-sparing protease. Trans-synovial fluid escape rate was measured and, after a period of trans-synovial filtration, samples of intra-articular fluid and subsynovial fluid were analysed for HA to assess its trans-synovial ultrafiltration. In control joints, HA ultrafiltration was confirmed by postfiltration increases in intra-articular HA concentration (259 ± 17% of infused concentration) and reduced subsynovial concentration (30 ± 8%; n = 11). The proportion of HA molecules reflected by the synovium was 57–75%. Chymopapain treatment increased the hydraulic permeability of the synovial lining ∼13-fold, almost abolished the trans-synovial difference in HA concentration and reduced the HA reflected fraction to 3–7% (n = 6; P < 0.001, ANOVA). Structural studies confirmed that chymopapain treatment depleted the matrix of proteoglycans but preserved its collagen. The findings thus demonstrate that HA ultrafiltration and synovial hydraulic permeability are determined by the network of non-collagen, extracellular matrix proteins. This may be important clinically, since protease activity is raised in rheumatoid arthritis, as are HA and fluid escape. PMID:17008373

Unravelling the effects of melt depletion and secondary infiltration on mantle Re-Os isotopes beneath the French Massif Central

NASA Astrophysics Data System (ADS)

Harvey, J.; Gannoun, A.; Burton, K. W.; Schiano, P.; Rogers, N. W.; Alard, O.

2010-01-01

Spinel lherzolite xenoliths from Mont Briançon, French Massif Central, retain evidence for multiple episodes of melt depletion and melt/fluid infiltration (metasomatism). Evidence for primary melt depletion is still preserved in the co-variation of bulk-rock major elements (MgO 38.7-46.1 wt.%; CaO 0.9-3.6 wt.%), and many samples yield unradiogenic bulk-rock Os isotope ratios ( 187Os/ 188Os = 0.11541-0.12626). However, many individual xenoliths contain interstitial glasses and melt inclusions that are not in equilibrium with the major primary minerals. Incompatible trace element mass balance calculations demonstrate that metasomatic components comprise a significant proportion of the bulk-rock budget for these elements in some rocks, ranging to as much as 25% of Nd and 40% of Sr Critically, for Re-Os geochronology, melt/fluid infiltration is accompanied by the mobilisation of sulfide. Consequently, bulk-rock isotope measurements, whether using lithophile (e.g. Rb-Sr, Sm-Nd) or siderophile (Re-Os) based isotope systems, may only yield a perturbed and/or homogenised average of these multiple events. Osmium mass balance calculations demonstrate that bulk-rock Os in peridotite is dominated by contributions from two populations of sulfide grain: (i) interstitial, metasomatic sulfide with low [Os] and radiogenic 187Os/ 188Os, and (ii) primary sulfides with high [Os] and unradiogenic 187Os/ 188Os, which have been preserved within host silicate grains and shielded from interaction with transient melts and fluid. The latter can account for >97% of bulk-rock Os and preserve geochronological information of the melt from which they originally precipitated as an immiscible liquid. The Re-depletion model ages of individual primary sulfide grains preserve evidence for melt depletion beneath the Massif Central from at least 1.8 Gyr ago despite the more recent metasomatic event(s).

[Extracellular fluid, plasma and interstitial volume in cirrhotic patients without clinical edema or ascites].

PubMed

Noguera Viñas, E C; Hames, W; Mothe, G; Barrionuevo, M P

1989-01-01

Extracellular fluid volume (E.C.F.) and plasma volume (P.V.), were measured with sodium sulfate labeled with 35I and 131I human serum albumin, respectively, by the dilution technique in control subjects and in cirrhotic patients without clinical ascites or edema, renal or hepatic failure, gastrointestinal bleeding or diuretics. Results are expressed as mean +/- DS in both ml/m2 and ml/kg. In normal subjects E.C.F. (n = 8) was 7,533 +/- 817 ml/m2 (201.3 +/- 182 ml/kg), P.V. (n = 11) 1,767 +/- 337 ml/m2 (47.2 +/- 9.3 ml/kg), and interstitial fluid (I.S.F.) (n = 7) 5,758 +/- 851 ml/m2 (Table 2). In cirrhotic patients E.C.F. (n = 11) was 10,318 +/- 2,980 ml/m2 (261.7 +/- 76.8 ml/kg), P.V. (n = 12) 2,649 +/- 558 ml/m2 (67.7 +/- 15.6 ml/kg) and I.S.F. (n = 11) 7,866 +/- 2,987 ml/m2 (Table 3). Cirrhotic patients compared with normal subjects have hypervolemia due to a significant E.C.F. and P.V. expansion (p less than 0.02 and less than 0.001 respectively) (Fig. 1). Reasons for E.C.F. and P.V. abnormalities in cirrhotic patients may reflect urinary sodium retention related to portal hipertension which stimulates aldosterone release or enhanced renal tubular sensitivity to the hormone. However, it is also possible that these patients, in the presence of hypoalbuminemia (Table 1), have no clinical edema or ascites due to increased glomerular filtration, suppressed release of vasopressin, increased natriuretic factor, and urinary prostaglandin excretion, in response to the intravascular expansion, all of which increased solute and water delivery to the distal nephron and improved renal water excretion. We conclude that in our clinical experience cirrhotic patients without ascites or edema have hypervolemia because of a disturbance in E.C.F.

A nonlinear model for myogenic regulation of blood flow to bone: equilibrium states and stability characteristics.

PubMed

Harrigan, T P

1996-01-01

A simple compartmental model for myogenic regulation of interstitial pressure in bone is developed, and the interaction between changes in interstitial pressure and changes in arterial and venous resistance is studied. The arterial resistance is modeled by a myogenic model that depends on transmural pressure, and the venous resistance is modeled by using a vascular waterfall. Two series capacitances model blood storage in the vascular system and interstitial fluid storage in the extravascular space. The static results mimic the observed effect that vasodilators work less well in bone than do vasoconstrictors. The static results also show that the model gives constant flow rates over a limited range of arterial pressure. The dynamic model shows unstable behavior at small values of bony capacitance and at high enough myogenic gain. At low myogenic gain, only a single equilibrium state is present, but a high enough myogenic gain, two new equilibrium states appear. At additional increases in gain, one of the two new states merges with and then separates from the original state, and the original state becomes a saddle point. The appearance of the new states and the transition of the original state to a saddle point do not depend on the bony capacitance, and these results are relevant to general fluid compartments. Numerical integration of the rate equations confirms the stability calculations and shows limit cycling behavior in several situations. The relevance of this model to circulation in bone and to other compartments is discussed.

Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy.

PubMed

Sullan, Molly J; Asken, Breton M; Jaffee, Michael S; DeKosky, Steven T; Bauer, Russell M

2018-01-01

Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interstitial water studies on small core samples, Leg 15

USGS Publications Warehouse

Sayles, Fred L.; Manheim, Frank T.; Waterman, Lee S.

1973-01-01

Analyses of pore fluids from reducing environments demonstrate that reduction of SO4 is accompanied by large increases in alkalinity and strong depletion of Ca and Mg. The data are compatible with a model of replacement of Fe3+ in clay lattices by Mg from the interstitial solutions and the precipitation of pyrite. Depletions of Na in the interstitial solutions are related to Mg losses by a ratio of approximately 1:3. Pore fluids from oxidizing pelagic sediments exhibit little SO4 depletion. Losses of Mg are accompanied by the addition of Ca to the pore solutions on a nearly 1:1 basis. Strong Sr enrichment is also found in these solutions. The magnitude of the Sr increase suggests that considerable carbonate recrystallization has occurred. As part of an extensive interlaboratory and analytical calibration, the effect of squeezing sediment at different temperatures has been studied in depth. Samples of a variety of lithologies have been included. Enrichment of K by as much as 24 percent and depletion of Mg and Ca by up to 7 percent occurs during warming. However, no significant effect upon Cl and SO4 could be detected. The strongest effects are seen in the minor constituents studied. On warming, Sr, Si, and B are enriched as much as 19, 40, and 60 percent, respectively. The size of the observed concentration changes varies with the mineralogy of the sediment, but is significant in all types studied, particularly with regards to Mg and K.

Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R

2018-06-05

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality. © RSNA, 2018 Online supplemental material is available for this article.

The intravascular volume effect of Ringer's lactate is below 20%: a prospective study in humans.

PubMed

Jacob, Matthias; Chappell, Daniel; Hofmann-Kiefer, Klaus; Helfen, Tobias; Schuelke, Anna; Jacob, Barbara; Burges, Alexander; Conzen, Peter; Rehm, Markus

2012-05-16

Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (for example, human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise. In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with Ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t tests (according to Student) for the singular measurements were taken. P < 0.05 was considered to be significant. A total of 1,097 ± 285 ml of whole blood were withdrawn (641 ± 155 ml/m(2) body surface area) and simultaneously replaced by 3,430 ± 806 ml of Ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459 ± 185 ml; P < 0.05) that did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+2,157 ± 606 ml; P < 0.05). The volume effect of Ringer's lactate was 17 ± 10%. The infusion of 245 ± 64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184 ± 63%. Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the three-fold amount of Ringer's lactate impedes maintenance of intravascular normovolemia. The main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the five-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous.

NOR-USA Scientific Traverse of East Antarctica: Science and Logistics on a Three-Month Expedition Across Antarctica's Farthest Frontier

NASA Technical Reports Server (NTRS)

Albert, Mary R.

2012-01-01

Dr. Albert's current research is centered on transfer processes in porous media, including air-snow exchange in the Polar Regions and in soils in temperate areas. Her research includes field measurements, laboratory experiments, and theoretical modeling. Mary conducts field and laboratory measurements of the physical properties of natural terrain surfaces, including permeability, microstructure, and thermal conductivity. Mary uses the measurements to examine the processes of diffusion and advection of heat, mass, and chemical transport through snow and other porous media. She has developed numerical models for investigation of a variety of problems, from interstitial transport to freezing of flowing liquids. These models include a two-dimensional finite element code for air flow with heat, water vapor, and chemical transport in porous media, several multidimensional codes for diffusive transfer, as well as a computational fluid dynamics code for analysis of turbulent water flow in moving-boundary phase change problems.

Latest advances in edema

NASA Technical Reports Server (NTRS)

Villavicencio, J. L.; Hargens, A. R.; Pikoulicz, E.

1996-01-01

Basic concepts in the physiopathology of edema are reviewed. The mechanisms of fluid exchange across the capillary endothelium are explained. Interstitial flow and lymph formation are examined. Clinical disorders of tissue and lymphatic transport, microcirculatory derangements in venous disorders, protein disorders, and lymphatic system disorders are explored. Techniques for investigational imaging of the lymphatic system are explained.

Nanoscale Viscoelasticity of Extracellular Matrix Proteins in Soft Tissues: a Multiscale Approach

PubMed Central

Miri, Amir K.; Heris, Hossein K.; Mongeau, Luc; Javid, Farhad

2013-01-01

We propose that the bulk viscoelasticity of soft tissues results from two length-scale-dependent mechanisms: the time-dependent response of extracellular matrix proteins (ECM) at the nanometer scale and the biophysical interactions between the ECM solid structure and interstitial fluid at the micrometer scale. The latter was modeled using the poroelasticity theory with an assumption of free motion of the interstitial fluid within the porous ECM structure. Following a recent study (Heris, H.K., Miri, A.K., Tripathy, U., Barthelat, F., Mongeau, L., 2013. Journal of the Mechanical Behavior of Biomedical Materials), atomic force microscopy was used to perform creep loading and 50-nm sinusoidal oscillations on porcine vocal folds. The proposed model was calibrated by a finite element model to accurately predict the nanoscale viscoelastic moduli of ECM. A linear correlation was observed between the in-depth distribution of the viscoelastic moduli and that of hyaluronic acids in the vocal fold tissue. We conclude that hyaluronic acids may regulate the vocal fold viscoelasticity at nanoscale. The proposed methodology offers a characterization tool for biomaterials used in vocal fold augmentations. PMID:24317493

Perfusion kinetics in human brain tumor with DCE-MRI derived model and CFD analysis.

PubMed

Bhandari, A; Bansal, A; Singh, A; Sinha, N

2017-07-05

Cancer is one of the leading causes of death all over the world. Among the strategies that are used for cancer treatment, the effectiveness of chemotherapy is often hindered by factors such as irregular and non-uniform uptake of drugs inside tumor. Thus, accurate prediction of drug transport and deposition inside tumor is crucial for increasing the effectiveness of chemotherapeutic treatment. In this study, a computational model of human brain tumor is developed that incorporates dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data into a voxelized porous media model. The model takes into account realistic transport and perfusion kinetics parameters together with realistic heterogeneous tumor vasculature and accurate arterial input function (AIF), which makes it patient specific. The computational results for interstitial fluid pressure (IFP), interstitial fluid velocity (IFV) and tracer concentration show good agreement with the experimental results. The computational model can be extended further for predicting the deposition of chemotherapeutic drugs in tumor environment as well as selection of the best chemotherapeutic drug for a specific patient. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oligomeric protein complexes of apolipoproteins stabilize the internal fluid environment of organism in redfins of the Tribolodon genus [Pisces; Cypriniformes, Cyprinidae].

PubMed

Andreeva, Alla M; Serebryakova, Marina V; Lamash, Nina E

2017-06-01

One of the most important functions of plasma proteins in vertebrates is their participation in osmotic homeostasis in the organism. Modern concepts about plasma proteins and their capillary filtration are based on a model of large monomeric proteins that are able to penetrate the interstitial space. At the same time, it was revealed that a considerable amount of oligomeric complexes are present in the low-molecular-weight (LM) protein fraction in the extracellular fluids of fishes. The functions of these complexes are unknown. In the present study, we investigated the LM-fraction proteins in the plasma and interstitial fluid (IF) of redfins of the genus Tribolodon. This fish alternatively spends parts of its life cycle in saline and fresh waters. We identified the protein Wap65, serpins and apolipoproteins in this fraction. By combining the methods of 2D-E under native and denaturing conditions with MALDI, we demonstrated that only apolipoproteins formed complexes. We showed that serum apolipoproteins (АроА-I, Аро-14) were present in the form of homooligomeric complexes that were dissociated with the release of monomeric forms of proteins in the course of capillary filtration to IF. Dissociation of homooligomers is not directly correlated with the change in salinity but is correlated with seasonal dynamics. We found that there was a significant decrease in the total protein concentration in IF relative to plasma. Therefore, we suggested that dissociation of homooligomeric complexes from various apolipoproteins supports the isoosmoticity of extracellular fluids relative to capillary wall stabilization through a fluid medium in fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Phenotypic heterogeneity in lung capillary and extra-alveolar endothelial cells. Increased extra-alveolar endothelial permeability is sufficient to decrease compliance.

PubMed

Lowe, Kevin; Alvarez, Diego; King, Judy; Stevens, Troy

2007-11-01

In acute respiratory distress syndrome, pulmonary vascular permeability increases, causing intravascular fluid and protein to move into the lung's interstitium. The classic model describing the formation of pulmonary edema suggests that fluid crossing the capillary endothelium is drawn by negative interstitial pressure into the potential space surrounding extra-alveolar vessels and, as interstitial pressure builds, is forced into the alveolar air space. However, the validity of this model is challenged by animal models of acute lung injury in which extra-alveolar vessels are more permeable than capillaries under a variety of conditions. In the current study, we sought to determine whether extravascular fluid accumulation can be produced because of increased permeability of either the capillary or extra-alveolar endothelium, and whether different pathophysiology results from such site-specific increases in permeability. We perfused isolated lungs with either the plant alkaloid thapsigargin, which increases extra-alveolar endothelial permeability, or with 4alpha-phorbol 12, 13-didecanoate, which increases capillary endothelial permeability. Both treatments produced equal increases in whole lung vascular permeability, but caused fluid accumulations in separate anatomical compartments. Light microscopy of isolated lungs showed that thapsigargin caused fluid cuffing of large vessels, while 4alpha-phorbol 12, 13-didecanoate caused alveolar flooding. Dynamic compliance was reduced in lungs with cuffing of large vessels, but not in lungs with alveolar flooding. Phenotypic differences between vascular segments resulted in site-specific increases in permeability, which have different pathophysiological outcomes. Our findings suggest that insults leading to acute respiratory distress syndrome may increase permeability in extra-alveolar or capillary vascular segments, resulting in different pathophysiological sequela.

Normal stresses in semiflexible polymer hydrogels

NASA Astrophysics Data System (ADS)

Vahabi, M.; Vos, Bart E.; de Cagny, Henri C. G.; Bonn, Daniel; Koenderink, Gijsje H.; MacKintosh, F. C.

2018-03-01

Biopolymer gels such as fibrin and collagen networks are known to develop tensile axial stress when subject to torsion. This negative normal stress is opposite to the classical Poynting effect observed for most elastic solids including synthetic polymer gels, where torsion provokes a positive normal stress. As shown recently, this anomalous behavior in fibrin gels depends on the open, porous network structure of biopolymer gels, which facilitates interstitial fluid flow during shear and can be described by a phenomenological two-fluid model with viscous coupling between network and solvent. Here we extend this model and develop a microscopic model for the individual diagonal components of the stress tensor that determine the axial response of semiflexible polymer hydrogels. This microscopic model predicts that the magnitude of these stress components depends inversely on the characteristic strain for the onset of nonlinear shear stress, which we confirm experimentally by shear rheometry on fibrin gels. Moreover, our model predicts a transient behavior of the normal stress, which is in excellent agreement with the full time-dependent normal stress we measure.

[Research advances of fluid bio-mechanics in bone].

PubMed

Chen, Zebin; Huo, Bo

2017-04-01

It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

Obstructive sleep apnea decreases central nervous system-derived proteins in the cerebrospinal fluid.

PubMed

Ju, Yo-El S; Finn, Mary Beth; Sutphen, Courtney L; Herries, Elizabeth M; Jerome, Gina M; Ladenson, Jack H; Crimmins, Daniel L; Fagan, Anne M; Holtzman, David M

2016-07-01

We hypothesized that one mechanism underlying the association between obstructive sleep apnea (OSA) and Alzheimer's disease is OSA leading to decreased slow wave activity (SWA), increased synaptic activity, decreased glymphatic clearance, and increased amyloid-β. Polysomnography and lumbar puncture were performed in OSA and control groups. SWA negatively correlated with cerebrospinal fluid (CSF) amyloid-β-40 among controls and was decreased in the OSA group. Unexpectedly, amyloid-β-40 was decreased in the OSA group. Other neuronally derived proteins, but not total protein, were also decreased in the OSA group, suggesting that OSA may affect the interaction between interstitial and cerebrospinal fluid. Ann Neurol 2016;80:154-159. © 2016 American Neurological Association.

Determination of fluid extraction and osmotic conductance sigma K in the lung with hypertonic NaCl infusion. I. Theory.

PubMed

Hunter, M; Lee, J

1992-11-01

A dispersion and extraction model of the lung is developed to assess how the infusion of hypertonic saline into the pulmonary artery changes the gravimetric density of pulmonary venous blood. The dispersion analysis is built on the indicator dilution curve measured for the pulmonary circulation. The extraction model consists of microvascular and interstitial compartments separated by a permeable pulmonary endothelium. Because the density of fluid extracted by the hypertonic disturbance is lower than the blood density, the extraction leads to a decrease in blood density. Two cases of fluid extraction are analyzed, a hypertonic infusion to elevate the osmotic pressure in the pulmonary arterial blood in the form of a step function and an infusion performed over a period of 1 sec. Both cases show that the dispersion significantly attenuates the changes in osmotic pressure and density as they are transported by the blood along the pulmonary vasculature. Because the model has taken into account the effect of dispersion and pulmonary blood flow, the equations developed here provide the basis to calculate from the density change in pulmonary venous blood the characteristics of osmotic extraction intrinsic to the lung.

Early Archean serpentine mud volcanoes at Isua, Greenland, as a niche for early life.

PubMed

Pons, Marie-Laure; Quitté, Ghylaine; Fujii, Toshiyuki; Rosing, Minik T; Reynard, Bruno; Moynier, Frederic; Douchet, Chantal; Albarède, Francis

2011-10-25

The Isua Supracrustal Belt, Greenland, of Early Archean age (3.81-3.70 Ga) represents the oldest crustal segment on Earth. Its complex lithology comprises an ophiolite-like unit and volcanic rocks reminiscent of boninites, which tie Isua supracrustals to an island arc environment. We here present zinc (Zn) isotope compositions measured on serpentinites and other rocks from the Isua supracrustal sequence and on serpentinites from modern ophiolites, midocean ridges, and the Mariana forearc. In stark contrast to modern midocean ridge and ophiolite serpentinites, Zn in Isua and Mariana serpentinites is markedly depleted in heavy isotopes with respect to the igneous average. Based on recent results of Zn isotope fractionation between coexisting species in solution, the Isua serpentinites were permeated by carbonate-rich, high-pH hydrothermal solutions at medium temperature (100-300 °C). Zinc isotopes therefore stand out as a pH meter for fossil hydrothermal solutions. The geochemical features of the Isua fluids resemble the interstitial fluids sampled in the mud volcano serpentinites of the Mariana forearc. The reduced character and the high pH inferred for these fluids make Archean serpentine mud volcanoes a particularly favorable setting for the early stabilization of amino acids.

Bed-rest studies: Fluid and electrolyte responses

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.

1983-01-01

Confinement in the horizontal position for 2 to 3 weeks results in a chronic decrease in plasma volume, increased interstitial fluid volume, and unchanged or slightly increased extracellular fluid volume. Concentrations of blood electrolytes, glucose, and nitrogenous constituents remain within normal limits of variability when maintenance levels of isometric or isotonic exercise are performed for 1 hr/day. Hematocrit and plasma osmolality can be elevated significantly throughout bed rest (BR). Significant diuresis occurs on the first day, and increases in urine Na and Ca continue throughout BR, although voluntary fluid intake is unchanged. Urine Na and K are evaluated during the second week of BR in spite of stabilization of PV and extracellular volume. The initial diuresis probably arises from the extracellular fluid while subsequent urine loss above control levels must come from the intracellular fluid. Preservation of the extracellular volume takes precedance over maintenance of the intracellular fluid volume. The functioning of a natriuretic factor (hormone) to account for the continued increased loss of Na in the urine is suggested.

Formation of edema and fluid shifts during a long-haul flight.

PubMed

Mittermayr, Markus; Fries, Dietmar; Innerhofer, Petra; Schobersberger, Beatrix; Klingler, Anton; Partsch, Hugo; Fischbach, Uwe; Gunga, Hanns-Christian; Koralewski, Eberhard; Kirsch, Karl; Schobersberger, Wolfgang

2003-01-01

More than 1.5 billion passengers travel by aircraft every year. Leg edema, as a sign of venous stasis, is a well-known problem among passengers during and after long-haul flights. Until now, no studies have been done on the development of leg edema and fluid shifts under real flight conditions. The aim of our study was to evaluate edema formation in the leg and to investigate possible fluid shifts to the interstitial space under real flight conditions. Twenty participants, 10 without risk and 10 with moderate risk for venous thrombosis, were selected. They flew from Vienna to Washington, flight time 9 h, and returned 2 days later. Investigations were done 48 h before the flight, between the fifth and eighth flight hour on board to Washington and back to Vienna, immediately after arrival in Vienna, and 1 and 3 days after arrival. Plethysmographic measurements were carried out using an optoelectronic scanner system (Perometer). Thickness of the skin was measured at the forehead and in front of the tibia. There were no differences in all measurements between both groups. The volume of the leg increased from 8242 +/- 1420 mL to 8496 +/- 1474 mL after the flight (p <.001). Volume accumulation was distributed to the lower leg as well as to the thigh. Skin thickness in front of the tibia increased significantly during the flight (p <.05), and remained elevated 1 day after arrival. We have demonstrated that long-haul flights induce significant fluid accumulation in the lower extremity, involving the lower leg and thigh. This increase in tissue thickness was maintained for some days after the flights.

Review: Tau in biofluids - relation to pathology, imaging and clinical features.

PubMed

Zetterberg, H

2017-04-01

Tau is a microtubule-binding protein that is important for the stability of neuronal axons. It is normally expressed within neurons and is also secreted into the brain interstitial fluid that communicates freely with cerebrospinal fluid (CSF) and, in a more restricted manner, blood via the glymphatic clearance system of the brain. In Alzheimer's disease (AD), neuroaxonal degeneration results in increased release of tau from neurons. Furthermore, tau is truncated and phosphorylated, which leads to aggregation of tau in neurofibrillary tangles of the proximal axoplasm. Neuroaxonal degeneration and tangle formation are reflected by increased concentrations of total tau (T-tau, measured using assays that detect most forms of tau) and phospho-tau (P-tau, measured using assays with antibodies specific to phosphorylated forms of tau). In AD CSF, both T-tau and P-tau concentrations are increased. In stroke and other CNS disorders with neuroaxonal injury but without tangles, T-tau is selectively increased, whereas P-tau concentration often stays normal. In tauopathies (diseases with both neurodegeneration and neurofibrillary tangles) other than AD, CSF T-tau and P-tau concentrations are typically unaltered, which is a puzzling result that warrants further investigation. In the current review, I discuss the association of T-tau and P-tau concentrations in body fluids with neuropathological changes, imaging findings and clinical features in AD and other CNS diseases. © 2017 British Neuropathological Society.

Monte Carlo simulation of non-invasive glucose measurement based on FMCW LIDAR

NASA Astrophysics Data System (ADS)

Xiong, Bing; Wei, Wenxiong; Liu, Nan; He, Jian-Jun

2010-11-01

Continuous non-invasive glucose monitoring is a powerful tool for the treatment and management of diabetes. A glucose measurement method, with the potential advantage of miniaturizability with no moving parts, based on the frequency modulated continuous wave (FMCW) LIDAR technology is proposed and investigated. The system mainly consists of an integrated near-infrared tunable semiconductor laser and a detector, using heterodyne technology to convert the signal from time-domain to frequency-domain. To investigate the feasibility of the method, Monte Carlo simulations have been performed on tissue phantoms with optical parameters similar to those of human interstitial fluid. The simulation showed that the sensitivity of the FMCW LIDAR system to glucose concentration can reach 0.2mM. Our analysis suggests that the FMCW LIDAR technique has good potential for noninvasive blood glucose monitoring.

Non-invasive, Contrast-enhanced Spectral Imaging of Breast Cancer Signatures in Preclinical Animal Models In vivo

PubMed Central

Ramanujan, V Krishnan; Ren, Songyang; Park, Sangyong; Farkas, Daniel L

2011-01-01

We report here a non-invasive multispectral imaging platform for monitoring spectral reflectance and fluorescence images from primary breast carcinoma and metastatic lymph nodes in preclinical rat model in vivo. The system is built around a monochromator light source and an acousto-optic tunable filter (AOTF) for spectral selection. Quantitative analysis of the measured reflectance profiles in the presence of a widely-used lymphazurin dye clearly demonstrates the capability of the proposed imaging platform to detect tumor-associated spectral signatures in the primary tumors as well as metastatic lymphatics. Tumor-associated changes in vascular oxygenation and interstitial fluid pressure are reasoned to be the physiological sources of the measured reflectance profiles. We also discuss the translational potential of our imaging platform in intra-operative clinical setting. PMID:21572915

A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

PubMed Central

Fan, Lixia; Pei, Shaopeng; Lucas Lu, X; Wang, Liyun

2016-01-01

The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies. PMID:27722020

The choice of amniotic fluid in metabolomics for the monitoring of fetus health.

PubMed

Palmas, Francesco; Fattuoni, Claudia; Noto, Antonio; Barberini, Luigi; Dessì, Angelica; Fanos, Vassilios

2016-01-01

Amniotic fluid (AF) is a biological fluid in which metabolite transport is regulated by the placenta, the permeable skin, fetal lung egress and gastric fluid. During pregnancy, the composition of AF changes from similar to the interstitial fluid of the mother, to a more complex system, influenced by the fetus's urine. Since AF reflects the mother's and the fetus's health status at the same time, it may be an important diagnostic tool for a wider spectrum of clinical conditions. Indeed, the metabolic characterization of AF in relation to pathological occurrences may lead to the discovery of new biomarkers for a better clinical practice. For this reason, metabolomics may be the most suitable strategy for this task. In this review, research works on metabolomic AF analysis are discussed according to the morbidity of interest, being preterm birth/labor, gestational age and diabetes and fetal malformations, along with a number of other important studies.

A two-fluid model for avalanche and debris flows.

PubMed

Pitman, E Bruce; Le, Long

2005-07-15

Geophysical mass flows--debris flows, avalanches, landslides--can contain O(10(6)-10(10)) m(3) or more of material, often a mixture of soil and rocks with a significant quantity of interstitial fluid. These flows can be tens of meters in depth and hundreds of meters in length. The range of scales and the rheology of this mixture presents significant modelling and computational challenges. This paper describes a depth-averaged 'thin layer' model of geophysical mass flows containing a mixture of solid material and fluid. The model is derived from a 'two-phase' or 'two-fluid' system of equations commonly used in engineering research. Phenomenological modelling and depth averaging combine to yield a tractable set of equations, a hyperbolic system that describes the motion of the two constituent phases. If the fluid inertia is small, a reduced model system that is easier to solve may be derived.

Distribution of crystalloid fluid changes with the rate of infusion: a population-based study.

PubMed

Hahn, R G; Drobin, D; Zdolsek, J

2016-05-01

Crystalloid fluid requires 30 min for complete distribution throughout the extracellular fluid space and tends to cause long-standing peripheral edema. A kinetic analysis of the distribution of Ringer's acetate with increasing infusion rates was performed to obtain a better understanding of these characteristics of crystalloids. Data were retrieved from six studies in which 76 volunteers and preoperative patients had received between 300 ml and 2375 ml of Ringer's acetate solution at a rate of 20-80 ml/min (0.33-0.83 ml/min/kg). Serial measurements of the blood hemoglobin concentration were used as inputs in a kinetic analysis based on a two-volume model with micro-constants, using software for nonlinear mixed effects. The micro-constants describing distribution (k12) and elimination (k10) were unchanged when the rate of infusion increased, with half-times of 16 and 26 min, respectively. In contrast, the micro-constant describing how rapidly the already distributed fluid left the peripheral space (k21) decreased by 90% when the fluid was infused more rapidly, corresponding to an increase in the half-time from 3 to 30 min. The central volume of distribution (V(c)) doubled. The return of Ringer's acetate from the peripheral fluid compartment to the plasma was slower with high than with low infusion rates. Edema is a normal consequence of plasma volume expansion with this fluid, even in healthy volunteers. The results are consistent with the view that the viscoelastic properties of the interstitial matrix are responsible for the distribution and redistribution characteristics of crystalloid fluid. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Studies of O18 impurity trapping at interstitial dislocation loops in ion implanted Fe (1 1 0) by ion channeling and ab initio calculations

NASA Astrophysics Data System (ADS)

Mathayan, Vairavel; Kothalamuthu, Saravanan; Gnanasekaran, Jaiganesh; Balakrishnan, Sundaravel; Panigrahi, Binaykumar

2018-01-01

The O18 and self ions are implanted at same depth in Fe (1 1 0) crystal and annealed to study the oxygen trapping under excess self interstitial defects. Rutherford backscattering spectrometry, nuclear reaction analysis and channeling measurements have been performed to determine the lattice site position of O18. The presence of dislocation loops is confirmed by energy-dependent dechanneling parameter measurements. From the tilt angular scans of Fe and O18 signals along 〈1 0 0〉, 〈1 1 0〉 axes, O18 is found to be displaced 0.2 Å from tetrahedral towards octahedral interstitial site in O18. Similar lattice site location of oxygen with the displacement of 0.37 Å is predicted by density functional theory calculations for the interaction of oxygen with 〈1 0 0〉 interstitial dislocation loop structure. Our results provide strong evidence on oxygen trapping at interstitial dislocation loops in the presence of excess interstitial defects in iron.

Feasibility of interstitial diffuse optical tomography using cylindrical diffusing fiber for prostate PDT

PubMed Central

Liang, Xing; Wang, Ken Kang-Hsin; Zhu, Timothy C.

2013-01-01

Interstitial diffuse optical tomography (DOT) has been used to characterize spatial distribution of optical properties for prostate photodynamic therapy (PDT) dosimetry. We have developed an interstitial DOT method using cylindrical diffuse fibers (CDFs) as light sources, so that the same light sources can be used for both DOT measurement and PDT treatment. In this novel interstitial CDF-DOT method, absolute light fluence per source strength (in unit of 1/cm2) is used to separate absorption and scattering coefficients. A mathematical phantom and a solid prostate phantom including anomalies with known optical properties were used, respectively, to test the feasibility of reconstructing optical properties using interstitial CDF-DOT. Three dimension spatial distributions of the optical properties were reconstructed for both scenarios. Our studies show that absorption coefficient can be reliably extrapolated while there are some cross talks between absorption and scattering properties. Even with the suboptimal reduced scattering coefficients, the reconstructed light fluence rate agreed with the measured values to within ±10%, thus the proposed CDF-DOT allows greatly improved light dosimetry calculation for interstitial PDT. PMID:23629149

The Paravascular Pathway for Brain Waste Clearance: Current Understanding, Significance and Controversy

PubMed Central

Bacyinski, Andrew; Xu, Maosheng; Wang, Wei; Hu, Jiani

2017-01-01

The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted. PMID:29163074

A new glaucoma hypothesis: a role of glymphatic system dysfunction.

PubMed

Wostyn, Peter; Van Dam, Debby; Audenaert, Kurt; Killer, Hanspeter Esriel; De Deyn, Peter Paul; De Groot, Veva

2015-06-29

In a recent review article titled "A new look at cerebrospinal fluid circulation", Brinker et al. comprehensively described novel insights from molecular and cellular biology as well as neuroimaging research, which indicate that cerebrospinal fluid (CSF) physiology is much more complex than previously believed. The glymphatic system is a recently defined brain-wide paravascular pathway for CSF and interstitial fluid exchange that facilitates efficient clearance of interstitial solutes, including amyloid-β, from the brain. Although further studies are needed to substantiate the functional significance of the glymphatic concept, one implication is that glymphatic pathway dysfunction may contribute to the deficient amyloid-β clearance in Alzheimer's disease. In this paper, we review several lines of evidence suggesting that the glymphatic system may also have potential clinical relevance for the understanding of glaucoma. As a clinically acceptable MRI-based approach to evaluate glymphatic pathway function in humans has recently been developed, a unique opportunity now exists to investigate whether suppression of the glymphatic system contributes to the development of glaucoma. The observation of a dysfunctional glymphatic system in patients with glaucoma would provide support for the hypothesis recently proposed by our group that CSF circulatory dysfunction may play a contributory role in the pathogenesis of glaucomatous damage. This would suggest a new hypothesis for glaucoma, which, just like Alzheimer's disease, might be considered then as an imbalance between production and clearance of neurotoxins, including amyloid-β.

Microfluidic enhancement of intramedullary pressure increases interstitial fluid flow and inhibits bone loss in hindlimb suspended mice.

PubMed

Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

2010-08-01

Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process.

The influence of size, clearance, cartilage properties, thickness and hemiarthroplasty on the contact mechanics of the hip joint with biphasic layers.

PubMed

Li, Junyan; Stewart, Todd D; Jin, Zhongmin; Wilcox, Ruth K; Fisher, John

2013-06-21

Computational models of the natural hip joint are needed to examine and optimise tissue sparing interventions where the natural cartilage remains part of the bearing surfaces. Although the importance of interstitial fluid pressurisation in the performance of cartilage has long been recognized, few studies have investigated the time dependent interstitial fluid pressurisation in a three dimensional natural hip joint model. The primary aim of this study was to develop a finite element model of the natural hip incorporating the biphasic cartilage layers that was capable of simulating the joint response over a prolonged physiological loading period. An initial set of sensitivity studies were also undertaken to investigate the influence of hip size, clearance, cartilage properties, thickness and hemiarthroplasty on the contact mechanics of the joint. The contact stress, contact area, fluid pressure and fluid support ratio were calculated and cross-compared between models with different parameters to evaluate their influence. It was found that the model predictions for the period soon after loading were sensitive to the hip size, clearance, cartilage aggregate modulus, thickness and hemiarthroplasty, while the time dependent behaviour over 3000s was influenced by the hip clearance and cartilage aggregate modulus, permeability, thickness and hemiarthroplasty. The modelling methods developed in this study provide a basic platform for biphasic simulation of the whole hip joint onto which more sophisticated material models or other input parameters could be added in the future. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vascular, glial, and lymphatic immune gateways of the central nervous system.

PubMed

Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

2016-09-01

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

PubMed Central

Dantzler, William H.; Pannabecker, Thomas L.

2012-01-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter.

PubMed

Layton, Anita T; Dantzler, William H; Pannabecker, Thomas L

2012-03-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na(+) or urea-Cl(-) cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na(+) or urea- Cl(-) cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

Polycystic kidney disease in a European roe deer (Capreolus capreolus).

PubMed

Blutke, Andreas; März, Kristian; Matenaers, Cyrill; Oswald, Karl; Hermanns, Walter; Wanke, Rüdiger

2013-06-01

A severe case of polycystic nephropathy was seen in an adult European roe deer (Capreolus capreolus), culled in a German hunting district. The doe had bilaterally drastically enlarged kidneys, completely riddled with variably sized, fluid-filled cysts of up to 4 cm in diameter. Histopathologic and ultrastructural examination revealed disseminated formation of cysts with flattened epithelial cell linings in the entire renal parenchyma, as well as severe dilations of renal tubules, marked interstitial fibrosis, nephron atrophy, and chronic interstitial lymphoplasmacytic infiltrations in the intercystic kidney tissue. These morphologic findings most likely resemble the hallmarks of autosomal dominant polycystic disease in humans, and present the first detailed description of a case of polycystic kidney disease in a roe deer.

Deriving sediment Interstitial Water Remediation Goals (IWRGs) for the protection of benthic organisms from direct toxicity

EPA Science Inventory

Background/Objectives. Passive sampling is becoming a frequently used measurement technique at Superfund sites with contaminated sediments. Passive sampling measures the concentrations of freely dissolved chemicals (Cfrees) in the sediment interstitial water. The freely dissol...

Analysis of Dissolved Organic Nutrients in the Interstitial Water of Natural Biofilms.

PubMed

Tsuchiya, Yuki; Eda, Shima; Kiriyama, Chiho; Asada, Tomoya; Morisaki, Hisao

2016-07-01

In biofilms, the matrix of extracellular polymeric substances (EPSs) retains water in the interstitial region of the EPS. This interstitial water is the ambient environment for microorganisms in the biofilms. The nutrient condition in the interstitial water may affect microbial activity in the biofilms. In the present study, we measured the concentrations of dissolved organic nutrients, i.e., saccharides and proteins, contained in the interstitial water of biofilms formed on the stones. We also analyzed the molecular weight distribution, chemical species, and availability to bacteria of some saccharides in the interstitial water. Colorimetric assays showed that the concentrations of saccharides and proteins in the biofilm interstitial water were significantly higher (ca. 750 times) than those in the surrounding lake waters (p < 0.05). Chromatographic analyses demonstrated that the saccharides in the interstitial waters were mainly of low molecular-weight saccharides such as glucose and maltose, while proteins in the interstitial water were high molecular-weight proteins (over 7000 Da). Bacterial growth and production of EPS occurred simultaneously with the decrease in the low molecular-weight saccharide concentrations when a small portion of biofilm suspension was inoculated to the collected interstitial water, suggesting that the dissolved saccharides in the interstitial water support bacterial growth and formation of biofilms.

Evolution of anisotropy in bcc Fe distorted by interstitial boron

NASA Astrophysics Data System (ADS)

Gölden, Dominik; Zhang, Hongbin; Radulov, Iliya; Dirba, Imants; Komissinskiy, Philipp; Hildebrandt, Erwin; Alff, Lambert

2018-01-01

The evolution of magnetic anisotropy in bcc Fe as a function of interstitial boron atoms was investigated in thin films grown by molecular beam epitaxy. The thermodynamic nonequilibrium conditions during film growth allowed one to stabilize an interstitial boron content of about 14 at .% accompanied by lattice tetragonalization. The c /a ratio scaled linearly with the boron content up to a maximum value of 1.05 at 300 °C substrate growth temperature, with a room-temperature magnetization of. In contrast to nitrogen interstitials, the magnetic easy axis remained in-plane with an anisotropy of approximately -5.1 ×106erg /cm3 . Density functional theory calculations using the measured lattice parameters confirm this value and show that boron local ordering indeed favors in-plane magnetization. Given the increased temperature stability of boron interstitials as compared to nitrogen interstitials, this study will help to find possible ways to manipulate boron interstitials into a more favorable local order.

Pancreas tumor interstitial pressure catheter measurement

NASA Astrophysics Data System (ADS)

Nieskoski, Michael D.; Gunn, Jason; Marra, Kayla; Trembly, B. Stuart; Pogue, Brian W.

2016-03-01

This paper highlights the methodology in measuring interstitial pressure in pancreatic adenocarcinoma tumors. A Millar Mikrotip pressure catheter (SPR-671) was used in this study and a system was built to amplify and filter the output signal for data collection. The Millar pressure catheter was calibrated prior to each experiment in a water column at 37°C, range of 0 to 60 inH2O (112 mmHg), resulting in a calibration factor of 33 mV / 1 inH2O. The interstitial pressures measured in two orthotopically grown pancreatic adenocarcinoma tumor were 57 mmHg and 48 mmHg, respectively. Verteporfin uptake into the pancreatic adenocarcinoma tumor was measured using a probe-based experimental dosimeter.

MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor

PubMed Central

Magdoom, Kulam Najmudeen; Pishko, Gregory L.; Rice, Lori; Pampo, Chris; Siemann, Dietmar W.; Sarntinoranont, Malisa

2014-01-01

Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors. PMID:24619021

Interstitial water studies on small core samples, Deep Sea Drilling Project, Leg 5

USGS Publications Warehouse

Manheim, F. T.; Chan, K.M.; Sayles, F.L.

1970-01-01

Leg 5 samples fall into two categories with respect to interstitial water composition: 1) rapidly deposited terrigenous or appreciably terrigenous deposits, such as in Hole 35 (western Escanaba trough, off Cape Mendocino, California); and, 2) slowly deposited pelagic clays and biogenic muds and oozes. Interstitial waters in the former show modest to slight variations in chloride and sodium, but drastic changes in non-conservative ions such as magnesium and sulfate. The pelagic deposits show only relatively minor changes in both conservative and non-conservative pore fluid constituents. As was pointed out in earlier Leg Reports, it is believed that much of the variation in chloride in pore fluids within individual holes is attributable to the manipulation of samples on board ship and in the laboratory. On the other hand, the scatter in sodium is due in part to analytical error (on the order of 2 to 3 per cent, in terms of a standard deviation), and it probably accounts for most of the discrepancies in total anion and cation balance. All constituents reported here, with the exception of bulk water content, were analyzed on water samples which were sealed in plastic tubes aboard ship and were subsequently opened and divided into weighed aliquots in the laboratory. Analytical methods follow the atomic absorption, wet chemical and emission spectrochemical techniques briefly summarized in previous reports, e.g. Manheim et al., 1969, and Chan and Manheim, 1970. The authors acknowledge assistance from W. Sunda, D. Kerr, C. Lawson and H. Richards, and thank D. Spencer, P. Brewer and E. Degens for allowing the use of equipment and laboratory facilities.

Impairment of paravascular clearance pathways in the aging brain

PubMed Central

Kress, Benjamin T.; Iliff, Jeffrey J.; Xia, Maosheng; Wang, Minghuan; Wei, Helen; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason; Plog, Benjamin A.; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-01-01

Objective In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2–3 month), middle age (10–12 month) and old (18–20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence. Results Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. Interpretation We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. PMID:25204284

Impairment of paravascular clearance pathways in the aging brain.

PubMed

Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-12-01

In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

Percutaneous excretion of iron and ferritin (through Al-hijamah) as a novel treatment for iron overload in beta-thalassemia major, hemochromatosis and sideroblastic anemia.

PubMed

El Sayed, Salah Mohamed; Abou-Taleb, Ashraf; Mahmoud, Hany Salah; Baghdadi, Hussam; Maria, Reham A; Ahmed, Nagwa Sayed; Nabo, Manal Mohamed Helmy

2014-08-01

Iron overload is a big challenge when treating thalassemia (TM), hemochromatosis and sideroblastic anemia. It persists even after cure of TM with bone marrow transplantation. Iron overload results from increased iron absorption and repeated blood transfusions causing increased iron in plasma and interstitial fluids. Iron deposition in tissues e.g. heart, liver, endocrine glands and others leads to tissue damage and organ dysfunction. Iron chelation therapy and phlebotomy for iron overload have treatment difficulties, side effects and contraindications. As mean iron level in skin of TM patients increases by more than 200%, percutaneous iron excretion may be beneficial. Wet cupping therapy (WCT) is a simple, safe and economic treatment. WCT is a familiar treatment modality in some European countries and in Chinese hospitals in treating different diseases. WCT was reported to clear both blood plasma and interstitial spaces from causative pathological substances (CPS). Standard WCT method is Al-hijamah (cupping, puncturing and cupping, CPC) method of WCT that was reported to clear blood and interstitial fluids better than the traditional WCT (puncturing and cupping method, PC method of WCT). In other word, traditional WCT may be described as scarification and suction method (double S technique), while Al-hijamah may be described as suction, scarification and suction method (triple S technique). Al-hijamah is a more comprehensive treatment modality that includes all steps and therapeutic benefits of traditional dry cupping therapy and WCT altogether according to the evidence-based Taibah mechanism (Taibah theory). During the first cupping step of Al-hijamah, a fluid mixture is collected inside skin uplifting due to the effect of negative pressure inside sucking cups. This fluid mixture contains collected interstitial fluids with CPS (iron, ferritin and hemolyzed RBCs in thalassemia), filtered fluids (from blood capillaries) with iron and hemolyzed blood cells (hemolyzed RBCs, WBCs and platelets). That fluid mixture does not contain intact blood cells (having diameters in microns) that are too big to pass through pores of skin capillaries (6-12nm in diameter) and cannot be filtered. Puncturing skin upliftings and applying second cupping step excrete collected fluids. Skin scarifications (shartat mihjam in Arabic) should be small, superficial (0.1mm in depth), short (1-2mm in length), multiple, evenly distributed and confined to skin upliftings. Sucking pressure inside cups (-150 to -420mmHg) applied to skin is transmitted to around skin capillaries to be added to capillary hydrostatic pressure (-33mmHg at arterial end of capillaries and -13mmHg at venous end of capillaries) against capillary osmotic pressure (+20mmHg). This creates a pressure gradient and a traction force across skin and capillaries and increases filtration at arterial end of capillaries at net pressure of -163 to -433mmHg and at venous end of capillaries at net pressure of -143 to -413mmHg resulting in clearance of blood from CPS (iron, ferritin and hemolyzed blood cells). Net filtration pressure at renal glomeruli is 10mmHg i.e. Al-hijamah exerts a more pressure-dependent filtration than renal glomeruli. Al-hijamah may benefit patients through inducing negative iron balance. Interestingly, Al-hijamah was reported to decrease serum ferritin significantly (by about 22%) in healthy subjects while excessive traditional WCT was reported to cause iron deficiency anemia. Al-hijamah is a highly recommended treatment in prophetic medicine. In conclusion, Al-hijamah may be a promising adjuvant treatment for iron overload in TM, hemochromatosis and sideroblastic anemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia.

PubMed

Steil, G M; Rebrin, K; Hariri, F; Jinagonda, S; Tadros, S; Darwin, C; Saad, M F

2005-09-01

Glucose sensors often measure s.c. interstitial fluid (ISF) glucose rather than blood or plasma glucose. Putative differences between plasma and ISF glucose include a protracted delay during the recovery from hypoglycaemia and an increased gradient during hyperinsulinaemia. These have often been investigated using sensor systems that have delays due to signal smoothing, or require long equilibration times. The aim of the present study was to define these relationships during hypoglycaemia in a well-equilibrated system with no smoothing. Hypoglycaemia was induced by i.v. insulin infusion (360 pmol.m(-2).min(-1)) in ten non-diabetic subjects. Glucose was sequentially clamped at approximately 5, 4.2 and 3.1 mmol/l and allowed to return to normoglycaemia. Subjects wore two s.c. glucose sensors (Medtronic MiniMed, Northridge, CA, USA) that had been inserted for more than 12 h. A two-compartment model was used to quantify the delay and gradient. The delay during the fall in plasma glucose was not different from the delay during recovery (8.3+/-0.67 vs 6.3+/-1.1 min; p=0.27) and no differences were observed in the ratio of sensor current to plasma glucose at basal insulin (2.7+/-0.25 nA.mmol(-1).l) compared with any of the hyperinsulinaemic clamp phases (2.8+/-0.18, 2.7+/-0.021, 2.9+/-0.21; p=NS). The ratio was significantly elevated following recovery to normoglycaemia (3.1+/-0.2 nA.mmol(-1).l; p<0.001). The elevated ratio suggests that the plasma to ISF glucose gradient was decreased following hypoglycaemia, possibly due to increased skin blood flow. Recovery from hypoglycaemia is not accompanied by a protracted delay and insulin does not increase the plasma to s.c. ISF glucose gradient.

Cells competition in tumor growth poroelasticity

NASA Astrophysics Data System (ADS)

Fraldi, Massimiliano; Carotenuto, Angelo R.

2018-03-01

Growth of biological tissues has been recently treated within the framework of Continuum Mechanics, by adopting heterogeneous poroelastic models where the interaction between soft matrix and interstitial fluid flow is coupled with inelastic effects ad hoc introduced to simulate the macroscopic volumetric growth determined by cells division, cells growth and extracellular matrix changes occurring at the micro-scale level. These continuum models seem to overcome some limitations intrinsically associated to other alternative approaches based on mass balances in multiphase systems, because the crucial role played by residual stresses accompanying growth and nutrients walkway is preserved. Nevertheless, when these strategies are applied to analyze solid tumors, mass growth is usually assigned in a prescribed form that essentially copies the in vitro measured intrinsic growth rates of the cell species. As a consequence, some important cell-cell dynamics governing mass evolution and invasion rates of cancer cells, as well as their coupling with feedback mechanisms associated to in situ stresses, are inevitably lost and thus the spatial distribution and the evolution with time of the growth inside the tumor -which would be results rather than inputs- are forced to enter in the model simply as data. In order to solve this paradox, it is here proposed an enhanced multi-scale poroelastic model undergoing large deformations and embodying inelastic growth, where the net growth terms directly result from the "interspecific" predator-prey (Volterra/Lotka-like) competition occurring at the micro-scale level between healthy and abnormal cell species. In this way, a system of fully-coupled non-linear PDEs is derived to describe how the fight among cell species to grab the available common resources, stress field, pressure gradients, interstitial fluid flows driving nutrients and inhomogeneous growth all simultaneously interact to decide the tumor fate.

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer.

PubMed

Yang, Lijun; Kress, Benjamin T; Weber, Harris J; Thiyagarajan, Meenakshisundaram; Wang, Baozhi; Deane, Rashid; Benveniste, Helene; Iliff, Jeffrey J; Nedergaard, Maiken

2013-05-01

Neurodegenerative diseases such as Alzheimer's are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30-180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans.

Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracer

PubMed Central

2013-01-01

Background Neurodegenerative diseases such as Alzheimer’s are associated with the aggregation of endogenous peptides and proteins that contribute to neuronal dysfunction and loss. The glymphatic system, a brain-wide perivascular pathway along which cerebrospinal fluid (CSF) and interstitial fluid (ISF) rapidly exchange, has recently been identified as a key contributor to the clearance of interstitial solutes from the brain, including amyloid β. These findings suggest that measuring changes in glymphatic pathway function may be an important prognostic for evaluating neurodegenerative disease susceptibility or progression. However, no clinically acceptable approach to evaluate glymphatic pathway function in humans has yet been developed. Methods Time-sequenced ex vivo fluorescence imaging of coronal rat and mouse brain slices was performed at 30–180 min following intrathecal infusion of CSF tracer (Texas Red- dextran-3, MW 3 kD; FITC- dextran-500, MW 500 kD) into the cisterna magna or lumbar spine. Tracer influx into different brain regions (cortex, white matter, subcortical structures, and hippocampus) in rat was quantified to map the movement of CSF tracer following infusion along both routes, and to determine whether glymphatic pathway function could be evaluated after lumbar intrathecal infusion. Results Following lumbar intrathecal infusions, small molecular weight TR-d3 entered the brain along perivascular pathways and exchanged broadly with the brain ISF, consistent with the initial characterization of the glymphatic pathway in mice. Large molecular weight FITC-d500 remained confined to the perivascular spaces. Lumbar intrathecal infusions exhibited a reduced and delayed peak parenchymal fluorescence intensity compared to intracisternal infusions. Conclusion Lumbar intrathecal contrast delivery is a clinically useful approach that could be used in conjunction with dynamic contrast enhanced MRI nuclear imaging to assess glymphatic pathway function in humans. PMID:23635358

3-compartment talaporfin sodium pharmacokinetic model by optimization using fluorescence measurement data from canine skin to estimate the concentration in interstitial space

NASA Astrophysics Data System (ADS)

Uno, Yuko; Ogawa, Emiyu; Aiyoshi, Eitaro; Arai, Tsunenori

2018-02-01

We constructed the 3-compartment talaporfin sodium pharmacokinetic model for canine by an optimization using the fluorescence measurement data from canine skin to estimate the concentration in the interstitial space. It is difficult to construct the 3-compartment model consisted of plasma, interstitial space, and cell because there is a lack of the dynamic information. Therefore, we proposed the methodology to construct the 3-compartment model using the measured talaporfin sodium skin fluorescence change considering originated tissue part by a histological observation. In a canine animal experiment, the talaporfin sodium concentration time history in plasma was measured by a spectrophotometer with a prepared calibration curve. The time history of talaporfin sodium Q-band fluorescence on left femoral skin of a beagle dog excited by talaporfin sodium Soret-band of 409 nm was measured in vivo by our previously constructed measurement system. The measured skin fluorescence was classified to its source, that is, specific ratio of plasma, interstitial space, and cell. We represented differential rate equations of the talaporfin sodium concentration in plasma, interstitial space, cell. The specific ratios and a converting constant to obtain absolute value of skin concentration were arranged. Minimizing the squared error of the difference between the measured fluorescence data and calculated concentration by the conjugate gradient method in MATLAB, the rate constants in the 3-compartment model were determined. The accuracy of the fitting operation was confirmed with determination coefficient of 0.98. We could construct the 3-compartment pharmacokinetic model for canine using the measured talaporfin sodium fluorescence change from canine skin.

An arbitrary Lagrangian–Eulerian finite element formulation for a poroelasticity problem stemming from mixture theory

DOE PAGES

Costanzo, Francesco; Miller, Scott T.

2017-05-22

In this paper, a finite element formulation is developed for a poroelastic medium consisting of an incompressible hyperelastic skeleton saturated by an incompressible fluid. The governing equations stem from mixture theory and the application is motivated by the study of interstitial fluid flow in brain tissue. The formulation is based on the adoption of an arbitrary Lagrangian–Eulerian (ALE) perspective. We focus on a flow regime in which inertia forces are negligible. Finally, the stability and convergence of the formulation is discussed, and numerical results demonstrate agreement with the theory.

An arbitrary Lagrangian–Eulerian finite element formulation for a poroelasticity problem stemming from mixture theory

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

Costanzo, Francesco; Miller, Scott T.

In this paper, a finite element formulation is developed for a poroelastic medium consisting of an incompressible hyperelastic skeleton saturated by an incompressible fluid. The governing equations stem from mixture theory and the application is motivated by the study of interstitial fluid flow in brain tissue. The formulation is based on the adoption of an arbitrary Lagrangian–Eulerian (ALE) perspective. We focus on a flow regime in which inertia forces are negligible. Finally, the stability and convergence of the formulation is discussed, and numerical results demonstrate agreement with the theory.

Fluid Shifts

NASA Technical Reports Server (NTRS)

Stenger, M. B.; Hargens, A. R.; Dulchavsky, S. A.; Arbeille, P.; Danielson, R. W.; Ebert, D. J.; Garcia, K. M.; Johnston, S. L.; Laurie, S. S.; Lee, S. M. C.;

Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

PubMed

Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

2015-02-01

A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

N-glycan signatures identified in tumor interstitial fluid and serum of breast cancer patients: association with tumor biology and clinical outcome.

PubMed

Terkelsen, Thilde; Haakensen, Vilde D; Saldova, Radka; Gromov, Pavel; Hansen, Merete Kjaer; Stöckmann, Henning; Lingjaerde, Ole Christian; Børresen-Dale, Anne-Lise; Papaleo, Elena; Helland, Åslaug; Rudd, Pauline M; Gromova, Irina

2018-06-01

Particular N-glycan structures are known to be associated with breast malignancies by coordinating various regulatory events within the tumor and corresponding microenvironment, thus implying that N-glycan patterns may be used for cancer stratification and as predictive or prognostic biomarkers. However, the association between N-glycans secreted by breast tumor and corresponding clinical relevance remain to be elucidated. We profiled N-glycans by HILIC UPLC across a discovery dataset composed of tumor interstitial fluids (TIF, n = 85), paired normal interstitial fluids (NIF, n = 54) and serum samples (n = 28) followed by independent evaluation, with the ultimate goal of identifying tumor-related N-glycan patterns in blood of patients with breast cancer. The segregation of N-linked oligosaccharides revealed 33 compositions, which exhibited differential abundances between TIF and NIF. TIFs were depleted of bisecting N-glycans, which are known to play essential roles in tumor suppression. An increased level of simple high mannose N-glycans in TIF strongly correlated with the presence of tumor infiltrating lymphocytes within tumor. At the same time, a low level of highly complex N-glycans in TIF inversely correlated with the presence of infiltrating lymphocytes within tumor. Survival analysis showed that patients exhibiting increased TIF abundance of GP24 had better outcomes, whereas low levels of GP10, GP23, GP38, and coreF were associated with poor prognosis. Levels of GP1, GP8, GP9, GP14, GP23, GP28, GP37, GP38, and coreF were significantly correlated between TIF and paired serum samples. Cross-validation analysis using an independent serum dataset supported the observed correlation between TIF and serum, for five of nine N-glycan groups: GP8, GP9, GP14, GP23, and coreF. Collectively, our results imply that profiling of N-glycans from proximal breast tumor fluids is a promising strategy for determining tumor-derived glyco-signature(s) in the blood. N-glycans structures validated in our study may serve as novel biomarkers to improve the diagnostic and prognostic stratification of patients with breast cancer. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

An alternative explanation for the occurrence of short circuit current increases in the small intestine following challenge by bacterial enterotoxins.

PubMed

Lucas, M L

2013-10-01

Secretory diarrhoeal disease due to enterotoxins is thought to arise from the enhancement to pathologically high rates of normally occurring chloride ion and therefore fluid secretion from enterocytes. In support of this concept, many enterotoxins increase intestinal short-circuit current, regarded now as faithfully reflecting the increased chloride ion secretion. Contradicting this assumption, STa reduces absorption but does not cause secretion in vivo although short-circuit current is increased in vitro. There is therefore a mismatch between an assumed enterocyte mediated secretory event that should but does not cause net fluid secretion and an undoubtedly increased short-circuit current. It is proposed here that short-circuit current increases are not themselves secretory events but result from interrupted fluid absorption. A noteworthy feature of compounds that inhibit the increase in short-circuit current is that the majority are vasoactive, neuroactive or both. In general, vasodilator substances increase current. An alternative hypothesis for the origin of short-circuit current increases is that these result from reflex induction of electrogenic fluid absorption. This reflex enhances a compensatory response that is also present at a cellular level. An intestinal reflex is therefore proposed by which decreases in interstitial and intravascular volume or pressure within the intestine initiate an electrogenic fluid absorption mechanism that compensates for the loss of electrically neutral fluid absorption. This hypothesis would explain the apparently complex pharmacology of short-circuit current increases since many depressor substances have receptors in common with enterocytes and enteric nerves. The proposed alternative view of the origin of short-circuit current increases assumes that these do not represent chloride secretion from the enterocytes. This view may therefore aid the successful development of anti-diarrhoeal drugs to overcome a major cause of infant mortality worldwide, if short-circuit current data are being persistently misinterpreted. The putative but testable link between interstitial volume or pressure and fluid absorption also provides support for the alternative view of secretion; namely, that enhanced capillary and epithelial cell tight junctional permeability together with increased intracapillary pressure may cause secretion and not chloride exit from the enterocytes. Copyright © 2013. Published by Elsevier Ltd.

A role for MCP-1/CCR2 in interstitial lung disease in children

PubMed Central

Hartl, Dominik; Griese, Matthias; Nicolai, Thomas; Zissel, Gernot; Prell, Christine; Reinhardt, Dietrich; Schendel, Dolores J; Krauss-Etschmann, Susanne

2005-01-01

Background Interstitial lung diseases (ILD) are chronic inflammatory disorders leading to pulmonary fibrosis. Monocyte chemotactic protein 1 (MCP-1) promotes collagen synthesis and deletion of the MCP-1 receptor CCR2 protects from pulmonary fibrosis in ILD mouse models. We hypothesized that pulmonary MCP-1 and CCR2+ T cells accumulate in pediatric ILD and are related to disease severity. Methods Bronchoalveolar lavage fluid was obtained from 25 children with ILD and 10 healthy children. Levels of pulmonary MCP-1 and Th1/Th2-associated cytokines were quantified at the protein and the mRNA levels. Pulmonary CCR2+, CCR4+, CCR3+, CCR5+ and CXCR3+ T cells were quantified by flow-cytometry. Results CCR2+ T cells and MCP-1 levels were significantly elevated in children with ILD and correlated with forced vital capacity, total lung capacity and ILD disease severity scores. Children with lung fibrosis had significantly higher MCP-1 levels and CCR2+ T cells in bronchoalveolar lavage fluid compared to non-fibrotic children. Conclusion The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. PMID:16095529

Integrative models of vascular remodeling during tumor growth

PubMed Central

Rieger, Heiko; Welter, Michael

2015-01-01

Malignant solid tumors recruit the blood vessel network of the host tissue for nutrient supply, continuous growth, and gain of metastatic potential. Angiogenesis (the formation of new blood vessels), vessel cooption (the integration of existing blood vessels into the tumor vasculature), and vessel regression remodel the healthy vascular network into a tumor-specific vasculature that is in many respects different from the hierarchically organized arterio-venous blood vessel network of the host tissues. Integrative models based on detailed experimental data and physical laws implement in silico the complex interplay of molecular pathways, cell proliferation, migration, and death, tissue microenvironment, mechanical and hydrodynamic forces, and the fine structure of the host tissue vasculature. With the help of computer simulations high-precision information about blood flow patterns, interstitial fluid flow, drug distribution, oxygen and nutrient distribution can be obtained and a plethora of therapeutic protocols can be tested before clinical trials. In this review, we give an overview over the current status of integrative models describing tumor growth, vascular remodeling, blood and interstitial fluid flow, drug delivery, and concomitant transformations of the microenvironment. © 2015 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. PMID:25808551

Photo-acoustic sensor based on an inexpensive piezoelectric film transducer and an amplitude-stabilized single-mode external cavity diode laser for in vitro measurements of glucose concentration

NASA Astrophysics Data System (ADS)

Bayrakli, Ismail; Erdogan, Yasar Kemal

2018-06-01

The present paper focuses on development of a compact photo-acoustic sensor using inexpensive components for glucose analysis. An amplitude-stabilized wavelength-tunable single-mode external cavity diode laser operating around 1050 nm was realized and characterized for the use of laser beam as an excitation light source. In the established setup, a fine tuning range of 9 GHz was achieved. The glucose solution was obtained by diluting D-glucose in sterile water. The acoustic signal generated by the optical excitation was detected via a chip piezoelectric film transducer. A detection limit of 50 mM (900 mg/dl) was achieved. The device may be of great interest for its applications in medicine and health monitoring. The sensor is promising for non-invasive in vivo glucose measurements from interstitial fluid.

Fluid extravasation during cardiopulmonary bypass in piglets--effects of hypothermia and different cooling protocols.

PubMed

Farstad, M; Heltne, J K; Rynning, S E; Lund, T; Mongstad, A; Eliassen, F; Husby, P

2003-04-01

Hypothermic cardiopulmonary bypass (CPB) is associated with capillary fluid leak and edema generation which may be secondary to hemodilution, inflammation and hypothermia. We evaluated how hypothermia and different cooling strategies influenced the fluid extravasation rate during CPB. Fourteen piglets were given 60 min normothermic CPB, followed by randomization to two groups: 1: rapid cooling (RC-group) ( approximately 15 min to 28 degrees C); 2: slow cooling (SC-group) ( approximately 60 min to 28 degrees C). Ringer's solution was used as CPB prime and for fluid supplementation. Fluid input/losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum-proteins and total tissue water (TTW) were measured and fluid extravasation rates calculated. Start of normothermic CPB resulted in a 25% hemodilution. During the first 5-10 min the fluid level of the reservoir fell markedly due to an intravascular volume loss necessitating fluid supplementation. Thereafter a steady state was reached with a constant fluid need of 0.14 +/- 0.04 ml kg-1 min-1. After start of cooling the fluid needs increased in the following 30 min to 0.91 +/- 0.11 ml kg-1 min-1 in the RC group (P < 0.001) and 0.63 +/- 0.10 ml kg-1 min-1 in the SC-group (P < 0.001) with no statistical between-group differences. Fluid extravasation rates after start of hypothermic CPB increased from 0.20 +/- 0.08 ml kg-1 min-1 to 0.71 +/- 0.13 (P < 0.01) and 0.62 +/- 0.13 ml kg-1 min-1 (P < 0.05) in the RC- and SC-groups, respectively, without any changes in degree of hemodilution. TTW increased in most tissues, whereas the intravascular albumin and protein masses remained constant with no between group differences. Hypothermia increased fluid extravasation during CPB independent of cooling strategy. Intravascular albumin and protein masses remained constant. Since inflammatory fluid leakage usually results in protein rich exudates, our data with no net protein leakage may indicate that mechanisms other than inflammation could contribute to fluid extravasation during hypothermic CPB.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer.

PubMed

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-09-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib.

Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

PubMed Central

Matsumoto, Yoshiya; Kawaguchi, Tomoya; Yamamoto, Norio; Sawa, Kenji; Yoshimoto, Naoki; Suzumura, Tomohiro; Watanabe, Tetsuya; Mitsuoka, Shigeki; Asai, Kazuhisa; Kimura, Tatsuo; Yoshimura, Naruo; Kuwae, Yuko; Hirata, Kazuto

2017-01-01

A 75-year-old man with stage IV lung adenocarcinoma was treated with osimertinib due to disease progression despite having been administered erlotinib. Both an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790M mutation on exon 20 were detected in a specimen from a recurrent primary tumor. Five weeks after osimertinib initiation, he developed general fatigue and dyspnea. Chest computed tomography scan revealed diffuse ground glass opacities and consolidation on both lungs. An analysis of the bronchoalveolar lavage fluid revealed marked lymphocytosis, and a transbronchial lung biopsy specimen showed a thickened interstitium with fibrosis and prominent lymphocytic infiltration. We diagnosed the patient to have interstitial lung disease induced by osimertinib. PMID:28794368

Cancer Cell Glycocalyx Mediates Mechanostransduction and Flow-Regulated Invasion

PubMed Central

Qazi, Henry; Palomino, Rocio; Shi, Zhong-Dong; Munn, Lance L.; Tarbell, John M.

2014-01-01

Mammalian cells are covered by a surface proteoglycan (glycocalyx) layer, and it is known that blood vessel-lining endothelial cells use the glycocalyx to sense and transduce the shearing forces of blood flow into intracellular signals. Tumor cells in vivo are exposed to forces from interstitial fluid flow that may affect metastatic potential but are not reproduced by most in vitro cell motility assays. We hypothesized that glycocalyx-mediated mechanotransduction of interstitial flow shear stress is an un-recognized factor that can significantly enhance metastatic cell motility and play a role in augmentation of invasion. Involvement of MMP levels, cell adhesion molecules (CD44, α3 integrin), and glycocalyx components (heparan sulfate and hyaluronan) were investigated in a cell/collagen gel suspension model designed to mimic the interstitial flow microenvironment. Physiologic levels of flow upregulated MMP levels and enhanced the motility of metastatic cells. Blocking the flow-enhanced expression of MMP actvity or adhesion molecules (CD44 and integrins) resulted in blocking the flow-enhanced migratory activity. The presence of a glycocalyx-like layer was verified around tumor cells, and the degradation of this layer by hyaluronidase and heparinase blocked the flow-regulated invasion. This study shows for the first time that interstitial flow enhancement of metastatic cell motility can be mediated by the cell surface glycocalyx – a potential target for therapeutics. PMID:24077103

Acute Exacerbation in Interstitial Lung Disease

PubMed Central

Leuschner, Gabriela; Behr, Jürgen

2017-01-01

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947

A Feasibility Study to Determine Whether Clinical Contrast Enhanced Magnetic Resonance Imaging can Detect Increased Bladder Permeability in Patients with Interstitial Cystitis.

PubMed

Towner, Rheal A; Wisniewski, Amy B; Wu, Dee H; Van Gordon, Samuel B; Smith, Nataliya; North, Justin C; McElhaney, Rayburt; Aston, Christopher E; Shobeiri, S Abbas; Kropp, Bradley P; Greenwood-Van Meerveld, Beverley; Hurst, Robert E

2016-03-01

Interstitial cystitis/bladder pain syndrome is a bladder pain disorder associated with voiding symptomatology and other systemic chronic pain disorders. Currently diagnosing interstitial cystitis/bladder pain syndrome is complicated as patients present with a wide range of symptoms, physical examination findings and clinical test responses. One hypothesis is that interstitial cystitis symptoms arise from increased bladder permeability to urine solutes. This study establishes the feasibility of using contrast enhanced magnetic resonance imaging to quantify bladder permeability in patients with interstitial cystitis. Permeability alterations in bladder urothelium were assessed by intravesical administration of the magnetic resonance imaging contrast agent Gd-DTPA (Gd-diethylenetriaminepentaacetic acid) in a small cohort of patients. Magnetic resonance imaging signal intensity in patient and control bladders was compared regionally and for entire bladders. Quantitative assessment of magnetic resonance imaging signal intensity indicated a significant increase in signal intensity in anterior bladder regions compared to posterior regions in patients with interstitial cystitis (p <0.01) and significant increases in signal intensity in anterior bladder regions (p <0.001). Kurtosis (shape of probability distribution) and skewness (measure of probability distribution asymmetry) were associated with contrast enhancement in total bladders in patients with interstitial cystitis vs controls (p <0.05). Regarding symptomatology interstitial cystitis cases differed significantly from controls on the SF-36®, PUF (Pelvic Pain and Urgency/Frequency) and ICPI (Interstitial Cystitis Problem Index) questionnaires with no overlap in the score range in each group. ICSI (Interstitial Cystitis Symptom Index) differed significantly but with a slight overlap in the range of scores. Data suggest that contrast enhanced magnetic resonance imaging provides an objective, quantifiable measurement of bladder permeability that could be used to stratify bladder pain patients and monitor therapy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Automatic vision system for analysis of microscopic behavior of flow and transport in porous media

NASA Astrophysics Data System (ADS)

Rashidi, Mehdi; Dehmeshki, Jamshid; Dickenson, Eric; Daemi, M. Farhang

1997-10-01

This paper describes the development of a novel automated and efficient vision system to obtain velocity and concentration measurement within a porous medium. An aqueous fluid lace with a fluorescent dye to microspheres flows through a transparent, refractive-index-matched column packed with transparent crystals. For illumination purposes, a planar sheet of laser passes through the column as a CCD camera records all the laser illuminated planes. Detailed microscopic velocity and concentration fields have been computed within a 3D volume of the column. For measuring velocities, while the aqueous fluid, laced with fluorescent microspheres, flows through the transparent medium, a CCD camera records the motions of the fluorescing particles by a video cassette recorder. The recorded images are acquired automatically frame by frame and transferred to the computer for processing, by using a frame grabber an written relevant algorithms through an RS-232 interface. Since the grabbed image is poor in this stage, some preprocessings are used to enhance particles within images. Finally, these enhanced particles are monitored to calculate velocity vectors in the plane of the beam. For concentration measurements, while the aqueous fluid, laced with a fluorescent organic dye, flows through the transparent medium, a CCD camera sweeps back and forth across the column and records concentration slices on the planes illuminated by the laser beam traveling simultaneously with the camera. Subsequently, these recorded images are transferred to the computer for processing in similar fashion to the velocity measurement. In order to have a fully automatic vision system, several detailed image processing techniques are developed to match exact images that have different intensities values but the same topological characteristics. This results in normalized interstitial chemical concentrations as a function of time within the porous column.

Bed-rest studies - Fluid and electrolyte responses

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.

1983-01-01

Confinement in the horizontal position for 2 to 3 weeks results in a chronic decrease in plasma volume, increased interstitial fluid volume, and unchanged or slightly increased extracellular fluid volume. Concentrations of blood electrolytes, glucose, and nitrogenous constituents remain within normal limits of variability when maintenance levels of isometric or isotonic exercise are performed for 1 hr/day. Hematocrit and plasma osmolality can be elevated significantly throughout bed rest (BR). Significant diuresis occurs on the first day, and increases in urine Na and Ca continue throughout BR, although voluntary fluid intake is unchanged. Urine Na and K are evaluated during the second week of BR in spite of stabilization of PV and extracellular volume. The initial diuresis probably arises from extracellular fluid while subsequent urine loss above control levels must come from the intracellular fluid. Preservation of the extracellular volume takes precedance over maintenance of the intracellular fluid volume. The functioning of a natriuretic factor (hormone) to account for the continued increased loss of Na in the urine is suggested. Previously announced in STAR as N83-24160

The pattern of early lung parenchymal and air space injury following acute blood loss.

PubMed

Younger, J G; Taqi, A S; Jost, P F; Till, G O; Johnson, K J; Stern, S A; Hirschl, R B

1998-07-01

Acute lung injury is a frequent clinical occurrence following blood loss and trauma. The nature of this injury remains poorly understood. To examine the relative parenchymal and intra-alveolar distribution of inflammation in a rat model of hemorrhage and resuscitation. Rats were anesthetized and subjected to hemorrhage followed by resuscitation with shed blood and saline. Myeloperoxidase activity of lung homogenates and cytology of bronchoalveolar lavage fluid were used to measure total lung and intra-alveolar neutrophil invasion. Extravasation of i.v.-administered [125I]-albumin was used to determine total lung and alveolar permeability. Permeability results were analyzed using their base-10 logarithmic transformations. 86 animals were studied. Whole-lung myeloperoxidase activity was increased (control = 0.34 +/- 0.16 units, injured = 0.84 +/- 0.43 units, p < 0.01), while there was no difference in intra-alveolar leukocyte counts (injured = 1.85 +/- 1.30 x 10(5)/mL, control = 2.44 +/- 1.75 x 10(5)/mL, p = 0.40), suggesting that the cellular component of the injury was more severe in the intravascular and interstitial spaces. There was a strong trend toward increased permeability in the interstitial compartment, and a significant increase in permeability in the intra-alveolar compartment (whole-lung permeability: control = -0.27 +/- 0.19 units, injured = 0.10 +/- 0.55 units, p = 0.06; alveolar permeability: control = -2.00 +/- 0.47 units, injured = -1.32 +/- 0.49 units, p < 0.01), suggesting that the loss of integrity to macromolecules was not limited to the interstitium. Hemorrhage and resuscitation resulted in an acute lung injury characterized by extravasation of intravascular protein into both the interstitium and the intra-alveolar space. Neutrophil invasion of the lung was demonstrable only in the interstitial compartment.

Understanding the role of the perivascular space in cerebral small vessel disease.

PubMed

Brown, Rosalind; Benveniste, Helene; Black, Sandra E; Charpak, Serge; Dichgans, Martin; Joutel, Anne; Nedergaard, Maiken; Smith, Kenneth J; Zlokovic, Berislav V; Wardlaw, Joanna M

2018-05-02

Small vessel diseases are a group of disorders that result from pathological alteration of the small blood vessels in the brain, including the small arteries, capillaries and veins. Of the 35-36 million people that are estimated to suffer from dementia worldwide, up to 65% have an SVD component. Furthermore, SVD causes 20-25% of strokes, worsens outcome after stroke and is a leading cause of disability, cognitive impairment and poor mobility. Yet the underlying cause(s) of SVD are not fully understood.Magnetic resonance imaging (MRI) has confirmed enlarged perivascular spaces (PVS) as a hallmark feature of SVD. In healthy tissue, these spaces are proposed to form part of a complex brain fluid drainage system which supports interstitial fluid exchange and may also facilitate clearance of waste products from the brain. The pathophysiological signature of PVS, and what this infers about their function and interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development in the brain has not been established. Here we discuss the potential of enlarged PVS to be a unique biomarker for SVD and related brain disorders with a vascular component. We propose that widening of PVS suggests presence of peri-vascular cell debris and other waste products that forms part of a vicious cycle involving impaired cerebrovascular reactivity (CVR), blood-brain barrier (BBB) dysfunction, perivascular inflammation and ultimately impaired clearance of waste proteins from the interstitial fluid (ISF) space, leading to accumulation of toxins, hypoxia and tissue damage.Here, we outline current knowledge, questions and hypotheses regarding understanding the brain fluid dynamics underpinning dementia and stroke through the common denominator of SVD.

Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review).

PubMed

Agnati, Luigi F; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

2017-03-01

In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico‑physical parameters, oscillatory rhythms within their proper set‑ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio‑pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.

Homeostasis and the concept of 'interstitial fluids hierarchy': Relevance of cerebrospinal fluid sodium concentrations and brain temperature control (Review)

PubMed Central

Agnati, Luigi F.; Marcoli, Manuela; Leo, Giuseppina; Maura, Guido; Guidolin, Diego

2017-01-01

In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. However, the new concept of a hierarchic role of ISF of the various organs is introduced. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Furthermore, the evolutionary links between brain and kidney and their synergistic role in H2O/Na balance and brain temperature control are discussed. Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis. PMID:28204813

Mechanisms to explain the reverse perivascular transport of solutes out of the brain.

PubMed

Schley, D; Carare-Nnadi, R; Please, C P; Perry, V H; Weller, R O

2006-02-21

Experimental studies and observations in the human brain indicate that interstitial fluid and solutes, such as amyloid-beta (Abeta), are eliminated from grey matter of the brain along pericapillary and periarterial pathways. It is unclear, however, what constitutes the motive force for such transport within blood vessel walls, which is in the opposite direction to blood flow. In this paper the potential for global pressure differences to achieve such transport are considered. A mathematical model is constructed in order to test the hypothesis that perivascular drainage of interstitial fluid and solutes out of brain tissue is driven by pulsations of the blood vessel walls. Here it is assumed that drainage occurs through a thin layer between astrocytes and endothelial cells or between smooth muscle cells. The model suggests that, during each pulse cycle, there are periods when fluid and solutes are driven along perivascular spaces in the reverse direction to the flow of blood. It is shown that successful drainage may depend upon some attachment of solutes to the lining of the perivascular space, in order to produce a valve-like effect, although an alternative without this requirement is also postulated. Reduction in pulse amplitude, as in ageing cerebral vessels, would prolong the attachment time, encourage precipitation of Abeta peptides in vessel walls, and impair elimination of Abeta from the brain. These factors may play a role in the pathogenesis of cerebral amyloid angiopathy and in the accumulation of Abeta in the brain in Alzheimer's disease.

Influence of gravity for optimal head positions in the treatment of head injury patients.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2011-10-01

Brain edema is a major neurological complication of traumatic brain injury (TBI), commonly including a pathologically increased intracranial pressure (ICP) associated with poor outcome. In this study, gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue and the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a finite element (FE) model. A detailed FE model including the meninges, brain tissue and a fully connected cerebrospinal fluid (CSF) system was used in this study. Brain tissue was modelled as a poroelastic material consisting of an elastic solid skeleton composed of neurons and neuroglia, permeated by interstitial fluid. The effect of head positions (supine and prone position) due to gravity was investigated for a localized brain edema at the posterior part of the brain. The water content increment at the edema zone remained nearly identical for both positions. However, the interstitial fluid pressure (IFP) inside the edema zone decreased around 15% by having the head in a prone position compared with a supine position. The decrease of IFP inside the edema zone by changing patient position from supine to prone has the potential to alleviate the damage to central nervous system nerves. These observations indicate that considering the patient's head position during intensive care and at rehabilitation might be of importance to the treatment of edematous regions in TBI patients.

Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

PubMed

Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

2013-01-01

There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Microfluidic Enhancement of Intramedullary Pressure Increases Interstitial Fluid Flow and Inhibits Bone Loss in Hindlimb Suspended Mice

PubMed Central

Kwon, Ronald Y; Meays, Diana R; Tang, W Joyce; Frangos, John A

2010-01-01

Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process. © 2010 American Society for Bone and Mineral Research. PMID:20200992

Lymphatic System Flows

NASA Astrophysics Data System (ADS)

Moore, James E., Jr.; Bertram, Christopher D.

2018-01-01

The supply of oxygen and nutrients to tissues is performed by the blood system and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH2O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls. Passive vessel squeezing causes further pumping. The dynamics of lymphatic pumping have been investigated experimentally and mathematically, revealing complex behaviors that indicate that the system performance is robust against minor perturbations in pressure and flow. More serious disruptions can lead to incurable swelling of tissues called lymphedema.

Fluids and sepsis: changing the paradigm of fluid therapy: a case report.

PubMed

Hariyanto, Hori; Yahya, Corry Quando; Widiastuti, Monika; Wibowo, Primartanto; Tampubolon, Oloan Eduard

2017-02-04

Over the past 16 years, sepsis management has been guided by large-volume fluid administration to achieve certain hemodynamic optimization as advocated in the Rivers protocol. However, the safety of such practice has been questioned because large-volume fluid administration is associated with fluid overload and carries the worst outcome in patients with sepsis. Researchers in multiple studies have declared that using less fluid leads to increased survival, but they did not describe how to administer fluids in a timely and appropriate manner. An 86-year-old previously healthy Sundanese man was admitted to the intensive care unit at our institution with septic shock, acute kidney injury, and respiratory distress. Standard care was implemented during his initial care in the high-care unit; nevertheless, his condition worsened, and he was transferred to the intensive care unit. We describe the timing of fluid administration and elaborate on the amount of fluids needed using a conservative fluid regimen in a continuum of resuscitated sepsis. Because fluid depletion in septic shock is caused by capillary leak and pathologic vasoplegia, continuation of fluid administration will drive intravascular fluid into the interstitial space, thereby producing marked tissue edema and disrupting vital oxygenation. Thus, fluids have the power to heal or kill. Therefore, management of patients with sepsis should entail early vasopressors with adequate fluid resuscitation followed by a conservative fluid regimen.

Interstitial space and collagen alterations of the developing rat diaphragm

NASA Technical Reports Server (NTRS)

Gosselin, L. E.; Martinez, D. A.; Vailas, A. C.; Sieck, G. C.

1993-01-01

The effect of growth on the relative interstitial space [%total cross-sectional area (CSA)] and collagen content of the rat diaphragm muscle was examined at postnatal ages of 0, 7, 14, and 21 days as well as in adult males. The proportion of interstitial space relative to total muscle CSA was determined by computerized image analysis of lectin-stained cross sections of diaphragm muscle. To assess collagen content and extent of collagen maturation (i.e., cross-linking), high-pressure liquid chromatography analysis was used to measure hydroxyproline concentration and the nonreducible collagen cross-link hydroxylysylpyridinoline (HP), respectively. At birth, interstitial space accounted for approximately 47% of total diaphragm muscle CSA. During postnatal growth, the relative contribution of interstitial space decreased such that by adulthood the interstitial space accounted for approximately 18% of total muscle CSA. The change in relative interstitial space occurred without a concomitant change in hydroxyproline concentration. However, the concentration of HP markedly increased with age such that the adult diaphragm contained approximately 17 times more HP than at birth. These results indicate that during development the relative CSA occupied by interstitial space decreases as muscle fiber size increases. However, the reduction in relative interstitial space is not associated with a change in collagen concentration. Thus collagen density in the interstitial space may increase with age. It is possible that the observed changes in relative interstitial space and collagen influence the passive length-force properties of the diaphragm.

Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid.

PubMed

D'Auria, L; Pimpinelli, F; Ferraro, C; D'Ambrogio, G; Giacalone, B; Bellocci, M; Ameglio, F

1998-01-01

Bullous pemphigoid (BP) blisters contain several molecules, some of which spread into the blisters from the interstitial fluid, while others are produced locally and migrate into the circulation. The calculation of the ratios between blister/serum concentrations may help to distinguish between these two types of molecules. The rules regulating the diffusion of the molecules have been described only in suction blisters, where the theoretical molecular weight (MW) represents one of the principal influencing factors. The aim of the present study was to analyse the relationship between theoretical MWs and the ratios of concentrations of several molecules evaluated both in sera and in blister fluids. Eight cytokines (interleukin-2, interleukin-3, interleukin-4, interleukin-5, interleukin-10, tumor necrosis factor-alpha, oncostatin-M and vascular endothelial growth factor), two acute phase reactants (alpha-1 acid glycoprotein, haptoglobin), albumin, one soluble membrane molecule with adhesion functions (sICAM-1) and the eosinophil cathionic protein (ECP) were measured in samples from 15 patients affected with BP by means of commercially available tests. The data suggest that the MW may influence the rate of diffusion throughout the blister, both in input and output directions, despite the discontinuity observed at the basement membrane level on the BP blister floor.

Spatially-Resolved Hydraulic Conductivity Estimation Via Poroelastic Magnetic Resonance Elastography

PubMed Central

McGarry, Matthew; Weaver, John B.; Paulsen, Keith D.

2015-01-01

Poroelastic magnetic resonance elastography is an imaging technique that could recover mechanical and hydrodynamical material properties of in vivo tissue. To date, mechanical properties have been estimated while hydrodynamical parameters have been assumed homogeneous with literature-based values. Estimating spatially-varying hydraulic conductivity would likely improve model accuracy and provide new image information related to a tissue’s interstitial fluid compartment. A poroelastic model was reformulated to recover hydraulic conductivity with more appropriate fluid-flow boundary conditions. Simulated and physical experiments were conducted to evaluate the accuracy and stability of the inversion algorithm. Simulations were accurate (property errors were < 2%) even in the presence of Gaussian measurement noise up to 3%. The reformulated model significantly decreased variation in the shear modulus estimate (p≪0.001) and eliminated the homogeneity assumption and the need to assign hydraulic conductivity values from literature. Material property contrast was recovered experimentally in three different tofu phantoms and the accuracy was improved through soft-prior regularization. A frequency-dependence in hydraulic conductivity contrast was observed suggesting that fluid-solid interactions may be more prominent at low frequency. In vivo recovery of both structural and hydrodynamical characteristics of tissue could improve detection and diagnosis of neurological disorders such as hydrocephalus and brain tumors. PMID:24771571

Early Archean serpentine mud volcanoes at Isua, Greenland, as a niche for early life

PubMed Central

Pons, Marie-Laure; Quitté, Ghylaine; Fujii, Toshiyuki; Rosing, Minik T.; Reynard, Bruno; Moynier, Frederic; Douchet, Chantal; Albarède, Francis

2011-01-01

The Isua Supracrustal Belt, Greenland, of Early Archean age (3.81–3.70 Ga) represents the oldest crustal segment on Earth. Its complex lithology comprises an ophiolite-like unit and volcanic rocks reminiscent of boninites, which tie Isua supracrustals to an island arc environment. We here present zinc (Zn) isotope compositions measured on serpentinites and other rocks from the Isua supracrustal sequence and on serpentinites from modern ophiolites, midocean ridges, and the Mariana forearc. In stark contrast to modern midocean ridge and ophiolite serpentinites, Zn in Isua and Mariana serpentinites is markedly depleted in heavy isotopes with respect to the igneous average. Based on recent results of Zn isotope fractionation between coexisting species in solution, the Isua serpentinites were permeated by carbonate-rich, high-pH hydrothermal solutions at medium temperature (100–300 °C). Zinc isotopes therefore stand out as a pH meter for fossil hydrothermal solutions. The geochemical features of the Isua fluids resemble the interstitial fluids sampled in the mud volcano serpentinites of the Mariana forearc. The reduced character and the high pH inferred for these fluids make Archean serpentine mud volcanoes a particularly favorable setting for the early stabilization of amino acids. PMID:22006301

a Study of Oxygen Precipitation in Heavily Doped Silicon.

NASA Astrophysics Data System (ADS)

Graupner, Robert Kurt

Gettering of impurities with oxygen precipitates is widely used during the fabrication of semiconductors to improve the performance and yield of the devices. Since the effectiveness of the gettering process is largely dependent on the initial interstitial oxygen concentration, accurate measurements of this parameter are of considerable importance. Measurements of interstitial oxygen following thermal cycles are required for development of semiconductor fabrication processes and for research into the mechanisms of oxygen precipitate nucleation and growth. Efforts by industrial associations have led to the development of standard procedures for the measurement of interstitial oxygen in wafers. However practical oxygen measurements often do not satisfy the requirements of such standard procedures. An additional difficulty arises when the silicon wafer has a low resitivity (high dopant concentration). In such cases the infrared light used for the measurement is severely attenuated by the electrons of holes introduced by the dopant. Since such wafers are the substrates used for the production of widely used epitaxial wafers, this measurement problem is economically important. Alternative methods such as Secondary Ion Mass Spectroscopy or Gas Fusion Analysis have been developed to measure oxygen in these cases. However, neither of these methods is capable of distinguishing interstitial oxygen from precipitated oxygen as required for precipitation studies. In addition to the commercial interest in heavily doped silicon substrates, they are also of interest for research into the role of point defects in nucleation and precipitation processes. Despite considerable research effort, there is still disagreement concerning the type of point defect and its role in semiconductor processes. Studies of changes in the interstitial oxygen concentration of heavily doped and lightly doped silicon wafers could help clarify the role of point defects in oxygen nucleation and precipitation processes. This could lead to more effective control and use of oxygen precipitation for gettering. One of the principal purposes of this thesis is the extension of the infrared interstitial oxygen measurement technique to situations outside the measurement capacities of the standard technique. These situations include silicon slices exhibiting interfering precipitate absorption bands and heavily doped n-type silicon wafers. A new method is presented for correcting for the effect of multiple reflections in silicon wafers with optically rough surfaces. The technique for the measurement of interstitial oxygen in heavily doped n-type wafers is then used to perform a comparative study of oxygen precipitation in heavily antimony doped (.035 ohm-cm) silicon and lightly doped p-type silicon. A model is presented to quantitatively explain the observed suppression of defect formation in heavily doped n-type wafers.

An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice

PubMed Central

Sheline, Yvette I.; West, Tim; Yarasheski, Kevin; Swarm, Robert; Jasielec, Mateusz S.; Fisher, Jonathan R.; Ficker, Whitney D.; Yan, Ping; Xiong, Chengjie; Frederiksen, Christine; Grzelak, Monica V.; Chott, Robert; Bateman, Randall J.; Morris, John C.; Mintun, Mark A.; Lee, Jin-Moo; Cirrito, John R.

2014-01-01

Serotonin signaling suppresses generation of amyloid-β (Aβ) in vitro and in animal models of Alzheimer’s disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor (SSRI), decreased Aβ in brain interstitial fluid (ISF) in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of pre-existing plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable-isotope labeling kinetics (SILK), with CSF sampling during acute dosing of citalopram. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials. PMID:24828079

Fluid Shifts

NASA Technical Reports Server (NTRS)

Stenger, Michael; Hargens, A.; Dulchavsky, S.; Ebert, D.; Lee, S.; Sargsyan, A.; Martin, D.; Lui, J.; Macias, B.; Arbeille, P.;

Fluid Shifts

NASA Technical Reports Server (NTRS)

Stenger, M.; Hargens, A.; Dulchavsky, S.; Ebert, D.; Lee, S.; Lauriie, S.; Garcia, K.; Sargsyan, A.; Martin, D.; Ribeiro, L.;

Comparison of Interstitial Fluid pH, PCO2, PO2 with Venous Blood Values During Repetitive Handgrip Exercise

NASA Technical Reports Server (NTRS)

Hagan, Ronald Donald; Soller, Babs R.; Shear, Michael; Walz, Matthias; Landry, Michelle; Heard, Stephen

2006-01-01

We evaluated the use of a small, fiber optic sensor to measure pH, PCO2 and PO2 from forearm muscle interstitial fluid (IF) during handgrip dynamometry. PURPOSE: Compare pH, PCO2 and PO2 values obtained from venous blood with those from the IF of the flexor digitorum superficialis (FDS) during three levels of exercise intensity. METHODS: Six subjects (5M/1F), average age 29+/-5 yrs, participated in the study. A venous catheter was placed in the retrograde direction in the antecubital space and a fiber optic sensor (Paratrend, Diametrics Medical, Inc.) was placed through a 22 G catheter into the FDS muscle under ultrasound guidance. After a 45 min rest period, subjects performed three 5-min bouts of repetitive handgrip exercise (2s contraction/1 s relaxation) at attempted levels of 15%, 30% and 45% of maximal voluntary contraction. The order of the exercise bouts was random with the second and third bouts started after blood lactate had returned to baseline. Venous blood was sampled every minute during exercise and analyzed with an I-Stat CG-4+ cartridge, while IF fiber optic sensor measurements were obtained every 2 s. Change from pre-exercise baseline to end of exercise was computed for pH, PCO2 and PO2. Blood and IF values were compared with a paired t-test. RESULTS: Baseline values for pH, PCO2 and PO2 were 7.37+/-0.02, 46+/-4 mm Hg, and 36+/-6 mm Hg respectively in blood and 7.39+/-0.02, 44+/-6 mm Hg, and 35+/-14 mm Hg in IF. Average changes over all exercise levels are noted in the Table below. For each parameter the exercise-induced change was at least twice as great in IF as in blood. In blood and IF, pH and PCO2 increases were directly related to exercise intensity. Change in venous PO2 was unrelated to exercise intensity, while IF PO2 decreased with increases in exercise intensity. CONCLUSIONS: Measurement of IF pH, PCO2 and PO2 is more sensitive to exercise intensity than measurement of the same parameters in venous blood and provides continuous assessment during and after exercise.

[The glymphatic system: concept, function and research progresses].

PubMed

Wang, Lin-Hui; Wang, Zi-Lan; Chen, Wen-Yue; Chen, Ming-Jia; Xu, Guang-Yin

2018-02-25

The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

Borehole geophysics applied to ground-water investigations

USGS Publications Warehouse

Keys, W.S.

1990-01-01

The purpose of this manual is to provide hydrologists, geologists, and others who have the necessary background in hydrogeology with the basic information needed to apply the most useful borehole-geophysical-logging techniques to the solution of problems in ground-water hydrology. Geophysical logs can provide information on the construction of wells and on the character of the rocks and fluids penetrated by those wells, as well as on changes in the character of these factors over time. The response of well logs is caused by petrophysical factors, by the quality, temperature, and pressure of interstitial fluids, and by ground-water flow. Qualitative and quantitative analysis of analog records and computer analysis of digitized logs are used to derive geohydrologic information. This information can then be extrapolated vertically within a well and laterally to other wells using logs. The physical principles by which the mechanical and electronic components of a logging system measure properties of rocks, fluids, and wells, as well as the principles of measurement, must be understood if geophysical logs are to be interpreted correctly. Plating a logging operation involves selecting the equipment and the logs most likely to provide the needed information. Information on well construction and geohydrology is needed to guide this selection. Quality control of logs is an important responsibility of both the equipment operator and the log analyst and requires both calibration and well-site standardization of equipment. Logging techniques that are widely used in ground-water hydrology or that have significant potential for application to this field include spontaneous potential, resistance, resistivity, gamma, gamma spectrometry, gamma-gamma, neutron, acoustic velocity, acoustic televiewer, caliper, and fluid temperature, conductivity, and flow. The following topics are discussed for each of these techniques: principles and instrumentation, calibration and standardization, volume of investigation, extraneous effects, and interpretation and applications.

Borehole geophysics applied to ground-water investigations

USGS Publications Warehouse

Keys, W.S.

1988-01-01

The purpose of this manual is to provide hydrologists, geologists, and others who have the necessary training with the basic information needed to apply the most useful borehole-geophysical-logging techniques to the solution of problems in ground-water hydrology. Geophysical logs can provide information on the construction of wells and on the character of the rocks and fluids penetrated by those wells, in addition to changes in the character of these factors with time. The response of well logs is caused by: petrophysical factors; the quality; temperature, and pressure of interstitial fluids; and ground-water flow. Qualitative and quantitative analysis of the analog records and computer analysis of digitized logs are used to derive geohydrologic information. This information can then be extrapolated vertically within a well and laterally to other wells using logs.The physical principles by which the mechanical and electronic components of a logging system measure properties of rocks, fluids and wells, and the principles of measurement need to be understood to correctly interpret geophysical logs. Planning the logging operation involves selecting the equipment and the logs most likely to provide the needed information. Information on well construction and geohydrology are needed to guide this selection. Quality control of logs is an important responsibility of both the equipment operator and log analyst and requires both calibration and well-site standardization of equipment.Logging techniques that are widely used in ground-water hydrology or that have significant potential for application to this field include: spontaneous potential, resistance, resistivity, gamma, gamma spectrometry, gamma-gamma, neutron, acoustic velocity, acoustic televiewer, caliper, and fluid temperature, conductivity, and flow. The following topics are discussed for each of these techniques: principles and instrumentation, calibration and standardization, volume of investigation, extraneous effects, and interpretation and applications.

Atomic diffusion in strain fields near solutes

NASA Astrophysics Data System (ADS)

Shropshire, Steven L.; Collins, Gary S.

1993-03-01

Annihilation reactions between mobile self-interstitial defects and complexes of vacancies with111In probe solutes in Au were studied. Measurements were made using the technique of perturbed angular correlations of gamma rays (PAC). Au samples were doped with complexes and plastically deformed at a low temperature to generate fluxes of self-interstitials. Changes in the concentrations of monovacancy (1V) to tetravacancy (4V) complexes induced by annihilation reactions were measured. These are now analysed using a system of coupled first-order equations in order to obtain interstitial annihilation cross sections of the complexes and the fractional amounts of different interstitial clusters in the flux. Relative cross sections obtained for Au are 1.0(1), 3.3(3), 1.2(2) and 7.5(2.5), respectively, for 1V to 4V complexes. The large increase in the cross sections with vacancy number is attributed to a progressive relaxation of the dilatational strain surrounding the oversized In solute as more vacancies are trapped. Also obtained from the analysis are values 0.34(5), 0.66(7), 0.0(1) and 0.0(2), respectively, for the fractions of mobile 1I to 4I clusters in deformed Au, indicating that di-interstitials are produced more readily than mono-interstitials during plastic deformation.

MR-guided transcranial focused ultrasound safely enhances interstitial dispersion of large polymeric nanoparticles in the living brain

PubMed Central

Mohammadabadi, Ali; Nguyen, Ben A.; Guo, Sijia; Winkles, Jeffrey A.; Kim, Anthony J.; Gullapalli, Rao; Keller, Asaf; Frenkel, Victor

2018-01-01

Generating spatially controlled, non-destructive changes in the interstitial spaces of the brain has a host of potential clinical applications, including enhancing the delivery of therapeutics, modulating biological features within the tissue microenvironment, altering fluid and pressure dynamics, and increasing the clearance of toxins, such as plaques found in Alzheimer’s disease. Recently we demonstrated that ultrasound can non-destructively enlarge the interstitial spaces of the brain ex vivo. The goal of the current study was to determine whether these effects could be reproduced in the living brain using non-invasive, transcranial MRI-guided focused ultrasound (MRgFUS). The left striatum of healthy rats was treated using MRgFUS. Computer simulations facilitated treatment planning, and targeting was validated using MRI acoustic radiation force impulse imaging. Following MRgFUS treatments, Evans blue dye or nanoparticle probes were infused to assess changes in the interstitial space. In MRgFUS-treated animals, enhanced dispersion was observed compared to controls for 70 nm (12.8 ± 0.9 mm3 vs. 10.6 ± 1.0 mm3, p = 0.01), 200 nm (10.9 ± 1.4 mm3 vs. 7.4 ± 0.7 mm3, p = 0.01) and 700 nm (7.5 ± 0.4 mm3 vs. 5.4 ± 1.2 mm3, p = 0.02) nanoparticles, indicating enlargement of the interstitial spaces. No evidence of significant histological or electrophysiological injury was identified. These findings suggest that transcranial ultrasound can safely and effectively modulate the brain interstitium and increase the dispersion of large therapeutic entities such as particulate drug carriers or modified viruses. This has the potential to expand the therapeutic uses of MRgFUS. PMID:29415084

Development of a contact heat exchanger for a constructable radiator system

NASA Technical Reports Server (NTRS)

Howell, H. R.

1983-01-01

A development program for a contact heat exchanger to be used to transfer heat from a spacecraft coolant loop to a heat pipe radiator is described. The contact heat exchanger provides for a connectable/disconnectable joint which allows for on-orbit assembly of the radiator system and replacement or exchange of radiator panels for repair and maintenance. The contact heat exchanger does not require the transfer of fluid across the joint; the spacecraft coolant loop remains contained in an all welded system with no static or dynamic fluid seals. The contact interface is also "dry' with no conductive grease or interstitial material required.

Cortexin diffusion in human eye sclera

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

Genina, Elina A; Bashkatov, A N; Tuchin, Valerii V

2011-05-31

Investigation of the diffusion of cytamines, a typical representative of which is cortexin, is important for evaluating the drug dose, necessary to provide sufficient concentration of the preparation in the inner tissues of the eye. In the present paper, the cortexin diffusion rate in the eye sclera is measured using the methods of optical coherence tomography (OCT) and reflectance spectroscopy. The technique for determining the diffusion coefficient is based on the registration of temporal dependence of the eye sclera scattering parameters caused by partial replacement of interstitial fluid with the aqueous cortexin solution, which reduces the level of the OCTmore » signal and decreases the reflectance of the sclera. The values of the cortexin diffusion coefficient obtained using two independent optical methods are in good agreement. (optical technologies in biophysics and medicine)« less

The biomechanics of leg ulceration.

PubMed Central

Chant, A.

1999-01-01

Research performed in the late 1960s, using 24Na, suggested that the perfusion of skin and subcutaneous tissues is critically dependent on the relationship between capillary (Pc) and tissue pressures (Pt). Perfusion changes differed significantly between controls and patients with venous disease and the differences could be interpreted as evidence that Pt remained high in venous diseased patients. From this starting point, a biomechanical theory for the aetiology of venous ulceration was developed and tested by measuring skin elasticity, limb cross-sectional area and laser Doppler flux. The results confirm that, modelled as a two-compartment system (vascular and interstitial fluid), forces can be demonstrated sufficient to cause intermittent capillary closure and subsequent reperfusion injury. These forces are maximal in the gaiter area, the site of most leg ulcers. Images Figure 2 Figure 4 PMID:10364960

Assessment of thermal effects of interstitial laser phototherapy on mammary tumors using proton resonance frequency method

PubMed Central

Le, Kelvin; Li, Xiaosong; Figueroa, Daniel; Towner, Rheal A.; Garteiser, Philippe; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.

2011-01-01

Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11°C for 1 W and 8 to 15°C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy. PMID:22191937

Effect of electron injection on defect reactions in irradiated silicon containing boron, carbon, and oxygen

NASA Astrophysics Data System (ADS)

Makarenko, L. F.; Lastovskii, S. B.; Yakushevich, H. S.; Moll, M.; Pintilie, I.

2018-04-01

Comparative studies employing Deep Level Transient Spectroscopy and C-V measurements have been performed on recombination-enhanced reactions between defects of interstitial type in boron doped silicon diodes irradiated with alpha-particles. It has been shown that self-interstitial related defects which are immobile even at room temperatures can be activated by very low forward currents at liquid nitrogen temperatures. Their activation is accompanied by the appearance of interstitial carbon atoms. It has been found that at rather high forward current densities which enhance BiOi complex disappearance, a retardation of Ci annealing takes place. Contrary to conventional thermal annealing of the interstitial boron-interstitial oxygen complex, the use of forward current injection helps to recover an essential part of charge carriers removed due to irradiation.

Alkaline phosphatase in osteoblasts is down-regulated by pulsatile fluid flow

NASA Technical Reports Server (NTRS)

Hillsley, M. V.; Frangos, J. A.

1997-01-01

It is our hypothesis that interstitial fluid flow plays a role in the bone remodeling response to mechanical loading. The fluid flow-induced expression of three proteins (collagen, osteopontin, and alkaline phosphatase) involved in bone remodeling was investigated. Rat calvarial osteoblasts subjected to pulsatile fluid flow at an average shear stress of 5 dyne/cm2 showed decreased alkaline phosphatase (AP) mRNA expression after only 1 hour of flow. After 3 hours of flow, AP mRNA levels had decreased to 30% of stationary control levels and remained at this level for an additional 5 hours of flow. Steady flow (4 dyne/cm2 fluid shear stress), in contrast, resulted in a delayed and less dramatic decrease in AP mRNA expression to 63% of control levels after 8 hours of flow. The reduced AP mRNA expression under pulsatile flow conditions was followed by reduced AP enzyme activity after 24 hours. No changes in collagen or osteopontin mRNA expression were detected over 8 hours of pulsatile flow. This is the first time fluid flow has been shown to affect gene expression in osteoblasts.

Fluid management in critically ill patients: the role of extravascular lung water, abdominal hypertension, capillary leak, and fluid balance

PubMed Central

2012-01-01

Introduction Capillary leak in critically ill patients leads to interstitial edema. Fluid overload is independently associated with poor prognosis. Bedside measurement of intra-abdominal pressure (IAP), extravascular lung water index (EVLWI), fluid balance, and capillary leak index (CLI) may provide a valuable prognostic tool in mechanically ventilated patients. Methods We performed an observational study of 123 mechanically ventilated patients with extended hemodynamic monitoring, analyzing process-of-care variables for the first week of ICU admission. The primary outcome parameter was 28-day mortality. ΔmaxEVLWI indicated the maximum difference between EVLWI measurements during ICU stay. Patients with a ΔmaxEVLWI <−2 mL/kg were called 'responders'. CLI was defined as C-reactive protein (milligrams per deciliter) over albumin (grams per liter) ratio and conservative late fluid management (CLFM) as even-to-negative fluid balance on at least two consecutive days. Results CLI had a biphasic course. ΔmaxEVLWI was lower if CLFM was achieved and in survivors (−2.4 ± 4.8 vs 1.0 ± 5.5 mL/kg, p = 0.001; −3.3 ± 3.8 vs 2.5 ± 5.3 mL/kg, p = 0.001, respectively). No CLFM achievement was associated with increased CLI and IAPmean on day 3 and higher risk to be nonresponder (odds ratio (OR) 2.76, p = 0.046; OR 1.28, p = 0.011; OR 5.52, p = 0.001, respectively). Responders had more ventilator-free days during the first week (2.5 ± 2.3 vs 1.5 ± 2.3, p = 0.023). Not achieving CLFM and being nonresponder were strong independent predictors of mortality (OR 9.34, p = 0.001 and OR 7.14, p = 0.001, respectively). Conclusion There seems to be an important correlation between CLI, EVLWI kinetics, IAP, and fluid balance in mechanically ventilated patients, associated with organ dysfunction and poor prognosis. In this context, we introduce the global increased permeability syndrome. PMID:22873410

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis

PubMed Central

Whitmore, Kristene E

2002-01-01

The management of interstitial cystitis (IC) is predominantly the reduction of the symptoms of frequency, urgency, and pain. Multimodal treatment approaches for IC are helpful in customizing therapy for individual patients. Complementary and alternative therapies are a quintessential addition to the therapeutic armamentarium and frequently include dietary modification, nutraceuticals, bladder training, neuromodulation, stress reduction, and sex therapy. Dietary modification involves elimination of bladder irritants, fluid regulation, and a bowel regimen. Nutraceuticals studied for the treatment of IC include calcium glycerophosphate, L-arginine, mucopolysaccharides, bioflavinoids, and Chinese herbs. Bladder training is effective after pain reduction. The neuromodulation of high-tone pelvic-floor muscle dysfunction is achieved with physical therapy and acupuncture. Stress reduction and sex therapy are best administered by a qualified stress manager and sex therapist. Multimodal, nonconventional management may add efficacy to the treatment of IC. PMID:16986031

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

PubMed Central

Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

2008-01-01

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

PubMed Central

Zhang, Bo; Hu, Yu; Pang, Zhiqing

2017-01-01

Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

The distribution of serum albumin in the rat testis, studied by electron microscope immunocytochemistry on ultrathin frozen sections.

PubMed

Christensen, A K; Komorowski, T E; Wilson, B; Ma, S F; Stevens, R W

1985-05-01

The distribution of serum albumin is of interest in the rat testis because this protein is the principal carrier for testosterone in the plasma and interstitial fluid of this species. We have localized extravascular serum albumin in the rat testis at the electron microscope level, using gold particle immunocytochemistry on ultrathin frozen sections of tissue fixed lightly by perfusion. The same localization was obtained with three different antisera. Preabsorption and normal rabbit serum controls were negative, and Western blots of testis extracts showed major activity only at the molecular weight of albumin. Serum albumin occurred in substantial concentration throughout extracellular space in the interstitial tissue, as well as in the space between the boundary layer and the base of the seminiferous epithelium. Immunoreactivity extended between Sertoli cells, as well as around spermatogonia and early primary spermatocytes (to stage 11), but did not traverse the Sertoli-Sertoli junctions that comprise the blood-testis barrier. Macrophages in the interstitial tissue showed some endocytic activity. If perfusion fixation was carried out in a manner that flushed most of the albumin from the interstitial space, then a layer of albumin remained on the surface of Leydig cells and many macrophages but was minimal or absent on the surface of other cell types that are normally in contact with albumin, such as Sertoli cells, spermatogonia, myoid cells, lymphatic endothelium, fibroblasts, or cells of blood vessels.

Effects of Anti-VEGF on Predicted Antibody Biodistribution: Roles of Vascular Volume, Interstitial Volume, and Blood Flow

PubMed Central

Boswell, C. Andrew; Ferl, Gregory Z.; Mundo, Eduardo E.; Bumbaca, Daniela; Schweiger, Michelle G.; Theil, Frank-Peter; Fielder, Paul J.; Khawli, Leslie A.

2011-01-01

Background The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. Methodology/Principal Findings Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. Conclusions/Significance These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF. PMID:21436893

Subharmonic Imaging and Pressure Estimation for Monitoring Neoadjuvant Chemotherapy

DTIC Science & Technology

2014-09-01

and therapy response [10]. However, the level of IFP has been shown to predict disease free survival for cervix cancer (34% disease free survival...p. 1951-1961. 11. Milosevic M, et al., Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical...12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 Words) Neoadjuvant chemotherapy is currently the standard of care for locally advanced breast cancer

Reciprocal regulation of two G protein-coupled receptors sensing extracellular concentrations of Ca2+ and H+

PubMed Central

Wei, Wei-Chun; Jacobs, Benjamin; Becker, Esther B. E.; Glitsch, Maike D.

2015-01-01

G protein-coupled receptors (GPCRs) are cell surface receptors that detect a wide range of extracellular messengers and convey this information to the inside of cells. Extracellular calcium-sensing receptor (CaSR) and ovarian cancer gene receptor 1 (OGR1) are two GPCRs that sense extracellular Ca2+ and H+, respectively. These two ions are key components of the interstitial fluid, and their concentrations change in an activity-dependent manner. Importantly, the interstitial fluid forms part of the microenvironment that influences cell function in health and disease; however, the exact mechanisms through which changes in the microenvironment influence cell function remain largely unknown. We show that CaSR and OGR1 reciprocally inhibit signaling through each other in central neurons, and that this is lost in their transformed counterparts. Furthermore, strong intracellular acidification impairs CaSR function, but potentiates OGR1 function. Thus, CaSR and OGR1 activities can be regulated in a seesaw manner, whereby conditions promoting signaling through one receptor simultaneously inhibit signaling through the other receptor, potentiating the difference in their relative signaling activity. Our results provide insight into how small but consistent changes in the ionic microenvironment of cells can significantly alter the balance between two signaling pathways, which may contribute to disease progression. PMID:26261299

Trace metals in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases.

PubMed

Bargagli, Elena; Lavorini, Federico; Pistolesi, Massimo; Rosi, Elisabetta; Prasse, Antje; Rota, Emilia; Voltolini, Luca

2017-07-01

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an undefined etiopathogenesis. Oxidative stress contributes to alveolar injury and fibrosis development and, because transition metals are essential to the functioning of most proteins involved in redox reactions, a better knowledge of metal concentrations and metabolism in the respiratory system of IPF patients may provide a valuable complementary approach to prevent and manage a disease which is often misdiagnosed or diagnosed in later stages. The present review summarizes and discusses literature data on the elemental composition of bronchoalveolar lavage (BAL), induced sputum and exhaled breath condensate (EBC) from patients affected by IPF and healthy subjects. Available data are scanty and the lack of consistent methods for the collection and analysis of lung and airways lining fluids makes it difficult to compare the results of different studies. However, the elemental composition of BAL samples from IPF patients seems to have a specific profile that can be distinguished from that of patients with other interstitial lung diseases (ILD) or control subjects. Suggestions are given towards standard sampling and analytical procedures of BAL samples, in the aim to assess typical element concentration patterns and their potential role as biomarkers of IPF. Copyright © 2017 Elsevier GmbH. All rights reserved.

A modified method using the SonoPrep ultrasonic skin permeation system for sampling human interstitial fluid is compatible with proteomic techniques.

PubMed

Lecomte, Marie M J; Atkinson, Kelly R; Kay, Daniel P; Simons, Joanne L; Ingram, John R

2013-02-01

The use of biomarkers in skin is a novel diagnostic tool. Interstitial fluid (ISF) from skin provides a snapshot of proteins secreted at the time of sampling giving insights into the patient's health status. A minimally invasive technique for the transdermal collection of human ISF proteins. A low frequency ultrasonic skin permeation device (SonoPrep ultrasonic skin permeation system) was used to produce micropores in the stratum corneum through which ISF was extracted using a portable pulsed vacuum ISF collection device. On average, protein concentrations recovered ranged between 0.064 and 4.792 μg/μL (mean 1.258 μg/μL). Two-dimensional gel electrophoresis revealed that this sample type was amenable to this type of analysis. Gel images indicated that both highly abundant proteins and lower abundance proteins were isolated from the skin. Western blot analysis confirmed the presence of proteins commonly found in plasma and the epidermis. A minimally invasive method for the transdermal recovery of ISF proteins has been developed. We have demonstrated that ISF samples obtained using this approach can be analysed with proteomic techniques, such as two-dimensional gel electrophoresis and western blots, providing another tool for the identification of disease specific protein biomarkers. © 2012 John Wiley & Sons A/S.

Beryllium chemical speciation in elemental human biological fluids.

PubMed

Sutton, Mark; Burastero, Stephen R

2003-09-01

The understanding of beryllium chemistry in human body fluids is important for understanding the prevention and treatment of chronic beryllium disease. Thermodynamic modeling has traditionally been used to study environmental contaminant migration and rarely in the examination of metal (particularly beryllium) toxicology. In this work, a chemical thermodynamic speciation code (MINTEQA2) has been used to model and understand the chemistry of beryllium in simulated human biological fluids such as intracellular, interstitial, and plasma fluids, a number of airway surface fluids for patients with lung conditions, saliva, sweat, urine, bile, gastric juice, and pancreatic fluid. The results show that predicted beryllium solubility and speciation vary markedly between each simulated biological fluid. Formation of beryllium hydroxide and/or phosphate was observed in most of the modeled fluids, and results support the postulation that beryllium absorption in the gastrointestinal tract may be limited by the formation of beryllium phosphate solids. It is also postulated that beryllium is potentially 13% less soluble in the airway surface fluid of a patient with asthma when compared to a "normal" case. The results of this work, supported by experimental validation, can aid in the understanding of beryllium toxicology. Our results can potentially be applied to assessing the feasibility of biological monitoring or chelation treatment of beryllium body burden.

Impact of hydrogen and oxygen defects on the lattice parameter of chemical vapor deposited zinc sulfide

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

McCloy, John S.; Wolf, Walter; Wimmer, Erich

2013-01-09

The lattice parameter of cubic chemical vapor deposited (CVD) ZnS with measured oxygen concentrations < 0.6 at.% and hydrogen impurities of < 0.015 at.% have been measured and found to vary between -0.10% and +0.09% relative to the reference lattice parameter (5.4093 Å) of oxygen-free cubic ZnS as reported in the literature. Defects other than substitutional O must be invoked to explain these observed volume changes. The structure and thermodynamic stability of a wide range of native and impurity induced defects in ZnS have been determined by Ab initio calculations. Lattice contraction is caused by S-vacancies, substitutional O on Smore » sites, Zn vacancies, H in S vacancies, peroxy defects, and dissociated water in S-vacancies. The lattice is expanded by interstitial H, H in Zn vacancies, dihydroxy defects, interstitial oxygen, Zn and [ZnHn] complexes (n=1,…,4), interstitial Zn, and S2 dumbbells. Oxygen, though present, likely forms substitutional defects for sulfur resulting in lattice contraction rather than as interstitial oxygen resulting in lattice expansion. It is concluded based on measurement and calculations that excess zinc atoms either at anti-sites (i.e. Zn atoms on S-sites) or possibly as interstitial Zn are responsible for the relative increase of the lattice parameter of commercially produced CVD ZnS.« less

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

PubMed Central

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

Cot-side electro-encephalography and interstitial glucose monitoring during insulin-induced hypoglycaemia in newborn lambs.

PubMed

Harris, Deborah L; Battin, Malcolm R; Williams, Chris E; Weston, Philip J; Harding, Jane E

2009-01-01

The optimal approach to detection and management of neonatal hypoglycaemia remains unclear. We sought to demonstrate whether electro-encephalography (EEG) changes could be detected on the amplitude-integrated EEG monitor during induced hypoglycaemia in newborn lambs, and also to determine the accuracy of continuously measured interstitial glucose in this situation. Needle electrodes were placed in the P3-P4, O1-O2 montages. The interstitial glucose sensor was placed subcutaneously. After 30 min baseline recordings, hypoglycaemia was induced by insulin infusion and blood glucose levels were monitored every 5 min. The infusion was adjusted to reduce blood glucose levels by 0.5 mmol/l every 15 min and then maintain a blood glucose level <1.0 mmol/l for 4 h. EEG parameters analysed included amplitude, continuity and spectral edge frequency. The interstitial and blood glucose levels were compared. All lambs (n = 15, aged 3-11 days) became hypoglycaemic, with median blood glucose levels falling from 6.5 to 1.0 mmol/l, p < 0.0001. There were no detectable changes in any of the measured EEG parameters related to hypoglycaemia, although seizures occurred in 2 lambs. There was moderate agreement between the intermittent blood glucose and continuous interstitial glucose measurements in the baseline, decline, and hypoglycaemia periods (mean difference -0.7 mmol/l, 95% confidence interval, CI, -2.8 to 1.4 mmol/l). However, agreement was poor during reversal of hypoglycaemia (mean difference 4.5 mmol/l, 95% CI -1.1 to 10.7 mmol/l). The cot-side EEG may not be a useful clinical tool in the detection of neurological changes induced by hypoglycaemia. However, continuous interstitial glucose monitoring may be useful in the management of babies at risk of hypoglycaemia. (c) 2008 S. Karger AG, Basel.

Effect of cadmium in sediments on colonization by benthic marine organisms: Role of interstitial cadmium and acid volatile sulfide in bioavailability

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

Hansen, D.; Berry, W.; Benyi, S.

1995-12-31

The role of interstitial cadmium and acid volatile sulfide (AVS) in controlling the bioavailability of sediment-associated metal was examined using the chronic saltwater benthic colonization test. Sediments were spiked with cadmium to achieve simultaneously extracted metal (SEM)/AVS molar ratios of 0. 0 (control), 0.1, 0.8 and 3.0 in this 118-day test. Oxidation of AVS in the surficial 2.4 cm within two to four weeks resulted in sulfide profiles similar to those occurring naturally in local sediments. In the nominal 0.1 SEM/AVS treatment, measured SEM was always less than AVS. Interstitial cadmium concentrations (< 3--10 {micro}g/L) were below those likely tomore » cause biological effects. No significant biological effects were detected. In the nominal 0.8 SEM/AVS treatment, measured SEM commonly exceeded AVS in the surficial 2.4 cm of sediment. Interstitial cadmium concentrations (24--157 {micro}g/L) were likely of toxicological significance to sensitive species. Shifts were observed in presence/absence of species, and there were fewer macrobenthic polychaetes (Mediomastus ambiseta, Strebloapio benedicti and Podarke obscura) and unidentified meiofaunal nematodes. In the nominal 3.0 SEM/AVS treatment, concentrations of SEM were always greater than AVS throughout the sediment column. Interstitial cadmium ranged from 28,000 to 174,000 {micro}g/L. In addition to the effects above, these sediments were colonized by fewer macrobenthic species, polychaete species and harpacticoids; had lower densities of diatoms; lacked bivalve molluscs and exhibited other impacts. The observed biological responses were consistent with measured SEM/AVS ratios in surficial sediments and interstitial water cadmium concentrations, further supporting their utility in predicting metals bioavailability.« less

Amelioration of ischemic brain damage by peritoneal dialysis

PubMed Central

Godino, María del Carmen; Romera, Victor G.; Sánchez-Tomero, José Antonio; Pacheco, Jesus; Canals, Santiago; Lerma, Juan; Vivancos, José; Moro, María Angeles; Torres, Magdalena; Lizasoain, Ignacio; Sánchez-Prieto, José

2013-01-01

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients. PMID:23999426

Massive ovarian edema associated with a broad ligament leiomyoma: a case report and review.

PubMed

Harrison, Beth T; Berg, Robert E; Mittal, Khush

2014-07-01

Massive ovarian edema is a rare disorder in which there is marked accumulation of interstitial fluid in the stroma of the ovary. Grossly, the involved ovary is an enlarged solid mass with a smooth tan-white surface, easily confused with a neoplasm. Microscopically, it features diffuse interstitial edema sparing follicles and outer cortex, dilated lymphatic vessels, thick-walled veins, fibromatosis, and luteinized stromal cells. It is believed that massive ovarian edema arises from interference in lymphatic drainage and venous return of the ovary secondary to partial torsion among other etiologies. Herein we provide the first description of unilateral ovarian edema in association with a large leiomyoma in the ipsilateral broad ligament. It is important to recognize the various presentations of this benign entity and to consider it in the differential diagnosis of an adnexal mass in a reproductive age woman.

Structural effects in the interstitial solid solution system (La,Ce)(Fe,Si)13Cx-H: Correlation with hydrogenation kinetics

NASA Astrophysics Data System (ADS)

Hai, X.; Porcher, F.; Mayer, C.; Miraglia, S.

2018-02-01

Steady state and in-situ neutron powder diffraction on selected compositions of the magneto-caloric (La,Ce)(Fe,Si)13CxHy compounds has been used to locate the sites accommodated by the interstitial species and to reveal the structural modifications (breathing) that occur upon metal substitution and/or interstitial insertion. The latter type of measurement in which the sequential filling of interstitial sites is followed allows one to extract some useful hydrogenation kinetics data. This structural investigation has allowed to precise the deformations undergone by the complex metallic alloys La(Fe,Si)13 when subjected to light interstitial insertion or rare earth substitution at the cation site of the NaZn13-structure type. We attempt to correlate hydrogenation kinetics variations (depression or enhancement of the hydrogen absorption rate) with a particular inhomogeneous cell variation (breathing) and bonding of the NaZn13 structure-type.

Role of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea.

PubMed

White, Laura H; Bradley, T Douglas

2013-03-01

Obstructive sleep apnoea (OSA) is common in the general population and increases the risk of motor vehicle accidents due to hypersomnolence from sleep disruption, and risk of cardiovascular diseases owing to repetitive hypoxia, sympathetic nervous system activation, and systemic inflammation. In contrast, central sleep apnoea (CSA) is rare in the general population. Although their pathogenesis is multifactorial, the prevalence of both OSA and CSA is increased in patients with fluid retaining states, especially heart failure, where they are associated with increased mortality risk. This observation suggests that fluid retention may contribute to the pathogenesis of both OSA and CSA. According to this hypothesis, during the day fluid accumulates in the intravascular and interstitial spaces of the legs due to gravity, and upon lying down at night redistributes rostrally, again owing to gravity. Some of this fluid may accumulate in the neck, increasing tissue pressure and causing the upper airway to narrow, thereby increasing its collapsibility and predisposing to OSA. In heart failure patients, with increased rostral fluid shift, fluid may additionally accumulate in the lungs, provoking hyperventilation and hypocapnia, driving below the apnoea threshold, leading to CSA. This review article will explore mechanisms by which overnight rostral fluid shift, and its prevention, can contribute to the pathogenesis and therapy of sleep apnoea.

Role of nocturnal rostral fluid shift in the pathogenesis of obstructive and central sleep apnoea

PubMed Central

White, Laura H; Bradley, T Douglas

2013-01-01

Obstructive sleep apnoea (OSA) is common in the general population and increases the risk of motor vehicle accidents due to hypersomnolence from sleep disruption, and risk of cardiovascular diseases owing to repetitive hypoxia, sympathetic nervous system activation, and systemic inflammation. In contrast, central sleep apnoea (CSA) is rare in the general population. Although their pathogenesis is multifactorial, the prevalence of both OSA and CSA is increased in patients with fluid retaining states, especially heart failure, where they are associated with increased mortality risk. This observation suggests that fluid retention may contribute to the pathogenesis of both OSA and CSA. According to this hypothesis, during the day fluid accumulates in the intravascular and interstitial spaces of the legs due to gravity, and upon lying down at night redistributes rostrally, again owing to gravity. Some of this fluid may accumulate in the neck, increasing tissue pressure and causing the upper airway to narrow, thereby increasing its collapsibility and predisposing to OSA. In heart failure patients, with increased rostral fluid shift, fluid may additionally accumulate in the lungs, provoking hyperventilation and hypocapnia, driving below the apnoea threshold, leading to CSA. This review article will explore mechanisms by which overnight rostral fluid shift, and its prevention, can contribute to the pathogenesis and therapy of sleep apnoea. PMID:23230237

On the Opening of Thick Walled Elastic Tubes: A Fluid-Structure Model for Acid Reflux

NASA Astrophysics Data System (ADS)

Ghosh, Sudip; Kahrilas, Peter

2005-11-01

A coupled fluid-structure mathematical model was developed to quantify rapid opening of thick-walled elastic tubes, a phenomenon underlying biological flows such as gastroesophageal reflux disease (GERD). The wall was modeled using non-linear finite deformation theory to predict space-time radial distention of an axisymmetric tube with luminal fluid flow. Anisotropic azimuthal and longitudinal muscle-induced stresses were incorporated, and interstitial material properties were assumed isotropic and linearly elastic. Fluid flow was modeled using lubrication theory with inertial correction. Opening and flow were driven by a specified inflow pressure and zero pressure gradient was specified at outflow. No-slip and surface force balance were applied at the fluid-wall interface. Viscoelasticity was modeled with ad hoc damping and the evolution of the tube geometry was predicted at mid-layer. A potentially important discovery was made when applied to studies of initiation of opening with GERD: while material stiffness is of minor consequence, small changes in resting lumen distension (˜2 mm diameter) may be a sensitive distinguishing feature of the disease.

Addressing the need for biomarker liquid chromatography/mass spectrometry assays: a protocol for effective method development for the bioanalysis of endogenous compounds in cerebrospinal fluid.

PubMed

Benitex, Yulia; McNaney, Colleen A; Luchetti, David; Schaeffer, Eric; Olah, Timothy V; Morgan, Daniel G; Drexler, Dieter M

2013-08-30

Research on disorders of the central nervous system (CNS) has shown that an imbalance in the levels of specific endogenous neurotransmitters may underlie certain CNS diseases. These alterations in neurotransmitter levels may provide insight into pathophysiology, but can also serve as disease and pharmacodynamic biomarkers. To measure these potential biomarkers in vivo, the relevant sample matrix is cerebrospinal fluid (CSF), which is in equilibrium with the brain's interstitial fluid and circulates through the ventricular system of the brain and spinal cord. Accurate analysis of these potential biomarkers can be challenging due to low CSF sample volume, low analyte levels, and potential interferences from other endogenous compounds. A protocol has been established for effective method development of bioanalytical assays for endogenous compounds in CSF. Database searches and standard-addition experiments are employed to qualify sample preparation and specificity of the detection thus evaluating accuracy and precision. This protocol was applied to the study of the histaminergic neurotransmitter system and the analysis of histamine and its metabolite 1-methylhistamine in rat CSF. The protocol resulted in a specific and sensitive novel method utilizing pre-column derivatization ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS), which is also capable of separating an endogenous interfering compound, identified as taurine, from the analytes of interest. Copyright © 2013 John Wiley & Sons, Ltd.

Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol

PubMed Central

Le, D. Elizabeth; Pascotto, Marco; Leong-Poi, Howard; Sari, Ibrahim; Micari, Antonio; Kaul, Sanjiv

2013-01-01

There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment endsystolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses of these drugs. PMID:24072434

Interactive effect of chondroitin sulphate C and hyaluronan on fluid movement across rabbit synovium

PubMed Central

Sabaratnam, S; Coleman, P J; Badrick, E; Mason, R M; Levick, J R

2002-01-01

The polysaccharide hyaluronan (HA) conserves synovial fluid by keeping outflow low and almost constant over a wide pressure range (‘buffering’), but only at concentrations associated with polymer domain overlap. We therefore tested whether polymer interactions can cause buffering, using HA-chondroitin sulphate C (CSC) mixtures. Also, since it has been found that capillary filtration is insensitive to the Starling force interstitial osmotic pressure in frog mesenteries, this was assessed in synovium. Hyaluronan at non-buffering concentrations (0.50–0.75 mg ml−1) and/or 25 mg ml−1 CSC (osmotic pressure 68 cmH2O) was infused into knees of anaesthetised rabbits in vivo. Viscometry and chromatography confirmed that HA interacts with CSC. Pressure (Pj) versus trans-synovial flow (Q̇s) relations were measured. Q̇s was outwards for HA alone (1.2 ± 0.9 μl min−1 at 3 cmH2O, mean ± s.e.m.; n = 6). CSC diffused into synovium and changed Q̇s to filtration at low Pj (−4.1 μl min−1, 3 cmH2O, n = 5, P < 0.02, t test). Filtration ceased upon circulatory arrest (n = 3). At higher Pj, 0.75 mg ml−1 HA plus CSC buffered Q̇s to ∼3 μl min−1 over a wide range of Pj, with an outflow increase of only 0.04 ± 0.02 μl min−1 cmH2O−1 (n = 4). With HA or CSC alone, buffering was absent (slopes 0.57 ± 0.04 μl min−1 cmH2O−1 (n = 4) and 0.86 ± 0.05 μl min−1 cmH2O−1 (n = 5), respectively). Therefore, polymer interactions can cause outflow buffering in joints. Also, interstitial osmotic pressure promoted filtration in fenestrated synovial capillaries, so the results for frog mesentery capillaries cannot be generalised. The difference is attributed to differences in pore ultrastructure. PMID:11927686

Intravital imaging of osteocytes in mouse calvaria using third harmonic generation microscopy

PubMed Central

Cisek, Richard; Wein, Marc N.; Turcotte, Raphaël; Haase, Christa; Yeh, Shu-Chi A.; Bharadwaj, Srinidhi; Raphael, Anthony P.; Paudel, Hari; Alt, Clemens; Liu, Tzu-Ming; Kronenberg, Henry M.; Lin, Charles P.

2017-01-01

Osteocytes are the most abundant cell in the bone, and have multiple functions including mechanosensing and regulation of bone remodeling activities. Since osteocytes are embedded in the bone matrix, their inaccessibility makes in vivo studies problematic. Therefore, a non-invasive technique with high spatial resolution is desired. The purpose of this study is to investigate the use of third harmonic generation (THG) microscopy as a noninvasive technique for high-resolution imaging of the lacunar-canalicular network (LCN) in live mice. By performing THG imaging in combination with two- and three-photon fluorescence microscopy, we show that THG signal is produced from the bone-interstitial fluid boundary of the lacuna, while the interstitial fluid-osteocyte cell boundary shows a weaker THG signal. Canaliculi are also readily visualized by THG imaging, with canaliculi oriented at small angles relative to the optical axis exhibiting stronger signal intensity compared to those oriented perpendicular to the optical axis (parallel to the image plane). By measuring forward- versus epi-detected THG signals in thinned versus thick bone samples ex vivo, we found that the epi-collected THG from the LCN of intact bone contains a superposition of backward-directed and backscattered forward-THG. As an example of a biological application, THG was used as a label-free imaging technique to study structural variations in the LCN of live mice deficient in both histone deacetylase 4 and 5 (HDAC4, HDAC5). Three-dimensional analyses were performed and revealed statistically significant differences between the HDAC4/5 double knockout and wild type mice in the number of osteocytes per volume and the number of canaliculi per lacunar surface area. These changes in osteocyte density and dendritic projections occurred without differences in lacunar size. This study demonstrates that THG microscopy imaging of the LCN in live mice enables quantitative analysis of osteocytes in animal models without the use of dyes or physical sectioning. PMID:29065178

Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.

PubMed

Hompland, Tord; Ellingsen, Christine; Rofstad, Einar K

2012-11-22

High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.

Biogenic Weathering: Solubilization of Iron from Minerals by Epilithic Freshwater Algae and Cyanobacteria

PubMed Central

2018-01-01

A sandstone outcrop exposed to freshwater seepage supports a diverse assemblage of photosynthetic microbes. Dominant taxa are two cyanophytes (Oscillatoria sp., Rivularia sp.) and a unicellular green alga (Palmellococcus sp.). Less abundant taxa include a filamentous green alga, Microspora, and the desmid Cosmarium. Biologic activity is evidenced by measured levels of chlorophyll and lipids. Bioassay methods confirm the ability of these microbes to dissolve and metabolize Fe from ferruginous minerals. Chromatographic analysis reveals citric acid as the likely chelating agent; this low molecular weight organic acid is detectable in interstitial fluid in the sandstone, measured as 0.0756 mg/mL. Bioassays using a model organism, Synechoccus elongates strain UTEX 650, show that Fe availability varies among different ferruginous minerals. In decreasing order of Fe availability: magnetite > limonite > biotite > siderite > hematite. Biotite was selected for detailed study because it is the most abundant iron-bearing mineral in the sandstone. SEM images support the microbiologic evidence, showing weathering of biotite compared to relatively undamaged grains of other silicate minerals. PMID:29342973

Modern Chemistry Techniques Applied to Metal Behavior and Chelation in Medical and Environmental Systems ? Final Report

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

Sutton, M; Andresen, B; Burastero, S R

2005-02-03

This report details the research and findings generated over the course of a 3-year research project funded by Lawrence Livermore National Laboratory (LLNL) Laboratory Directed Research and Development (LDRD). Originally tasked with studying beryllium chemistry and chelation for the treatment of Chronic Beryllium Disease and environmental remediation of beryllium-contaminated environments, this work has yielded results in beryllium and uranium solubility and speciation associated with toxicology; specific and effective chelation agents for beryllium, capable of lowering beryllium tissue burden and increasing urinary excretion in mice, and dissolution of beryllium contamination at LLNL Site 300; {sup 9}Be NMR studies previously unstudied atmore » LLNL; secondary ionization mass spec (SIMS) imaging of beryllium in spleen and lung tissue; beryllium interactions with aerogel/GAC material for environmental cleanup. The results show that chelator development using modern chemical techniques such as chemical thermodynamic modeling, was successful in identifying and utilizing tried and tested beryllium chelators for use in medical and environmental scenarios. Additionally, a study of uranium speciation in simulated biological fluids identified uranium species present in urine, gastric juice, pancreatic fluid, airway surface fluid, simulated lung fluid, bile, saliva, plasma, interstitial fluid and intracellular fluid.« less

Fluid flow stimulates rapid and continuous release of nitric oxide in osteoblasts

NASA Technical Reports Server (NTRS)

Johnson, D. L.; McAllister, T. N.; Frangos, J. A.

1996-01-01

Interstitial fluid flow may mediate skeletal remodeling in response to mechanical loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and inhibitor of osteoclastic resorption, we investigated and characterized the role of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a stationary culture produced undetectable levels of NO. Fluid shear stress (6 dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and sustained this production for 12 h of exposure to flow. Cytokine treatment also induced NO synthesis after a 12-h lag phase of zero production, followed by a production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by dexamethasone, which suggests that the flow stimulated a constitutive NOS isoform. This is the first time that a functional constitutively present NOS isoform has been identified in osteoblasts. Moreover, fluid flow represents the most potent stimulus of NO release in osteoblasts reported to date. Fluid flow-induced NO production may therefore play a primary role in bone maintenance and remodeling.

Edema is a precursor to central nervous system peritumoral cyst formation.

PubMed

Lonser, Russell R; Vortmeyer, Alexander O; Butman, John A; Glasker, Sven; Finn, Michael A; Ammerman, Joshua M; Merrill, Marsha J; Edwards, Nancy A; Zhuang, Zhengping; Oldfield, Edward H

2005-09-01

Despite the common occurrence and frequent clinical effects of peritumoral cysts in the central nervous system (CNS), the mechanism underlying their development and evolution is not understood. Because they commonly produce peritumoral cysts and because serial magnetic resonance imaging (MRI) is obtained in von Hippel-Lindau disease patients, hemangioblastomas provide an opportunity to examine the pathophysiology of CNS peritumoral cyst formation. Serial MRI was correlated with the clinical findings in 16 von Hippel-Lindau disease patients with 22 CNS hemangioblastomas (11 spinal cord; 11 cerebellar) that were associated with the appearance and evolution of peritumoral cysts. Hemangioblastoma-associated cyst wall histomorphological analysis was performed on postmortem tissues from three von Hippel-Lindau disease patients (not in the clinical series). Comparative proteomic profiling was performed on peritumoral cyst fluid and serum. Vascular endothelial growth factor levels were determined in peritumoral cysts. MRI clearly showed peritumoral edema that developed and slowly and progressively evolved into enlarging hemangioblastoma-associated cysts in all tumors (mean follow-up, 130 +/- 38 months; mean +/- standard deviation). Postcontrast MRI demonstrated convective leakage of gadolinium into cysts. Mean time required for edema to evolve into a cyst was 36 +/- 23 months (range, 8-72 months). Thirteen (59%) hemangioblastoma-cysts became symptomatic (mean time to symptom formation after cyst development, 35 +/- 32 months; range, 3-102 months) and required resection. Protein profiles of cyst fluid and serum were similar. Mean cyst fluid vascular endothelial growth factor concentration was 1.5 ng/ml (range, 0-5.4 ng/ml). Histology of the cyst walls was consistent with reactive gliosis. CNS peritumoral cyst formation is initiated by increased tumor vascular permeability, increased interstitial pressure in the tumor, and plasma extravasation with convective distribution into the surrounding tissue. When the delivery of plasma from the tumor exceeds the capacity of the surrounding tissue to absorb the extravasated fluid, edema (with its associated increased interstitial pressure) and subsequent cyst formation occur.

Improved intratumoral nanoparticle extravasation and penetration by mild hyperthermia.

PubMed

Li, Li; ten Hagen, Timo L M; Bolkestein, Michiel; Gasselhuber, Astrid; Yatvin, Jeremy; van Rhoon, Gerard C; Eggermont, Alexander M M; Haemmerich, Dieter; Koning, Gerben A

2013-04-28

Accumulation of nanoparticles in solid tumors depends on their extravasation. However, vascular permeability is very heterogeneous within a tumor and among different tumor types, hampering efficient delivery. Local hyperthermia at a tumor can improve nanoparticle delivery by increasing tumor vasculature permeability, perfusion and interstitial fluid flow. The aim of this study is to investigate hyperthermia conditions required to improve tumor vasculature permeability, subsequent liposome extravasation and interstitial penetration in 4 tumor models. Tumors are implanted in dorsal skin flap window chambers and observed for liposome (~85 nm) accumulation by intravital confocal microscopy. Local hyperthermia at 41°C for 30 min initiates liposome extravasation through permeable tumor vasculature in all 4 tumor models. A further increase in nanoparticle extravasation occurs while continuing heating to 1h, which is a clinically relevant duration. After hyperthermia, the tumor vasculature remains permeable for 8h. We visualize gaps in the endothelial lining of up to 10 μm induced by HT. Liposomes extravasate through these gaps and penetrate into the interstitial space to at least 27.5 μm in radius from the vessel walls. Whole body optical imaging confirms HT induced extravasation while liposome extravasation was absent at normothermia. In conclusion, a thermal dose of 41°C for 1h is effective to induce long-lasting permeable tumor vasculature for liposome extravasation and interstitial penetration. These findings hold promise for improved intratumoral drug delivery upon application of local mild hyperthermia prior to administration of nanoparticle-based drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Alzheimer CSF biomarkers may be misleading in normal-pressure hydrocephalus

PubMed Central

2014-01-01

Objective: This article discusses why CSF biomarkers found in normal-pressure hydrocephalus (NPH) can be misleading when distinguishing NPH from comorbid NPH with Alzheimer disease (AD). Methods: We describe NPH CSF biomarkers and how shunt surgery can change them. We hypothesize the effects that hydrocephalus may play on interstitial fluid space and amyloid precursor protein (APP) fragment drainage into the CSF based on a recent report and how this may explain the misleading CSF NPH biomarker findings. Results: In NPH, β-amyloid protein 42 (Aβ42) is low (as in AD), but total tau (t-tau) and phospho-tau (p-tau) levels are normal, providing conflicting biomarker findings. Low Aβ42 supports an AD diagnosis but tau findings do not. Importantly, not only Aβ42, but all APP fragments and tau proteins are low in NPH CSF. Further, these proteins increase after shunting. An increase in interstitial space and APP fragment drainage into the CSF during sleep was reported recently. Conclusions: In the setting of hydrocephalus when the brain is compressed, a decrease in interstitial space and APP protein fragment drainage into the CSF may be impeded, resulting in low levels of all APP fragments and tau proteins, which has been reported. Shunting, which decompresses the brain, would create more room for the interstitial space to increase and protein waste fragments to drain into the CSF. In fact, CSF proteins increase after shunting. CSF biomarkers in pre-shunt NPH have low Aβ42 and tau protein levels, providing misleading information to distinguish NPH from comorbid NPH plus AD. PMID:25332445

Hydrodynamically-driven drug release during interstitial flow through hollow fibers implanted near lymphatics

PubMed Central

Dukhin, Stanislav S.; Labib, Mohamed E.

2016-01-01

Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional to the number of hollow fibers in the fabric employed in drug delivery. Based on this contribution, it is now possible to simultaneously provide high release rates and long release durations, thus overcoming a fundamental limitation in drug delivery. Perhaps this breakthrough in long-term drug delivery has potential applications in targeting lymphatics and in treating cancer and cancer metastasis without causing the serious side effects of systemic drugs. PMID:28579697

Transient viscous response of the human cornea probed with the Surface Force Apparatus.

PubMed

Zappone, Bruno; Patil, Navinkumar J; Lombardo, Marco; Lombardo, Giuseppe

2018-01-01

Knowledge of the biomechanical properties of the human cornea is crucial for understanding the development of corneal diseases and impact of surgical treatments (e.g., corneal laser surgery, corneal cross-linking). Using a Surface Force Apparatus we investigated the transient viscous response of the anterior cornea from donor human eyes compressed between macroscopic crossed cylinders. Corneal biomechanics was analyzed using linear viscoelastic theory and interpreted in the framework of a biphasic model of soft hydrated porous tissues, including a significant contribution from the pressurization and viscous flow of fluid within the corneal tissue. Time-resolved measurements of tissue deformation and careful determination of the relaxation time provided an elastic modulus in the range between 0.17 and 1.43 MPa, and fluid permeability of the order of 10-13 m4/(N∙s). The permeability decreased as the deformation was increased above a strain level of about 10%, indicating that the interstitial space between fibrils of the corneal stromal matrix was reduced under the effect of strong compression. This effect may play a major role in determining the observed rate-dependent non-linear stress-strain response of the anterior cornea, which underlies the shape and optical properties of the tissue.

Development and Validation of Computational Fluid Dynamics Models for Prediction of Heat Transfer and Thermal Microenvironments of Corals

PubMed Central

Ong, Robert H.; King, Andrew J. C.; Mullins, Benjamin J.; Cooper, Timothy F.; Caley, M. Julian

2012-01-01

We present Computational Fluid Dynamics (CFD) models of the coupled dynamics of water flow, heat transfer and irradiance in and around corals to predict temperatures experienced by corals. These models were validated against controlled laboratory experiments, under constant and transient irradiance, for hemispherical and branching corals. Our CFD models agree very well with experimental studies. A linear relationship between irradiance and coral surface warming was evident in both the simulation and experimental result agreeing with heat transfer theory. However, CFD models for the steady state simulation produced a better fit to the linear relationship than the experimental data, likely due to experimental error in the empirical measurements. The consistency of our modelling results with experimental observations demonstrates the applicability of CFD simulations, such as the models developed here, to coral bleaching studies. A study of the influence of coral skeletal porosity and skeletal bulk density on surface warming was also undertaken, demonstrating boundary layer behaviour, and interstitial flow magnitude and temperature profiles in coral cross sections. Our models compliment recent studies showing systematic changes in these parameters in some coral colonies and have utility in the prediction of coral bleaching. PMID:22701582

Mechanosensitive β-catenin signaling regulates lymphatic vascular development

PubMed Central

Cha, Boksik; Srinivasan, R. Sathish

2016-01-01

The Wnt/β-catenin signaling is an evolutionarily conserved pathway that plays a pivotal role in embryonic development and adult homeostasis. However, we have limited information about the involvement of Wnt/β-catenin signaling in the lymphatic vascular system that regulates fluid homeostasis by absorbing interstitial fluid and returning it to blood circulation. In this recent publication we report that canonical Wnt/β-catenin signaling is highly active and critical for the formation of lymphovenus valves (LVVs) and lymphatic valves (LVs). β-catenin directly associates with the regulatory elements of the lymphedema-associated transcription factor, FOXC2 and activates its expression in an oscillatory shear stress (OSS)-dependent manner. The phenotype of β-catenin null embryos was rescued by FOXC2 overexpression. These results suggest that Wnt/β-catenin signaling is a mechanotransducer that links fluid force with lymphatic vascular development. [BMB Reports 2016; 49(8): 403-404] PMID:27418286

Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

PubMed Central

Padilla-Zambrano, Huber S.; Tomás-Zapico, Cristina; García, Benjamin Fernández

2018-01-01

This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain. PMID:29570693

Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson's Disease.

PubMed

Menéndez-González, Manuel; Padilla-Zambrano, Huber S; Tomás-Zapico, Cristina; García, Benjamin Fernández

2018-03-23

This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson's disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain.

Direct observation of cerebrospinal fluid bulk flow in the brain

NASA Astrophysics Data System (ADS)

Mestre, Humberto; Tithof, Jeffrey; Thomas, John; Kelley, Douglas; Nedergaard, Maiken

2017-11-01

Cerebrospinal fluid (CSF) serves a vital role in normal brain function. Its adequate flow and exchange with interstitial fluid through perivascular spaces (PVS) has been shown to be important in the clearance of toxic metabolites like amyloid- β, and its disturbance can cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have prevented direct observation of such flows in the PVS. In this talk, we describe a novel approach using high speed two photon laser scanning microscopy which has allowed for the first ever direct observation of CSF flow in the PVS of a mouse brain. By performing particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry. This technique enables future studies of CSF flow disturbances on a new scale and will pave the way for evaluating the role of these fluxes in neurodegenerative disease. R01NS100366 (to M.N.).

Hydrogel-based electrochemical sensor for non-invasive and continuous glucose monitoring

NASA Astrophysics Data System (ADS)

Park, Habeen; Lee, Ji-Young; Kim, Dong-Chul; Koh, Younggook; Cha, Junhoe

2017-07-01

Monitoring blood glucose level of diabetic patients is crucial in diabetes care from life threating complications. Selfmonitoring blood glucose (SMBG) that involves finger prick to draw blood samples into the measurement system is a widely-used method of routine measurement of blood glucose levels to date. SMBG includes, however, unavoidable pain problems resulting from the repetitive measurements. We hereby present a hydrogel-based electrochemical (H-EC) sensor to monitor the glucose level, non-invasively. Glucose oxidase (GOx) was immobilized in the disc-type hydroxyethyl methacrylate (HEMA) based hydrogel and kept intact in the hydrogel. Fast electron transfer mediated by Prussian blue (PB, hexacyanoferrate) generated efficient signal amplifications to facilitate the detection of the extracted glucose from the interstitial fluid. The linear response and the selectivity against glucose of the H-EC sensor were validated by chronoamperometry. For the practical use, the outcomes from the correlation of the extracted glucose concentration and the blood glucose value by on-body extraction, as well as the validation of the hydrogel-based electrochemical (H-EC) device, were applied to the on-body glucose monitoring.

Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides.

PubMed

Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

2013-10-15

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin-angiotensin-aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nM) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P = 0.01, n = 7) and 2.7 ± 0.8-fold (P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P = 0.005) and frequency (P = 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

PubMed

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

A Conspicuous Clay Ovoid in Nakhla: Evidence for Subsurface Hydrothermal Alteration on Mars with Implications for Astrobiology

PubMed Central

Haigh, Sarah; Lyon, Ian

2014-01-01

Abstract A conspicuous biomorphic ovoid structure has been discovered in the Nakhla martian meteorite, made of nanocrystalline iron-rich saponitic clay and amorphous material. The ovoid is indigenous to Nakhla and occurs within a late-formed amorphous mesostasis region of rhyolitic composition that is interstitial to two clinopyroxene grains with Al-rich rims, and contains acicular apatite crystals, olivine, sulfides, Ti-rich magnetite, and a new mineral of the rhoenite group. To infer the origin of the ovoid, a large set of analytical tools was employed, including scanning electron microscopy and backscattered electron imaging, wavelength-dispersive X-ray analysis, X-ray mapping, Raman spectroscopy, time-of-flight secondary ion mass spectrometry analysis, high-resolution transmission electron microscope imaging, and atomic force microscope topographic mapping. The concentric wall of the ovoid surrounds an originally hollow volume and exhibits internal layering of contrasting nanotextures but uniform chemical composition, and likely inherited its overall shape from a preexisting vesicle in the mesostasis glass. A final fibrous layer of Fe-rich phases blankets the interior surfaces of the ovoid wall structure. There is evidence that the parent rock of Nakhla has undergone a shock event from a nearby bolide impact that melted the rims of pyroxene and the interstitial matter and initiated an igneous hydrothermal system of rapidly cooling fluids, which were progressively mixed with fluids from the melted permafrost. Sharp temperature gradients were responsible for the crystallization of Al-rich clinopyroxene rims, rhoenite, acicular apatites, and the quenching of the mesostasis glass and the vesicle. During the formation of the ovoid structure, episodic fluid infiltration events resulted in the precipitation of saponite rinds around the vesicle walls, altered pyrrhotite to marcasite, and then isolated the ovoid wall structure from the rest of the system by depositing a layer of iron oxides/hydroxides. Carbonates, halite, and sulfates were deposited last within interstitial spaces and along fractures. Among three plausible competing hypotheses here, this particular abiotic scenario is considered to be the most reasonable explanation for the formation of the ovoid structure in Nakhla, and although compelling evidence for a biotic origin is lacking, it is evident that the martian subsurface contains niche environments where life could develop. Key Words: Biomorph—Clays—Search for life (biosignatures)—Martian meteorites—Hydrothermal systems. Astrobiology 14, 651–693. PMID:25046549

Invasive and non-invasive measurement in medicine and biology: calibration issues

NASA Astrophysics Data System (ADS)

Rolfe, P.; Zhang, Yan; Sun, Jinwei; Scopesi, F.; Serra, G.; Yamakoshi, K.; Tanaka, S.; Yamakoshi, T.; Yamakoshi, Y.; Ogawa, M.

2010-08-01

Invasive and non-invasive measurement sensors and systems perform vital roles in medical care. Devices are based on various principles, including optics, photonics, and plasmonics, electro-analysis, magnetics, acoustics, bio-recognition, etc. Sensors are used for the direct insertion into the human body, for example to be in contact with blood, which constitutes Invasive Measurement. This approach is very challenging technically, as sensor performance (sensitivity, response time, linearity) can deteriorate due to interactions between the sensor materials and the biological environment, such as blood or interstitial fluid. Invasive techniques may also be potentially hazardous. Alternatively, sensors or devices may be positioned external to the body surface, for example to analyse respired breath, thereby allowing safer Non-Invasive Measurement. However, such methods, which are inherently less direct, often requiring more complex calibration algorithms, perhaps using chemometric principles. This paper considers and reviews the issue of calibration in both invasive and non-invasive biomedical measurement systems. Systems in current use usually rely upon periodic calibration checks being performed by clinical staff against a variety of laboratory instruments and QC samples. These procedures require careful planning and overall management if reliable data are to be assured.

The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication.

PubMed

Béhar, A; Pujade-Lauraine, E; Maurel, A; Brun, M D; Chauvin, F F; Feuilhade de Chauvin, F; Oulid-Aissa, D; Hille, D

1997-06-01

Fluid retention is a phenomenon associated with taxoids. The principal objective of this study was to investigate the pathophysiological mechanism of docetaxel-induced fluid retention in advanced cancer patients. Docetaxel was administered as a 1 h intravenous infusion every 3 weeks, for at least 4-6 consecutive cycles, to patients with advanced breast (n = 21) or ovarian (n = 3) carcinoma, who had received previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 day before docetaxel infusion, significantly reduces the incidence and severity of fluid retention. This prophylactic corticosteroid regimen is currently recommended for patients receiving docetaxel but was not permitted in this study because of its possible interference with the underlying pathophysiology of the fluid retention. Fluid retention occurred in 21 of the 24 patients but was mainly mild to moderate, with only five patients experiencing severe fluid retention. Eighteen patients received symptomatic flavonoid treatment, commonly prescribed after the last cycle. Specific investigations for fluid retention confirmed a relationship between cumulative docetaxel dose and development of fluid retention. Capillary filtration test analysis showed a two-step process for fluid retention generation, with progressive congestion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic drainage. A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention.

Acute interstitial edematous pancreatitis: Findings on non-enhanced MR imaging

PubMed Central

Zhang, Xiao-Ming; Feng, Zhi-Song; Zhao, Qiong-Hui; Xiao, Chun-Ming; Mitchell, Donald G; Shu, Jian; Zeng, Nan-Lin; Xu, Xiao-Xue; Lei, Jun-Yang; Tian, Xiao-Bing

2006-01-01

AIM: To study the appearances of acute interstitial edematous pancreatitis (IEP) on non-enhanced MR imaging. METHODS: A total of 53 patients with IEP diagnosed by clinical features and laboratory findings were underwent MR imaging. MR imaging sequences included fast spoiled gradient echo (FSPGR) fat saturation axial T1-weighted imaging, gradient echo T1-weighted (in phase), single shot fast spin echo (SSFSE) T2-weighted, respiratory triggered (R-T) T2-weighted with fat saturation, and MR cholangiopancreatography. Using the MR severity score index, pancreatitis was graded as mild (0-2 points), moderate (3-6 points) and severe (7-10 points). RESULTS: Among the 53 patients, IEP was graded as mild in 37 patients and as moderate in 16 patients. Forty-seven of 53 (89%) patients had at least one abnormality on MR images. Pancreas was hypointense relative to liver on FSPGR T1-weighted images in 18.9% of patients, and hyperintense in 25% and 30% on SSFSE T2-weighted and R-T T2-weighted images, respectively. The prevalences of the findings of IEP on R-T T2-weighted images were, respectively, 85% for pancreatic fascial plane, 77% for left renal fascial plane, 55% for peripancreatic fat stranding, 42% for right renal fascial plane, 45% for perivascular fluid, 40% for thickened pancreatic lobular septum and 25% for peripancreatic fluid, which were markedly higher than those on in-phase or SSFSE T2-weighted images (P < 0.001). CONCLUSION: IEP primarily manifests on non-enhanced MR images as thickened pancreatic fascial plane, left renal fascial plane, peripancreatic fat stranding, and peripancreatic fluid. R-T T2-weighted imaging is more sensitive than in-phase and SSFSE T2-weighted imaging for depicting IEP. PMID:17007053

Inhibition of hyaluronan synthesis in rats reduces renal ability to excrete fluid and electrolytes during acute hydration

PubMed Central

Stridh, Sara; Palm, Fredrik

2013-01-01

Background. Hyaluronan (HA) is the dominant glycosaminoglycan in the renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid handling due to its water-attracting properties and the changes occurring in parallel to acute variations in the body hydration status. Methods. HA production was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45 ± 0.07 g/day/kg body weight) in rats prior to hydration. Results. Following hypotonic hydration for 135 min in control animals, diuresis and osmotic excretion increased while sodium excretion and glomerular filtration rate (GFR) remained unchanged. The medullary and cortical HA contents were 7.85 ± 1.29 ng/mg protein and 0.08 ± 0.01 ng/mg protein, respectively. Medullary HA content after 4-MU was 38% of that in controls (2.98 ± 0.95 ng/g protein, p < 0.05), while the low cortical levels were unaffected. Baseline urine flow was not different from that in controls. The diuretic response to hydration was, however, only 51% of that in controls (157 ± 36 versus 306 ± 54 µl/g kidney weight/135 min, p < 0.05) and the osmolar excretion only 47% of that in controls (174 ± 47 versus 374 ± 41 µOsm/g kidney weight/135 min, p < 0.05). Sodium excretion, GFR, and arterial blood pressure were similar to that in control rats and unaltered during hydration. Conclusions. Reduction of renomedullary interstitial HA using 4-MU reduces the ability of the kidney to respond appropriately upon acute hydration. The results strengthen the concept of renomedullary HA as a modulator of tubular fluid handling by changing the physicochemical properties of the interstitial space. PMID:24102146

Constraints of gas venting activity for the interstitial water geochemistry at the shallow gas hydrate site, eastern margin of the Japan Sea; results from high resolution time-series fluid sampling by OsmoSampler

NASA Astrophysics Data System (ADS)

Owari, S.; Tomaru, H.; Matsumoto, R.

2016-12-01

We have conducted ROV researches in the eastern margin of the Japan Sea where active gas venting and outcropping of gas hydrates were observed near the seafloor and have found the strength and location of venting had changed within a few days. These observations indicate the seafloor environments with the shallow gas hydrate system could have changed for short period compared to a geological time scale. We have applied a long-term osmotic fluid sampling system "OsmoSampler" on the active gas hydrate system for one year in order to document how the gas venting and gas hydrate activity have changed the geochemical environments near the seafloor. All the major ion concentrations in the interstitial water show synchronous increase and decrease repeatedly in three to five days, reflecting the incorporation and release of fresh water in gas hydrates in response to the gas concentration change near the sampling site. Dissolved methane concentration increases rapidly and excessively (over several mM) in the first 40 days corresponding to the active gas venting. The increases of methane concentration are often associated with high ion concentration during high water pressure period, indicating excess gas release from shallow gas pockets. Contrarily, enhanced gas hydrate growth may plug the fluid-gas paths in shallow sediment, reducing gas hydrate formation due to the decrease of methane flux. This study was conducted under the commission from AIST as a part of the methane hydrate research project funded by METI (the Ministry of Economy, Trade and Industry, Japan).

Acute interstitial edematous pancreatitis: Findings on non-enhanced MR imaging.

PubMed

Zhang, Xiao-Ming; Feng, Zhi-Song; Zhao, Qiong-Hui; Xiao, Chun-Ming; Mitchell, Donald-G; Shu, Jian; Zeng, Nan-Lin; Xu, Xiao-Xue; Lei, Jun-Yang; Tian, Xiao-Bing

2006-09-28

To study the appearances of acute interstitial edematous pancreatitis (IEP) on non-enhanced MR imaging. A total of 53 patients with IEP diagnosed by clinical features and laboratory findings were underwent MR imaging. MR imaging sequences included fast spoiled gradient echo (FSPGR) fat saturation axial T1-weighted imaging, gradient echo T1-weighted (in phase), single shot fast spin echo (SSFSE) T2-weighted, respiratory triggered (R-T) T2-weighted with fat saturation, and MR cholangiopancreatography. Using the MR severity score index, pancreatitis was graded as mild (0-2 points), moderate (3-6 points) and severe (7-10 points). Among the 53 patients, IEP was graded as mild in 37 patients and as moderate in 16 patients. Forty-seven of 53 (89%) patients had at least one abnormality on MR images. Pancreas was hypointense relative to liver on FSPGR T1-weighted images in 18.9% of patients, and hyperintense in 25% and 30% on SSFSE T2-weighted and R-T T2-weighted images, respectively. The prevalences of the findings of IEP on R-T T2-weighted images were, respectively, 85% for pancreatic fascial plane, 77% for left renal fascial plane, 55% for peripancreatic fat stranding, 42% for right renal fascial plane, 45% for perivascular fluid, 40% for thickened pancreatic lobular septum and 25% for peripancreatic fluid, which were markedly higher than those on in-phase or SSFSE T2-weighted images (P<0.001). IEP primarily manifests on non-enhanced MR images as thickened pancreatic fascial plane, left renal fascial plane, peripancreatic fat stranding, and peripancreatic fluid. R-T T2-weighted imaging is more sensitive than in-phase and SSFSE T2-weighted imaging for depicting IEP.

Cerebrospinal and Interstitial Fluid Transport via the Glymphatic Pathway Modeled by Optimal Mass Transport

PubMed Central

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-01-01

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4 min over ∼3 hrs in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. PMID:28323163

Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport.

PubMed

Ratner, Vadim; Gao, Yi; Lee, Hedok; Elkin, Rena; Nedergaard, Maiken; Benveniste, Helene; Tannenbaum, Allen

2017-05-15

The glymphatic pathway is a system which facilitates continuous cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange and plays a key role in removing waste products from the rodent brain. Dysfunction of the glymphatic pathway may be implicated in the pathophysiology of Alzheimer's disease. Intriguingly, the glymphatic system is most active during deep wave sleep general anesthesia. By using paramagnetic tracers administered into CSF of rodents, we previously showed the utility of MRI in characterizing a macroscopic whole brain view of glymphatic transport but we have yet to define and visualize the specific flow patterns. Here we have applied an alternative mathematical analysis approach to a dynamic time series of MRI images acquired every 4min over ∼3h in anesthetized rats, following administration of a small molecular weight paramagnetic tracer into the CSF reservoir of the cisterna magna. We use Optimal Mass Transport (OMT) to model the glymphatic flow vector field, and then analyze the flow to find the network of CSF-ISF flow channels. We use 3D visualization computational tools to visualize the OMT defined network of CSF-ISF flow channels in relation to anatomical and vascular key landmarks from the live rodent brain. The resulting OMT model of the glymphatic transport network agrees largely with the current understanding of the glymphatic transport patterns defined by dynamic contrast-enhanced MRI revealing key CSF transport pathways along the ventral surface of the brain with a trajectory towards the pineal gland, cerebellum, hypothalamus and olfactory bulb. In addition, the OMT analysis also revealed some interesting previously unnoticed behaviors regarding CSF transport involving parenchymal streamlines moving from ventral reservoirs towards the surface of the brain, olfactory bulb and large central veins. Copyright © 2017. Published by Elsevier Inc.

Biogeochemistry of Dissolved Free Amino Acids in Marine Sediments.

DTIC Science & Technology

1980-09-01

Oceans , the Black Sea , and the Sea of Azov. Interstitial water of surface sediments | _ A Irom these regions, including even Pacific red clays and...Awapara, 1962; de Zwaan, 1977). Serine has been reported as the major constituent of the ceolomic fluid of a sea urchin (Giordano et al., 1950). The...Harper, and F. P. Filice (1950) The amino acids ot a starfish and a sea urchin (Asteroidea and Echinoidea). Wasmann J. Biol. 8, 129-132. Goldberg, E

High-contrast imaging of mycobacterium tuberculosis using third-harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Kim, Bo Ram; Lee, Eungjang; Park, Seung-Han

2015-07-01

Nonlinear optical microcopy has become an important tool in investigating biomaterials due to its various advantages such as label-free imaging capabilities. In particular, it has been shown that third-harmonic generation (THG) signals can be produced at interfaces between an aqueous medium (e.g. cytoplasm, interstitial fluid) and a mineralized lipidic surface. In this work, we have demonstrated that label-free high-contrast THG images of the mycobacterium tuberculosis can be obtained using THG microscopy.

Effect of microvascular distribution and its density on interstitial fluid pressure in solid tumors: A computational model.

PubMed

Mohammadi, M; Chen, P

2015-09-01

Solid tumors with different microvascular densities (MVD) have been shown to have different outcomes in clinical studies. Other studies have demonstrated the significant correlation between high MVD, elevated interstitial fluid pressure (IFP) and metastasis in cancers. Elevated IFP in solid tumors prevents drug macromolecules reaching most cancerous cells. To overcome this barrier, antiangiogenesis drugs can reduce MVD within the tumor and lower IFP. A quantitative approach is essential to compute how much reduction in MVD is required for a specific tumor to reach a desired amount of IFP for drug delivery purposes. Here we provide a computational framework to investigate how IFP is affected by the tumor size, the MVD, and location of vessels within the tumor. A general physiologically relevant tumor type with a heterogenous vascular structure surrounded by normal tissue is utilized. Then the continuity equation, Darcy's law, and Starling's equation are applied in the continuum mechanics model, which can calculate IFP for different cases of solid tumors. High MVD causes IFP elevation in solid tumors, and IFP distribution correlates with microvascular distribution within tumor tissue. However, for tumors with constant MVD but different microvascular structures, the average values of IFP were found to be the same. Moreover, for a constant MVD and vascular distribution, an increase in tumor size leads to increased IFP. Copyright © 2015 Elsevier Inc. All rights reserved.

Delivery of platinum(IV) drug to subcutaneous tumor and lung metastasis using bradykinin-potentiating peptide-decorated chitosan nanoparticles.

PubMed

Wang, Xin; Yang, Chenchen; Zhang, Yajun; Zhen, Xu; Wu, Wei; Jiang, Xiqun

2014-08-01

Selectively activating tumor vessels to increase drug delivery and reduce interstitial fluid pressure of tumors is actively pursued. Here we developed a vasoactive peptide-decorated chitosan nanoparticles for enhancing drug accumulation and penetration in subcutaneous tumor and lung metastasis. The vasoactive peptide used here is bradykinin-potentiating peptide (BPP) containing 9 amino acid residues and the drug is bioreductively sensitive platinum(IV) compound which becomes cisplatin in intracellular reductive environments. Both peptide and drug are covalently linked with chitosan nanoparticles with a diameter of 120 nm. We demonstrate that BPP-decorated chitosan nanoparticles increase the tumorous vascular permeability and reduce the interstitial fluid pressure of tumor simultaneously, both of which improve the penetration of nanoparticles in tumor tissues. The in vivo biodistribution and tumor inhibition examinations demonstrate that the BPP-decorated nanoparticle formulation has more superior efficacy in enhancing drug accumulation in tumor, restraining tumor growth and prolonging the lifetime of tumor-bearing mice than free drug and non-decorated nanoparticle formulation. Meanwhile, the drug accumulation in the lung with metastasis reaches 17% and 20% injected dose per gram of lung for the chitosan nanoparticles without and with BPP decoration, respectively, which is 10-fold larger than that of free cisplatin. The examination of lung metastasis inhibition further indicates that BPP-decorated chitosan nanoparticle formulations can more effectively inhibit lung metastasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Sulfide-associated mineral assemblages in the Bushveld Complex, South Africa: platinum-group element enrichment by vapor refining by chloride-carbonate fluids

NASA Astrophysics Data System (ADS)

Kanitpanyacharoen, W.; Boudreau, A. E.

2013-02-01

The petrology of base metal sulfides and associated accessory minerals in rocks away from economically significant ore zones such as the Merensky Reef of the Bushveld Complex has previously received only scant attention, yet this information is critical in the evaluation of models for the formation of Bushveld-type platinum-group element (PGE) deposits. Trace sulfide minerals, primarily pyrite, pyrrhotite, pentlandite, and chalcopyrite are generally less than 100 microns in size, and occur as disseminated interstitial individual grains, as polyphase assemblages, and less commonly as inclusions in pyroxene, plagioclase, and olivine. Pyrite after pyrrhotite is commonly associated with low temperature greenschist alteration haloes around sulfide grains. Pyrrhotite hosted by Cr- and Ti-poor magnetite (Fe3O4) occurs in several samples from the Marginal to Lower Critical Zones below the platiniferous Merensky Reef. These grains occur with calcite that is in textural equilibrium with the igneous silicate minerals, occur with Cl-rich apatite, and are interpreted as resulting from high temperature sulfur loss during degassing of interstitial liquid. A quantitative model demonstrates how many of the first-order features of the Bushveld ore metal distribution could have developed by vapor refining of the crystal pile by chloride-carbonate-rich fluids during which sulfur and sulfide are continuously recycled, with sulfur moving from the interior of the crystal pile to the top during vapor degassing.

Simulation of Complex Transport of Nanoparticles around a Tumor Using Tumor-Microenvironment-on-Chip

PubMed Central

Kwak, Bongseop; Ozcelikkale, Altug; Shin, Crystal S.; Park, Kinam; Han, Bumsoo

2014-01-01

Delivery of therapeutic agents selectively to tumor tissue, which is referred as “targeted delivery,” is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment. PMID:25194778

Interstitial water studies on small core samples, Deep Sea Drilling Project, Leg 8

USGS Publications Warehouse

Manheim, F.T.; Sayles, F.L.

1971-01-01

Leg 8 sites are dominated by siliceous-calcareous biogenic oozes having depositional rates of 0.1 to 1.5 cm/1000 years. Conservative constituents of pore fluids showed, as have cores from other pelagic areas of the Pacific, insignificant or marginally significant changes with depth and location. However, in Sites 70 and 71, calcium, magnesium and strontium showed major shifts in concentration with depth. These changes appear to be related to recrystallization phenomena in skeletal debris of nannoplankton and to the relative accumulation rate of the sediments. The chemical anomalies increase relatively smoothly with depth, demonstrating the effectiveness of vertical diffusional communication, and apparent lack of bulk fluid movement, as noted in Leg 7 and other sites.

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models

PubMed Central

2014-01-01

Background Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Methods Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. Results An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Conclusions Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route. PMID:24684892

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models.

PubMed

Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

2014-04-01

Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.

Nanoscale Structure at Mineral-Fluid Interfaces

NASA Astrophysics Data System (ADS)

Sturchio, N. C.; Sturchio, N. C.; Fenter, P.; Cheng, L.; Park, C.; Zhang, Z.; Zhang, Z.; Nagy, K. L.; Schlegel, M. L.

2001-12-01

The nature of nanoparticles and their role in the natural environment is currently a subject of renewed interest. The high surface area (and surface area-to-volume ratio) of nanoparticles exerts a widespread influence on geochemical reactions and transport processes. A thorough understanding of the nanoscale world remains largely hypothetical, however, because of the challenges associated with characterizing nanoscale structures and processes. Recent insights gained from high-resolution synchrotron x-ray reflectivity measurements at the solid-fluid interfaces of macroscopic (i.e., mm-scale) mineral particles may provide relevant guidelines for expected nanoparticle surface structures. For example, at calcite-water and barite-water interfaces, undercoordinated surface cations bond with water species of variable protonation, and modest relaxations (to several hundredths of a nanometer) affect the outermost unit cells [1,2]. Undercoordinated tetrahedral ions at aluminosilicate surfaces also bond with water species, whereas interstitial or interlayer alkali or alkaline earth ions at the surface may readily exchange with hydronium or other ions; modest relaxations also affect the outermost unit cells [3,4]. Modulation of liquid water structure out to about one nanometer has been observed at the (001) cleavage surface of muscovite in deionized water, and may be present at other mineral-fluid interfaces [4]. Dissolution mechanisms at the orthoclase-water interface have been clarified by combining x-ray reflectivity and scanning force microscopy measurements [5]. Further progress in understanding nanoscale structures and processes at macroscopic mineral-water interfaces is likely to benefit nanoparticle studies. [1] Fenter et al. (2000) Geochim. Cosmochim. Acta 64, 1221-1228. [2] Fenter et al. (2001) J. Phys. Chem. B 105(34), 8112-8119. [3] Fenter et al. (2000) Geochim. Cosmochim. Acta 64, 3663-3673. [4] Cheng et al. (2001) Phys. Rev. Lett., (in press). [5] Teng et al. (2001) Geochim. Cosmochim. Acta 65, (in press).

Gastroesophageal reflux and lung disease.

PubMed

Meyer, Keith C

2015-08-01

Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

Dithiobis(succinimidyl propionate) modified gold microarray electrode based electrochemical immunosensor for ultrasensitive detection of cortisol.

PubMed

Arya, Sunil K; Chornokur, Ganna; Venugopal, Manju; Bhansali, Shekhar

2010-06-15

Gold microelectrode arrays functionalized with dithiobis(succinimidyl propionate) self-assembled monolayer (SAM) have been used to fabricate an ultrasensitive, disposable, electrochemical cortisol immunosensor. Cortisol specific monoclonal antibody (C-Mab) was covalently immobilized on the surface of gold microelectrode array and the sensors were exposed to solutions with different cortisol concentration. After C-Mab binding, unreacted active groups of DTSP were blocked using ethanol amine (EA) and label-free electrochemical impedance (EIS) technique was used to determine cortisol concentration. EIS results confirmed that EA/C-Mab/DTSP/Au based biosensor can accurately detect cortisol in the range of 1pM-100nM. The biosensor was successfully used for the measurement of cortisol in interstitial fluid in vitro. This research establishes the feasibility of using impedance based biosensor architecture for disposable, wearable cortisol detector. Copyright 2010 Elsevier B.V. All rights reserved.

Impact of Interstitial Ni on the Thermoelectric Properties of the Half-Heusler TiNiSn.

PubMed

Barczak, Sonia A; Buckman, Jim; Smith, Ronald I; Baker, Annabelle R; Don, Eric; Forbes, Ian; Bos, Jan-Willem G

2018-03-30

TiNiSn is an intensively studied half-Heusler alloy that shows great potential for waste heat recovery. Here, we report on the structures and thermoelectric properties of a series of metal-rich TiNi 1+y Sn compositions prepared via solid-state reactions and hot pressing. A general relation between the amount of interstitial Ni and lattice parameter is determined from neutron powder diffraction. High-resolution synchrotron X-ray powder diffraction reveals the occurrence of strain broadening upon hot pressing, which is attributed to the metastable arrangement of interstitial Ni. Hall measurements confirm that interstitial Ni causes weak n-type doping and a reduction in carrier mobility, which limits the power factor to 2.5-3 mW m -1 K -2 for these samples. The thermal conductivity was modelled within the Callaway approximation and is quantitively linked to the amount of interstitial Ni, resulting in a predicted value of 12.7 W m -1 K -1 at 323 K for stoichiometric TiNiSn. Interstitial Ni leads to a reduction of the thermal band gap and moves the peak ZT = 0.4 to lower temperatures, thus offering the possibility to engineer a broad ZT plateau. This work adds further insight into the impact of small amounts of interstitial Ni on the thermal and electrical transport of TiNiSn.

Impact of Interstitial Ni on the Thermoelectric Properties of the Half-Heusler TiNiSn

PubMed Central

Barczak, Sonia A.; Smith, Ronald I.; Baker, Annabelle R.; Don, Eric; Forbes, Ian

2018-01-01

TiNiSn is an intensively studied half-Heusler alloy that shows great potential for waste heat recovery. Here, we report on the structures and thermoelectric properties of a series of metal-rich TiNi1+ySn compositions prepared via solid-state reactions and hot pressing. A general relation between the amount of interstitial Ni and lattice parameter is determined from neutron powder diffraction. High-resolution synchrotron X-ray powder diffraction reveals the occurrence of strain broadening upon hot pressing, which is attributed to the metastable arrangement of interstitial Ni. Hall measurements confirm that interstitial Ni causes weak n-type doping and a reduction in carrier mobility, which limits the power factor to 2.5–3 mW m−1 K−2 for these samples. The thermal conductivity was modelled within the Callaway approximation and is quantitively linked to the amount of interstitial Ni, resulting in a predicted value of 12.7 W m−1 K−1 at 323 K for stoichiometric TiNiSn. Interstitial Ni leads to a reduction of the thermal band gap and moves the peak ZT = 0.4 to lower temperatures, thus offering the possibility to engineer a broad ZT plateau. This work adds further insight into the impact of small amounts of interstitial Ni on the thermal and electrical transport of TiNiSn. PMID:29601547

Osmosis and solute-solvent drag: fluid transport and fluid exchange in animals and plants.

PubMed

Hammel, H T; Schlegel, Whitney M

2005-01-01

In 1903, George Hulett explained how solute alters water in an aqueous solution to lower the vapor pressure of its water. Hulett also explained how the same altered water causes osmosis and osmotic pressure when the solution is separated from liquid water by a membrane permeable to the water only. Hulett recognized that the solute molecules diffuse toward all boundaries of the solution containing the solute. Solute diffusion is stopped at all boundaries, at an open-unopposed surface of the solution, at a semipermeable membrane, at a container wall, or at the boundary of a solid or gaseous inclusion surrounded by solution but not dissolved in it. At each boundary of the solution, the solute molecules are reflected, they change momentum, and the change of momentum of all reflected molecules is a pressure, a solute pressure (i.e., a force on a unit area of reflecting boundary). When a boundary of the solution is open and unopposed, the solute pressure alters the internal tension in the force bonding the water in its liquid phase, namely, the hydrogen bond. All altered properties of the water in the solution are explained by the altered internal tension of the water in the solution. We acclaim Hulett's explanation of osmosis, osmotic pressure, and lowering of the vapor pressure of water in an aqueous solution. His explanation is self-evident. It is the necessary, sufficient, and inescapable explanation of all altered properties of the water in the solution relative to the same property of pure liquid water at the same externally applied pressure and the same temperature. We extend Hulett's explanation of osmosis to include the osmotic effects of solute diffusing through solvent and dragging on the solvent through which it diffuses. Therein lies the explanations of (1) the extravasation from and return of interstitial fluid to capillaries, (2) the return of luminal fluid in the proximal and distal convoluted tubules of a kidney nephron to their peritubular capillaries, (3) the return of interstitial fluid to the vasa recta, (4) return of aqueous humor to the episcleral veins, and (5) flow of phloem from source to sink in higher plants and many more examples of fluid transport and fluid exchange in animal and plant physiology. When a membrane is permeable to water only and when it separates differing aqueous solutions, the flow of water is from the solution with the lower osmotic pressure to the solution with the higher osmotic pressure.

Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

PubMed

Chang, Ronald; Holcomb, John B

2016-07-01

Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis.

A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.

PubMed

Saito, Yoshinobu; Nagayama, Mikie; Miura, Yukiko; Ogushi, Satoko; Suzuki, Yasutomo; Noro, Rintaro; Minegishi, Yuji; Kimura, Go; Kondo, Yukihiro; Gemma, Akihiko

2013-05-01

A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

NASA Technical Reports Server (NTRS)

Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

1992-01-01

The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

Molecular Genetic Studies of Bone Mechanical Strain and of Pedigrees with Very High Bone Density

DTIC Science & Technology

2005-06-01

remodelling. J Biomech, 20:1083-1093. 2. Hillsley MV, and Frangos , JA 1994 Bone tissue engineering: the role of interstitial fluid flow. Biotech Bioeng, 43...However, the nature of interaction between other pathways remains to be determined. References: 1. Hillsley MV, and Frangos , JA (1994) Bone tissue...termination 2. Hillsley, M. V., and Frangos , J. A. (1994) Biotechnol. Bioeng. 43, 573-581 of the IGF-I signaling pathway (16-22). Accordingly, we pos- 3. Kapur

Sonophoresis for Rapid Assessment of Interstitial Fluid and Drug Delivery

DTIC Science & Technology

2007-10-01

sensitive indicator of local diseases, for example skin cancer, psoriasis and eczema , but also of certain systemic diseases such as cardiovascular disease...cytokine " functionality -map" that precisely represents skin’s specific diseased milieu (Fig. 2b-CI and Fig. 3a-AD and PS, 3 additional data in. Supp...yielded a unique cytokine " functionality map", which correlates with the specific diseased state (figure 2d and 3a). A striking, rapid upregulation was

Fluid-Structure Model of Lymphatic Valve and Vessel

NASA Astrophysics Data System (ADS)

Wolf, Ki; Ballard, Matthew; Nepiyushchikh, Zhanna; Razavi, Mohammad; Dixon, Brandon; Alexeev, Alexander

The lymphatic system is a part of the circulatory system that performs a range of important functions such as transportation of interstitial fluid, fatty acid, and immune cells. The lymphatic vessels are composed of contractile walls to pump lymph against adverse pressure gradient and lymphatic valves that prevent back flow. Despite the importance of lymphatic system, the contribution of mechanical and geometric changes of lymphatic valves and vessels in pathologies of lymphatic dysfunction, such as lymphedema, is not well understood. We developed a coupled fluid-solid computational model to simultaneously simulate a lymphatic vessel, valve, and flow. A lattice Boltzmann model is used to represent the fluid component, while lattice spring model is used for the solid component of the lymphatic vessel, whose mechanical properties are derived experimentally. Behaviors such as lymph flow pattern and lymphatic valve performance against backflow and adverse pressure gradient under varied parameters of lymphatic valve and vessel geometry and mechanical properties are investigated to provide a better insight into the dynamics of lymphatic vessels, valves, and system and give insight into how they might fail in disease. NSF CMMI-1635133.

Presumed lupus erythematosus cells identified in bronchoalveolar lavage fluid from a Mexican Hairless dog.

PubMed

Black, Laura J; Hechler, Ashley C; Duffy, Maura E; Beatty, Sarah S K

2017-06-01

A neutered male Mexican Hairless dog was presented for generalized weight loss and weakness. Initial laboratory testing and diagnostic imaging revealed thrombocytopenia and an interstitial to miliary lung pattern affecting all lung fields. Mild joint effusion was found on physical examination affecting the stifle, tarsal, carpal, and elbow joints. Examination of synovial fluid demonstrated an inflammatory polyarthropathy in 3 joints. Cytocentrifuged and direct preparations of the bronchoalveolar lavage (BAL) fluid sample were made and cells consistent with lupus erythematosus (LE) cells and ragocytes were found. Based on these findings, the anti-nuclear antibody (ANA) titer was determined as 1:640. A clinical diagnosis of systemic LE was made based on the satisfaction of 2 major criteria (thrombocytopenia and inflammatory polyarthritis), 4 minor criteria (central nervous system signs, lymphadenopathy, fever of unknown origin, and pleuritis), positive ANA titer, and the identification of presumed LE cells in BAL fluid. This case report highlights a novel finding of LE cells in respiratory secretions and provides a review of diagnostic criteria of systemic LE. © 2017 American Society for Veterinary Clinical Pathology.

Contributions of oxygen vacancies and titanium interstitials to band-gap states of reduced titania

NASA Astrophysics Data System (ADS)

Li, Jingfeng; Lazzari, Rémi; Chenot, Stéphane; Jupille, Jacques

2018-01-01

The spectroscopic fingerprints of the point defects of titanium dioxide remain highly controversial. Seemingly indisputable experiments lead to conflicting conclusions in which oxygen vacancies and titanium interstitials are alternately referred to as the primary origin of the Ti 3 d band-gap states. We report on experiments performed by electron energy loss spectroscopy whose key is the direct annealing of only the very surface of rutile TiO2(110 ) crystals and the simultaneous measurement of its temperature via the Bose-Einstein loss/gain ratio. By surface preparations involving reactions with oxygen and water vapor, in particular, under electron irradiation, vacancy- and interstitial-related band-gap states are singled out. Off-specular measurements reveal that both types of defects contribute to a unique charge distribution that peaks in subsurface layers with a common dispersive behavior.

Magneto-vibratory separation of glass and bronze granular mixtures immersed in a paramagnetic liquid.

PubMed

López-Alcaraz, P; Catherall, A T; Hill, R J A; Leaper, M C; Swift, Michael R; King, P J

2007-10-01

A fluid-immersed granular mixture may spontaneously separate when subjected to vertical vibration, separation occurring when the ratio of particle inertia to fluid drag is sufficiently different between the component species of the mixture. Here, we describe how fluid-driven separation is influenced by magneto-Archimedes buoyancy, the additional buoyancy force experienced by a body immersed in a paramagnetic fluid when a strong inhomogeneous magnetic field is applied. In our experiments glass and bronze mixtures immersed in paramagnetic aqueous solutions of MnCl2 have been subjected to sinusoidal vertical vibration. In the absence of a magnetic field the separation is similar to that observed when the interstitial fluid is water. However, at modest applied magnetic fields, magneto-Archimedes buoyancy may balance the inertia/fluid-drag separation mechanism, or it may dominate the separation process. We identify the vibratory and magnetic conditions for four granular configurations, each having distinctive granular convection. Abrupt transitions between these states occur at well-defined values of the magnetic and vibrational parameters. In order to gain insight into the dynamics of the separation process we use computer simulations based on solutions of the Navier-Stokes' equations. The simulations reproduce the experimental results revealing the important role of convection and gap formation in the stability of the different states.

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

Jena, Puru; Kandalam, Anil K.; Christian, Theresa M.

Gallium phosphide bismide (GaP1-xBix) epilayers with bismuth fractions from 0.9% to 3.2%, as calculated from lattice parameter measurements, were studied with Rutherford backscattering spectrometry (RBS) to directly measure bismuth incorporation. The total bismuth fractions found by RBS were higher than expected from the lattice parameter calculations. Furthermore, in one analyzed sample grown by molecular beam epitaxy at 300 degrees C, 55% of incorporated bismuth was found to occupy interstitial sites. We discuss implications of this high interstitial incorporation fraction and its possible relationship to x-ray diffraction and photoluminescence measurements of GaP0.99Bi0.01.

Chronic effect of cadmium in sediments on colonization by benthic marine organisms: An evaluation of the role of interstitial cadmium and acid-volatile sulfide in biological availability

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

Hansen, D.J.; Berry, W.J.; Benyi, S.J.

1996-12-01

The role of interstitial cadmium and acid-volatile sulfide (AVS) in controlling the bioavailability of sediment-associated metal was examined using the chronic saltwater benthic colonization test. Sediments were spiked to achieve nominal cadmium/AVS molar ratios of 0.0 (control), 0.1, 0.8, and 3.0 in this 118-d test. Oxidation of AVS in the surficial 2.4 cm within 2 to 4 weeks resulted in sulfide profiles similar to those occurring naturally in local sediments. In the nominal 0.1 cadmium/AVS treatment measured simultaneously extracted metal (SEM{sub Cd}) was always less than AVS. Interstitial cadmium concentrations were less than those likely to cause biological effects. Nomore » significant biological effects were detected. In the nominal 0.8 cadmium/AVS treatment, measured SEM{sub Cd} commonly exceeded AVS in the surficial 2.4 cm of sediment. Interstitial cadmium concentrations were of likely toxicological significance to highly sensitive species. Shifts in the presence or absence over all taxa, and fewer macrobenthic polychaetes (Mediomastus ambiseta, Streblospio benedicti, and Podarke obscurea) and unidentified meiofaunal nematodes, were observed. In the nominal 3.0 cadmium/AVS treatment, concentrations of SEM{sub Cd} were always greater than AVS throughout the sediment column. Interstitial cadmium ranged from 28,000 to 174,000 {micro}g/L. In addition to the effects above, the sediments were colonized by fewer macrobenthic species, polychaete species, and harpacticoids; had lower densities of diatoms; lacked bivalve molluscs; and exhibited other impacts. Over all treatments, the observed biological responses were consistent with SEM{sub Cd}/AVS ratios in surficial sediments and interstitial water cadmium concentrations.« less

Increasing minority carrier lifetime in as-grown multicrystalline silicon by low temperature internal gettering

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

Al-Amin, M., E-mail: m.al-amin@warwick.ac.uk; Murphy, J. D., E-mail: john.d.murphy@warwick.ac.uk

2016-06-21

We report a systematic study into the effects of long low temperature (≤500 °C) annealing on the lifetime and interstitial iron distributions in as-grown multicrystalline silicon (mc-Si) from different ingot height positions. Samples are characterised in terms of dislocation density, and lifetime and interstitial iron concentration measurements are made at every stage using a temporary room temperature iodine-ethanol surface passivation scheme. Our measurement procedure allows these properties to be monitored during processing in a pseudo in situ way. Sufficient annealing at 300 °C and 400 °C increases lifetime in all cases studied, and annealing at 500 °C was only found to improve relatively poormore » wafers from the top and bottom of the block. We demonstrate that lifetime in poor as-grown wafers can be improved substantially by a low cost process in the absence of any bulk passivation which might result from a dielectric surface film. Substantial improvements are found in bottom wafers, for which annealing at 400 °C for 35 h increases lifetime from 5.5 μs to 38.7 μs. The lifetime of top wafers is improved from 12.1 μs to 23.8 μs under the same conditions. A correlation between interstitial iron concentration reduction and lifetime improvement is found in these cases. Surprisingly, although the interstitial iron concentration exceeds the expected solubility values, low temperature annealing seems to result in an initial increase in interstitial iron concentration, and any subsequent decay is a complex process driven not only by diffusion of interstitial iron.« less

Pneumocystis jirovecii infection in patients with acute interstitial pneumonia.

PubMed

Martínez-Rísquez, M T; Friaza, V; de la Horra, C; Martín-Juan, J; Calderón, E J; Medrano, F J

2018-06-08

Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery.

PubMed

Dolor, Aaron; Szoka, Francis C

2018-06-04

Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies, and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion 2-10-fold. This modest improvement resulted in decreased tumor growth, but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published in vitro and in vivo benefits and limitations of collagenase treatment to improve drug delivery.

The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication

PubMed Central

Béhar, A.; Pujade-Lauraine, E.; Maurel, A.; Brun, M. D.; Lagrue, G.; Feuilhade De Chauvin, F.; Oulid-Aissa, D.; Hille, D.

1997-01-01

Aims Fluid retention is a phenomenon associated with taxoids. The principal objective of this study was to investigate the pathophysiological mechanism of docetaxel-induced fluid retention in advanced cancer patients. Methods Docetaxel was administered as a 1 h intravenous infusion every 3 weeks, for at least 4–6 consecutive cycles, to patients with advanced breast (n=21) or ovarian (n=3) carcinoma, who had received previous chemotherapy, 21 for advanced disease. Phase II clinical trials have shown that 5 day corticosteroid comedication, starting 1 day before docetaxel infusion, significantly reduces the incidence and severity of fluid retention. This prophylactic corticosteroid regimen is currently recommended for patients receiving docetaxel but was not permitted in this study because of its possible interference with the underlying pathophysiology of the fluid retention. Results Fluid retention occurred in 21 of the 24 patients but was mainly mild to moderate, with only five patients experiencing severe fluid retention. Eighteen patients received symptomatic flavonoid treatment, commonly prescribed after the last cycle. Specific investigations for fluid retention confirmed a relationship between cumulative docetaxel dose and development of fluid retention. Capillary filtration test analysis showed a two-step process for fluid retention generation, with progressive congestion of the interstitial space by proteins and water starting between the second and the fourth cycle, followed by insufficient lymphatic drainage. Conclusions A vascular protector such as micronized diosmine hesperidine with recommended corticosteroid premedication and benzopyrones may be useful in preventing and treating docetaxel-induced fluid retention. PMID:9205828

The role of brain barriers in fluid movement in the CNS: is there a 'glymphatic' system?

PubMed

Abbott, N Joan; Pizzo, Michelle E; Preston, Jane E; Janigro, Damir; Thorne, Robert G

2018-03-01

Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

Cardiovascular response to lower body negative pressure stimulation before, during, and after space flight

NASA Technical Reports Server (NTRS)

Baisch, F.; Beck, L.; Blomqvist, G.; Wolfram, G.; Drescher, J.; Rome, J. L.; Drummer, C.

2000-01-01

BACKGROUND: It is well known that space travel cause post-flight orthostatic hypotension and it was assumed that autonomic cardiovascular control deteriorates in space. Lower body negative pressure (LBNP) was used to assess autonomic function of the cardiovascular system. METHODS: LBNP tests were performed on six crew-members before and on the first days post-flight in a series of three space missions. Additionally, two of the subjects performed LBNP tests in-flight. LBNP mimics fluid distribution of upright posture in a gravity independent way. It causes an artificial sequestration of blood, reduces preload, and filtrates plasma into the lower part of the body. Fluid distribution was assessed by bioelectrical impedance and anthropometric measurements. RESULTS: Heart rate, blood pressure, and total peripheral resistance increased significantly during LBNP experiments in-flight. The decrease in stroke volume, the increased pooling of blood, and the increased filtration of plasma into the lower limbs during LBNP indicated that a plasma volume reduction and a deficit of the interstitial volume of lower limbs rather than a change in cardiovascular control was responsible for the in-flight response. Post-flight LBNP showed no signs of cardiovascular deterioration. The still more pronounced haemodynamic changes during LBNP reflected the expected behaviour of cardiovascular control faced with less intravascular volume. In-flight, the status of an intra-and extravascular fluid deficit increases sympathetic activity, the release of vasoactive substances and consequently blood pressure. Post-flight, blood pressure decreases significantly below pre-flight values after restoration of volume deficits. CONCLUSION: We conclude that the cardiovascular changes in-flight are a consequence of a fluid deficit rather than a consequence of changes in autonomic signal processing.

Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

PubMed Central

Scallan, Joshua P; Davis, Michael J; Huxley, Virginia H

2013-01-01

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 nm) would likewise elevate lymphatic permeability (Ps) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic Ps to rat serum albumin increased by 2.0 ± 0.4-fold (P= 0.01, n= 7) and 2.7 ± 0.8-fold (P= 0.07, n= 7) with ANP and BNP, respectively. In addition to measuring Ps responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo. Notably, ANP abolished spontaneous contraction amplitude (P= 0.005) and frequency (P= 0.006), while BNP augmented both parameters by ∼2-fold (P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries, and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion. PMID:23897233

A 3D Culture Model to Study How Fluid Pressure and Flow Affect the Behavior of Aggregates of Epithelial Cells.

PubMed

Piotrowski-Daspit, Alexandra S; Simi, Allison K; Pang, Mei-Fong; Tien, Joe; Nelson, Celeste M

2017-01-01

Cells are surrounded by mechanical stimuli in their microenvironment. It is important to determine how cells respond to the mechanical information that surrounds them in order to understand both development and disease progression, as well as to be able to predict cell behavior in response to physical stimuli. Here we describe a protocol to determine the effects of interstitial fluid flow on the migratory behavior of an aggregate of epithelial cells in a three-dimensional (3D) culture model. This protocol includes detailed methods for the fabrication of a 3D cell culture chamber with hydrostatic pressure control, the culture of epithelial cells as an aggregate in a collagen gel, and the analysis of collective cell behavior in response to pressure-driven flow.

[Experience in the treatment of interstitial cystitis: review of 17 cases].

PubMed

Flores-Carreras, Oscar; Martínez-Espinoza, Claudia J; González-Ruiz, María Isabel

2011-03-01

The Interstitial Cystitis (IC) has been considered in the past an uncommon pathology, however it has received a special attention during the last 20 years, (1678 scientific articles published since 1984 to 2009). There are many therapeutic options not at all satisfactory because there isn't consensus about diagnostic and treatment. To share our experiences in the treatment of interstitial cystitis, additionally, to comment on the therapeutic response of treatment used. Observational, retrospective an analytic study of 17 treated patients from 22 with diagnosis of IC and Bladder Painful Syndrome (IC/BPS) were managed in Urodifem de Occidente, S.C. a private Urogynecologic unit between January 2001 and April 2010. The diagnosis was done in agreement with the concepts of Interstitial Cystitis group from clinical and cystoscopic characteristics. The treatment was: Dimethyl sulfoxide (DIMSO) and Pentosan Polysulfate. The evaluation was measured by Interstitial Cystitis Symptomatic Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) both validated evaluation instruments, 82% of the patients had a significative improvement of symptomatology and quality of live The ICSI pre and post treatment was of 17.0 and 4.5 and the ICPI was of 14.8 and 4.1 respectively. We recommend the use of combine treatment of DIMSO and PPS in cases of I.C.

020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report

PubMed Central

Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas

2015-01-01

Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).

Resuscitation of severe but brief haemorrhagic shock with PFC in rabbits restores skeletal muscle oxygen delivery and does not alter skeletal muscle metabolism.

PubMed

Audonnet-Blaise, Sandra; Krafft, Marie-Pierre; Smani, Younes; Mertes, Paul-Michel; Marie, Pierre-Yves; Labrude, Pierre; Longrois, Dan; Menu, Patrick

2006-07-01

Studies have demonstrated that perfluorocarbon (PFC) emulsions associated with hyperoxia improved whole body oxygen delivery during resuscitation of acute haemorrhagic shock (HS). Nevertheless the microcirculatory effects of PFC and the potential deleterious effects of hyperoxic reperfusion are still of concern. We investigated (i) the ability of a newly formulated, small sized and highly stable PFC emulsion to increase skeletal muscle oxygen delivery and (ii) the effect of hyperoxic reperfusion on skeletal muscle metabolism after a brief period of ischaemia using an original, microdialysis-based method that allowed simultaneous measurement tissue oxygen pressure (PtiO2) and interstitial lactate and pyruvate. These measurements were carried out in anaesthetised and ventilated (FiO2 = 1) rabbits subjected to acute HS (50% of blood volume withdrawal) and either resuscitated with a PFC emulsion diluted with a 5% albumin solution (16.2 g PFC per kg body weight) (n = 10) or with a modified fluid gelatin solution (Gelofusine) (n = 10). We found no difference between the two groups for the haemodynamic and haematological variables (except for the venous oxygen partial pressure). However, a significant difference was observed in the slope of the regression linear relationship exhibited between the mean arterial pressure (MAP) and the PtiO2, PFC group showing a much steeper slope than Gelofusine group. In addition, PtiO2 values increased linearly with decreasing haematocrit (Hct) values in PFC-resuscitated animals and decreased linearly with decreasing Hct values in Gelofusine-resuscitated animals. There were no differences between the two groups concerning the blood and interstitial lactate/pyruvate ratios suggesting no deleterious effect of hyperoxic resuscitation in skeletal muscle. In conclusion these results suggest that resuscitation of severe, but brief, HS with PFC increased skeletal muscle oxygen delivery without measurable deleterious effects.

The role of interstitial binding in radiation induced segregation in W-Re alloys

NASA Astrophysics Data System (ADS)

Gharaee, Leili; Marian, Jaime; Erhart, Paul

2016-07-01

Due to their high strength and advantageous high-temperature properties, tungsten-based alloys are being considered as plasma-facing candidate materials in fusion devices. Under neutron irradiation, rhenium, which is produced by nuclear transmutation, has been found to precipitate in elongated precipitates forming thermodynamic intermetallic phases at concentrations well below the solubility limit. Recent measurements have shown that Re precipitation can lead to substantial hardening, which may have a detrimental effect on the fracture toughness of W alloys. This puzzle of sub-solubility precipitation points to the role played by irradiation induced defects, specifically mixed solute-W interstitials. Here, using first-principles calculations based on density functional theory, we study the energetics of mixed interstitial defects in W-Re, W-V, and W-Ti alloys, as well as the heat of mixing for each substitutional solute. We find that mixed interstitials in all systems are strongly attracted to each other with binding energies of -2.4 to -3.2 eV and form interstitial pairs that are aligned along parallel first-neighbor <111 > strings. Low barriers for defect translation and rotation enable defect agglomeration and alignment even at moderate temperatures. We propose that these elongated agglomerates of mixed-interstitials may act as precursors for the formation of needle-shaped intermetallic precipitates. This interstitial-based mechanism is not limited to radiation induced segregation and precipitation in W-Re alloys but is also applicable to other body-centered cubic alloys.

Effect of depletion of interstitial hyaluronan on hydraulic conductance in rabbit knee synovium

PubMed Central

Coleman, P J; Scott, D; Abiona, A; Ashhurst, D E; Mason, R M; Levick, J R

1998-01-01

The hydraulic resistance of the synovial lining to fluid outflow from a joint cavity () is important for the retention of intra-articular lubricant. The resistance has been attributed in part to extracellular glycosaminoglycans, including hyaluronan and chondroitin sulphates. Increased permeability in joints infused with testicular hyaluronidase, which digests both chondroitin sulphates and hyaluronan, supports this view. In this study the importance of interstitial hyaluronan per se was assessed using leech and Streptomyces hyaluronidases, which degrade only hyaluronan. Ringer solution was infused into the knee joint cavity of anaesthetized rabbits for 30 min, with or without hyaluronidase, after which intra-articular pressure (Pj) was raised and the relation between pressure and outflow determined. Treatment with Streptomyces, leech or testicular hyaluronidases increased the fluid escape rates by similar factors, namely 4- to 6-fold. After Streptomyces hyaluronidase treatment the slope d/dPj, which at low pressures represents synovial hydraulic conductance, increased from a control of 0.90 ± 0.20 μl min−1 cmH2O−1 (mean ± s.e.m., n = 6) to 4.52 ± 0.70 μl min−1 cmH2O−1. The slope d/dPj increased to a similar level after testicular hyaluronidase, namely to 4.14 ± 1.06 μl min−1 cmH2O−1 (control, 0.54 ± 0.24 μl min−1 cmH2O−1). Streptomyces and leech hyaluronidases were as effective as testicular hyaluronidase (no statistically significant differences) despite differences in substrate specificity. It was shown using histochemical and immunohistochemical techniques that hyaluronan was removed from the synovium by leech, Streptomyces and testicular hyaluronidases. The binding of antibodies 2-B-6 and 3-B-3 showed that the core proteins of the chondroitin sulphate proteoglycans remained intact after treatment with hyaluronidases, and the binding of 5-D-4 showed that keratan sulphate was unaffected. An azocasein digestion assay confirmed that the hyaluronidase preparations had no significant proteolytic activity. The effect of the hyaluronidases was four times greater than predicted from the low concentration of interstitial hyaluronan and its resistivity. Factors that might amplify the effect of hyaluronan depletion include the matrix-organizing role of hyaluronan, and/or non-uniformity of hyaluronan distribution. It is concluded that interstitial hyaluronan makes a major contribution to synovial hydraulic resistance, but the mechanisms are as yet poorly understood. PMID:9596792

Interstitial Fe in MgO

NASA Astrophysics Data System (ADS)

Mølholt, T. E.; Mantovan, R.; Gunnlaugsson, H. P.; Svane, A.; Masenda, H.; Naidoo, D.; Bharuth-Ram, K.; Fanciulli, M.; Gislason, H. P.; Johnston, K.; Langouche, G.; Ólafsson, S.; Sielemann, R.; Weyer, G.

2014-01-01

Isolated 57Fe atoms were studied in MgO single-crystals by emission Mössbauer spectroscopy following implantation of 57Mn decaying to 57Fe. Four Mössbauer spectral components were found corresponding to different Fe lattice positions and/or charge states. Two components represent Fe atoms substituting Mg as Fe2+ and Fe3+, respectively; a third component is due to Fe in a strongly implantation-induced disturbed region. The fourth component, which is the focus of this paper, can be assigned to Fe at an interstitial site. Comparison of its measured isomer shift with ab initio calculations suggests that the interstitial Fe is located on, or close to, the face of the rock-salt MgO structure. To harmonize such an assignment with the measured near-zero quadrupole interaction a local motion process (cage motion) of the Fe has to be stipulated. The relation of such a local motion as a starting point for long range diffusion is discussed.

Estimating Plasma Glucose from Interstitial Glucose: The Issue of Calibration Algorithms in Commercial Continuous Glucose Monitoring Devices

PubMed Central

Rossetti, Paolo; Bondia, Jorge; Vehí, Josep; Fanelli, Carmine G.

2010-01-01

Evaluation of metabolic control of diabetic people has been classically performed measuring glucose concentrations in blood samples. Due to the potential improvement it offers in diabetes care, continuous glucose monitoring (CGM) in the subcutaneous tissue is gaining popularity among both patients and physicians. However, devices for CGM measure glucose concentration in compartments other than blood, usually the interstitial space. This means that CGM need calibration against blood glucose values, and the accuracy of the estimation of blood glucose will also depend on the calibration algorithm. The complexity of the relationship between glucose dynamics in blood and the interstitial space, contrasts with the simplistic approach of calibration algorithms currently implemented in commercial CGM devices, translating in suboptimal accuracy. The present review will analyze the issue of calibration algorithms for CGM, focusing exclusively on the commercially available glucose sensors. PMID:22163505

Deriving Sediment Interstitial Water Remediation Goals ...

EPA Pesticide Factsheets

This document contains a methodology for developing interstitial water remediation goals (IWRGs) for nonionic organic pollutants (toxicants) in sediments for the protection of benthic organisms. The document provides the basis for using the final chronic values (FCVs) from EPA’s aquatic water quality criteria (AWQC) for the protection of aquatic life to set the IWRGs for toxicants in sediments. Concentrations of the toxicants in the sediment interstitial water are measured using passive sampling. This document also discusses how to evaluate the consistency between passive sampling measurements and sediment toxicity test results. When these data are consistent, one can be reasonably assured that the causes of toxicity to benthic organisms in the sediment have been correctly identified and that the developed IWRGs for the toxicants will be protective of the benthic organisms at the site. The consistency evaluation is an important step in developing defensible IWRGs. To assist in developing defensible IWRGs.

Wearable physiological systems and technologies for metabolic monitoring.

PubMed

Gao, Wei; Brooks, George A; Klonoff, David C

2018-03-01

Wearable sensors allow continuous monitoring of metabolites for diabetes, sports medicine, exercise science, and physiology research. These sensors can continuously detect target analytes in skin interstitial fluid (ISF), tears, saliva, and sweat. In this review, we will summarize developments on wearable devices and their potential applications in research, clinical practice, and recreational and sporting activities. Sampling skin ISF can require insertion of a needle into the skin, whereas sweat, tears, and saliva can be sampled by devices worn outside the body. The most widely sampled metabolite from a wearable device is glucose in skin ISF for monitoring diabetes patients. Continuous ISF glucose monitoring allows estimation of the glucose concentration in blood without the pain, inconvenience, and blood waste of fingerstick capillary blood glucose testing. This tool is currently used by diabetes patients to provide information for dosing insulin and determining a diet and exercise plan. Similar technologies for measuring concentrations of other analytes in skin ISF could be used to monitor athletes, emergency responders, warfighters, and others in states of extreme physiological stress. Sweat is a potentially useful substrate for sampling analytes for metabolic monitoring during exercise. Lactate, sodium, potassium, and hydrogen ions can be measured in sweat. Tools for converting the concentrations of these analytes sampled from sweat, tears, and saliva into blood concentrations are being developed. As an understanding of the relationships between the concentrations of analytes in blood and easily sampled body fluid increases, then the benefits of new wearable devices for metabolic monitoring will also increase.

Deformation strain is the main physical driver for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation.

PubMed

Ramani-Mohan, Ram-Kumar; Schwedhelm, Ivo; Finne-Wistrand, Anna; Krug, Melanie; Schwarz, Thomas; Jakob, Franz; Walles, Heike; Hansmann, Jan

2018-03-01

Mesenchymal stem cells play a major role during bone remodelling and are thus of high interest for tissue engineering and regenerative medicine applications. Mechanical stimuli, that is, deformation strain and interstitial fluid-flow-induced shear stress, promote osteogenic lineage commitment. However, the predominant physical stimulus that drives early osteogenic cell maturation is not clearly identified. The evaluation of each stimulus is challenging, as deformation and fluid-flow-induced shear stress interdepend. In this study, we developed a bioreactor that was used to culture mesenchymal stem cells harbouring a strain-responsive AP-1 luciferase reporter construct, on porous scaffolds. In addition to the reporter, mineralization and vitality of the cells was investigated by alizarin red staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Quantification of the expression of genes associated to bone regeneration and bone remodelling was used to confirm alizarin red measurements. Controlled perfusion and deformation of the 3-dimensional scaffold facilitated the alteration of the expression of osteogenic markers, luciferase activity, and calcification. To isolate the specific impact of scaffold deformation, a computational model was developed to derive a perfusion flow profile that results in dynamic shear stress conditions present in periodically loaded scaffolds. In comparison to actually deformed scaffolds, a lower expression of all measured readout parameters indicated that deformation strain is the predominant stimulus for skeletal precursors to undergo osteogenesis in earlier stages of osteogenic cell maturation. Copyright © 2017 John Wiley & Sons, Ltd.

Mechanisms of sampling interstitial fluid from skin using a microneedle patch.

PubMed

Samant, Pradnya P; Prausnitz, Mark R

2018-05-01

Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of >1 µL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (µpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusion < capillary action < osmosis < pressure-driven convection, under the conditions studied. These findings were in agreement with independent theoretical modeling that considered transport within skin, across the interface between skin and µpores, and within µpores to the skin surface. This analysis indicated that the rate-limiting step for ISF sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration.

PubMed

Fry, Brendan C; Edwards, Aurélie; Layton, Anita T

2015-05-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2 (-)) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2 (-) concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2 (-), the effects of NO and O2 (-) on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. Copyright © 2015 the American Physiological Society.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

PubMed Central

Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles.

PubMed

Orel, V B; Zabolotny, M A; Orel, V E

2017-05-01

Tumour hypoxia leads to radio and chemotherapy resistance among cancer patients. The aim of this paper is to formulate a hypothesis on the heterogeneity of hypoxia in solid tumours. Tumour vasculature is known to be significantly variable. The great structural and functional abnormalities of tumour microcirculation cause spatial and temporal heterogeneity in its perfusion. Tumours have constantly been under the influence of pulsatile blood perfusion with variable pressure that initiates inhomogeneous erythrocyte deformation and following impact on oxygen disorder release from red blood cells into plasma within the blood vessel. Furthermore, stochastically released oxygen in tumour vessel, plasma and interstitial fluid may lead to heterogeneity of hypoxia. Under the influence of increased heterogeneity of hemodynamic force, the oxygen molecules dissolved in blood plasma are inclined to form nanobubbles (NBs) in tumour vessels. Considering the fact that tumour interstitial fluid pressure is increased compared to normal tissues, we assume that oxygen NBs may burst under the impact of shear stress. During the course of mechanochemical reaction, when a nanobubble (NB) bursts, both reactive oxygen species and ions form in various charged states. In consequence of a chain reaction, free radical oxygen molecules bind to proteins and lipids, thus reducing oxygen molecules in a chaotic manner within the tumour. The proposed hypothesis should be used as a methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on NB conglomerates with drugs in the tumour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fabrication and characterization of a pd nanowire-based glucose biofuel cell

NASA Astrophysics Data System (ADS)

Amoah, Kweku Obeng

The use of glucose as a source in biofuel cell technology has received a lot of attention in part due to the potential applications of such systems. In addition to the being a clean energy alternative, it provides a pathway for implantable microelectronic devices, such as pacemakers, to be powered by interstitial fluid and eliminate the need for batteries. Furthermore, using interstitial fluid as fuel sources will drastically reduce necessary invasive surgeries to replace batteries. Additionally, cost to such patients will be reduced while quality of life enhanced. The research presents a unique platform for harvesting energy from glucose. Using semiconductor cleanroom techniques, electrically conductive palladium nanowires are grown on anodized aluminum oxide templates using silicon and glass as supporting substrates. Photolithography is used to create two non-continuous gold windows and contact pads on the substrates. AAO templates are attached to the two gold windows and palladium nanowires are electrochemically grown on the AAO templates. Glucose oxidase and catalase are immobilized on the anode and laccase on the cathode. In the presence of glucose, electrons are released that result in the generation of voltage and current. The current-voltage behavior of the fuel cell, as well as electrochemical properties, is characterized using standard performance metrics. In 5 mM glucose solution with a neutral pH of 7.3, the open circuit voltage obtained was 335 mV and the short circuit current of 6 microA to yield a maximum power output of 1.38 microW.

Assessment of the Alteration of Granitic Rocks and its Influence on Alkalis Release

NASA Astrophysics Data System (ADS)

Ferraz, Ana Rita; Fernandes, Isabel; Soares, Dora; Santos Silva, António; Quinta-Ferreira, Mário

2017-12-01

Several concrete structures had shown signs of degradation some years after construction due to internal expansive reactions. Among these reactions there are the alkali-aggregate reactions (AAR) that occur between the aggregates and the concrete interstitial fluids which can be divided in two types: the alkali-silica reaction (ASR) and alkali-carbonate reaction (ACR). The more common is the ASR which occurs when certain types of reactive silica are present in the aggregates. In consequence, an expansive alkali-silica gel is formed leading to the concrete cracking and degradation. Granites are rocks composed essentially of quartz, micas and feldspars, the latter being the minerals which contain more alkalis in their structure and thus, able to release them in conditions of high alkalinity. Although these aggregates are of slow reaction, some structures where they were applied show evidence of deterioration due to ASR some years or decades after the construction. In the present work, the possible contribution of granitic aggregates to the interstitial fluids of concrete by alkalis release was studied by performing chemical attack with NaOH and KOH solutions. Due to the heterogeneity of the quarries in what concerns the degree of alteration and/or fracturing, rock samples with different alteration were analysed. The alteration degree was characterized both under optical microscope and image analysis and compared with the results obtained from the chemical tests. It was concluded that natural alteration reduces dramatically the releasable alkalis available in the rocks.

3D Numerical Prediction of Gas-Solid Flow Behavior in CFB Risers for Geldart A and B Particles

NASA Astrophysics Data System (ADS)

Özel, A.; Fede, P.; Simonin, O.

In this study, mono-disperse flows in squared risers conducted with A and B-type particles were simulated by Eulerian n-fluid 3D unsteady code. Two transport equations developed in the frame of kinetic theory of granular media supplemented by the interstitial fluid effect and the interaction with the turbulence (Balzer et al., 1996) are resolved to model the effect of velocity fluctuations and inter-particle collisions on the dispersed phase hydrodynamic. The studied flow geometries are three-dimensional vertical cold channels excluding cyclone, tampon and returning pipe of a typical circulating fluidized bed. For both type of particles, parametric studies were carried out to determine influences of boundary conditions, physical parameters and turbulence modeling. The grid dependency was analyzed with mesh refinement in horizontal and axial directions. For B-type particles, the results are in good qualitative agreement with the experiments and numerical predictions are slightly improved by the mesh refinement. On the contrary, the simulations with A-type particles show a less satisfactory agreement with available measurements and are highly sensitive to mesh refinement. Further studies are carried out to improve the A-type particles by modeling subgrid-scale effects in the frame of large-eddy simulation approach.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI.

PubMed

Iliff, Jeffrey J; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-03-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer's disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer's disease susceptibility and progression in the live human brain.

Brain-wide pathway for waste clearance captured by contrast-enhanced MRI

PubMed Central

Iliff, Jeffrey J.; Lee, Hedok; Yu, Mei; Feng, Tian; Logan, Jean; Nedergaard, Maiken; Benveniste, Helene

2013-01-01

The glymphatic system is a recently defined brain-wide paravascular pathway for cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange that facilitates efficient clearance of solutes and waste from the brain. CSF enters the brain along para-arterial channels to exchange with ISF, which is in turn cleared from the brain along para-venous pathways. Because soluble amyloid β clearance depends on glymphatic pathway function, we proposed that failure of this clearance system contributes to amyloid plaque deposition and Alzheimer’s disease progression. Here we provide proof of concept that glymphatic pathway function can be measured using a clinically relevant imaging technique. Dynamic contrast-enhanced MRI was used to visualize CSF-ISF exchange across the rat brain following intrathecal paramagnetic contrast agent administration. Key features of glymphatic pathway function were confirmed, including visualization of para-arterial CSF influx and molecular size-dependent CSF-ISF exchange. Whole-brain imaging allowed the identification of two key influx nodes at the pituitary and pineal gland recesses, while dynamic MRI permitted the definition of simple kinetic parameters to characterize glymphatic CSF-ISF exchange and solute clearance from the brain. We propose that this MRI approach may provide the basis for a wholly new strategy to evaluate Alzheimer’s disease susceptibility and progression in the live human brain. PMID:23434588

Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring.

PubMed

Sharma, Sanjiv; Huang, Zhenyi; Rogers, Michelle; Boutelle, Martyn; Cass, Anthony E G

2016-11-01

We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T 90 ) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3-6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these. Graphical Abstract Microneedle arrays for continuous glucose monitoring in dermal interstitial fluid.

Markers of cartilage and synovial metabolism in joint fluid and serum of patients with chondromalacia of the patella.

PubMed

Väätäinen, U; Lohmander, L S; Thonar, E; Hongisto, T; Agren, U; Rönkkö, S; Jaroma, H; Kosma, V M; Tammi, M; Kiviranta, I

1998-03-01

To further our understanding of the pathogenesis of chondromalacia of the patella (CM), we have studied the release into knee joint fluid and serum, obtained from patients with CM, of molecules associated with the metabolism of joint cartilage matrix and synovium. Interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), stromelysin-1 (MMP-3), interstitial collagenase (MMP-1), tissue inhibitor for metalloproteinases-1 (TIMP-1), phospholipase activity A2 (PLA2), hyaluronan (HA), aggrecan fragments (AGN) and antigenic keratan sulfate (KS) were quantified in knee joint lavage fluid from 96 patients with CM; KS and HA also was measured in serum. Chondromalacia was graded on a scale of I to IV according to Outerbridge (1961). The histopathology of the synovial membrane close to the patellofemoral joint was evaluated. Control samples were obtained from nine patients with knee pain presenting with arthroscopically normal knee joints. The concentrations of MMP-3, MMP-1 and TIMP-1 proteins in joint lavage fluid were increased in advanced (grade IV) CM, compared with controls. Levels of MMP-1 in lavage fluid correlated with the severity of CM (r = 0.38, P < 0.01) and MMP-1 and MMP-3 concentrations correlated with each other (r = 0.45, P < 0.001). TIMP-1 was elevated in grade IV CM compared with grades II and III CM (P < 0.02, P < 0.01). Interleukins (IL-1 alpha, IL-1 beta and IL-6) showed no significant change in CM. The lavage fluid level of PLA2 increased with the severity of CM (r = 0.40, P < 0.001). Serum KS was higher in CM IV than in controls (P = 0.05), while lavage fluid KS concentration was elevated in CM I (P = 0.04). There were no differences in the lavage fluid levels of AGN and HA between the different study groups. Synovium showed slight or moderate histological signs of inflammation in 9% of CM patients. The changes in the release and activity of these marker molecules from serum and synovial fluid may reflect changes in the metabolism of articular cartilage and synovium in CM, that are consistent with those observed in early-stage tibiofemoral cartilage changes in OA.

The effect of creep on human lumbar intervertebral disk impact mechanics.

PubMed

Jamison, David; Marcolongo, Michele S

2014-03-01

The intervertebral disk (IVD) is a highly hydrated tissue, with interstitial fluid making up 80% of the wet weight of the nucleus pulposus (NP), and 70% of the annulus fibrosus (AF). It has often been modeled as a biphasic material, consisting of both a solid and fluid phase. The inherent porosity and osmotic potential of the disk causes an efflux of fluid while under constant load, which leads to a continuous displacement phenomenon known as creep. IVD compressive stiffness increases and NP pressure decreases as a result of creep displacement. Though the effects of creep on disk mechanics have been studied extensively, it has been limited to nonimpact loading conditions. The goal of this study is to better understand the influence of creep and fluid loss on IVD impact mechanics. Twenty-four human lumbar disk samples were divided into six groups according to the length of time they underwent creep (tcreep = 0, 3, 6, 9, 12, 15 h) under a constant compressive load of 400 N. At the end of tcreep, each disk was subjected to a sequence of impact loads of varying durations (timp = 80, 160, 320, 400, 600, 800, 1000 ms). Energy dissipation (ΔE), stiffness in the toe (ktoe) and linear (klin) regions, and neutral zone (NZ) were measured. Analyzing correlations with tcreep, there was a positive correlation with ΔE and NZ, along with a negative correlation with ktoe. There was no strong correlation between tcreep and klin. The data suggest that the IVD mechanical response to impact loading conditions is altered by fluid content and may result in a disk that exhibits less clinical stability and transfers more load to the AF. This could have implications for risk of diskogenic pain as a function of time of day or tissue hydration.

An observational and thermodynamic investigation of carbonate partial melting

NASA Astrophysics Data System (ADS)

Floess, David; Baumgartner, Lukas P.; Vonlanthen, Pierre

2015-01-01

Melting experiments available in the literature show that carbonates and pelites melt at similar conditions in the crust. While partial melting of pelitic rocks is common and well-documented, reports of partial melting in carbonates are rare and ambiguous, mainly because of intensive recrystallization and the resulting lack of criteria for unequivocal identification of melting. Here we present microstructural, textural, and geochemical evidence for partial melting of calcareous dolomite marbles in the contact aureole of the Tertiary Adamello Batholith. Petrographic observations and X-ray micro-computed tomography (X-ray μCT) show that calcite crystallized either in cm- to dm-scale melt pockets, or as an interstitial phase forming an interconnected network between dolomite grains. Calcite-dolomite thermometry yields a temperature of at least 670 °C, which is well above the minimum melting temperature of ∼600 °C reported for the CaO-MgO-CO2-H2O system. Rare-earth element (REE) partition coefficients (KDcc/do) range between 9-35 for adjacent calcite-dolomite pairs. These KD values are 3-10 times higher than equilibrium values between dolomite and calcite reported in the literature. They suggest partitioning of incompatible elements into a melt phase. The δ18O and δ13C isotopic values of calcite and dolomite support this interpretation. Crystallographic orientations measured by electron backscattered diffraction (EBSD) show a clustering of c-axes for dolomite and interstitial calcite normal to the foliation plane, a typical feature for compressional deformation, whereas calcite crystallized in pockets shows a strong clustering of c-axes parallel to the pocket walls, suggesting that it crystallized after deformation had stopped. All this together suggests the formation of partial melts in these carbonates. A Schreinemaker analysis of the experimental data for a CO2-H2O fluid-saturated system indeed predicts formation of calcite-rich melt between 650-880 °C, in agreement with our observations of partial melting. The presence of partial melts in crustal carbonates has important physical and chemical implications, including a drastic drop in rock viscosity and significant change in the dynamics and distribution of fluids within both the contact aureole and the intrusive body.

Cold-water acclimation does not modify whole-body fluid regulation during subsequent cold-water immersion.

PubMed

Stocks, J M; Patterson, M J; Hyde, D E; Jenkins, A B; Mittleman, K D; Taylor, N A S

2004-06-01

We investigated the impact of cold-water acclimation on whole-body fluid regulation using tracer-dilution methods to differentiate between the intracellular and extracellular fluid compartments. Seven euhydrated males [age 24.7 (8.7) years, mass 74.4 (6.4) kg, height 176.8 (7.8) cm, sum of eight skinfolds 107.4 (20.4) mm; mean (SD)] participated in a 14-day cold-water acclimation protocol, with 60-min resting cold-water stress tests [CWST; 18.1 (0.1) degrees C] on days 1, 8 and 15, and 90-min resting cold-water immersions [18.4 (0.4) degrees C] on intervening days. Subjects were immersed to the 4th intercostal space. Intracellular and extracellular fluid compartments, and plasma protein, electrolyte and hormone concentrations were investigated. During the first CWST, the intracellular fluid (5.5%) and plasma volumes were reduced (6.1%), while the interstitial fluid volume was simultaneously expanded (5.4%). This pattern was replicated on days 8 and 15, but did not differ significantly among test days. Acclimation did not produce significant changes in the pre-immersion distribution of total body water, or changes in plasma osmolality, total protein, electrolyte, atrial natriuretic peptide or aldosterone concentrations. Furthermore, a 14-day cold-water acclimation regimen did not elicit significant changes in body-fluid distribution, urine production, or the concentrations of plasma protein, electrolytes or the fluid-regulatory hormones. While acclimation trends were not evident, we have confirmed that fluid from extravascular cells is displaced into the interstitium during acute cold-water immersion, both before and after cold acclimation.

Investigating cerebral oedema using poroelasticity.

PubMed

Vardakis, John C; Chou, Dean; Tully, Brett J; Hung, Chang C; Lee, Tsong H; Tsui, Po-Hsiang; Ventikos, Yiannis

2016-01-01

Cerebral oedema can be classified as the tangible swelling produced by expansion of the interstitial fluid volume. Hydrocephalus can be succinctly described as the abnormal accumulation of cerebrospinal fluid (CSF) within the brain which ultimately leads to oedema within specific sites of parenchymal tissue. Using hydrocephalus as a test bed, one is able to account for the necessary mechanisms involved in the interaction between oedema formation and cerebral fluid production, transport and drainage. The current state of knowledge about integrative cerebral dynamics and transport phenomena indicates that poroelastic theory may provide a suitable framework to better understand various diseases. In this work, Multiple-Network Poroelastic Theory (MPET) is used to develop a novel spatio-temporal model of fluid regulation and tissue displacement within the various scales of the cerebral environment. The model is applied through two formats, a one-dimensional finite difference - Computational Fluid Dynamics (CFD) coupling framework, as well as a two-dimensional Finite Element Method (FEM) formulation. These are used to investigate the role of endoscopic fourth ventriculostomy in alleviating oedema formation due to fourth ventricle outlet obstruction (1D coupled model) in addition to observing the capability of the FEM template in capturing important characteristics allied to oedema formation, like for instance in the periventricular region (2D model). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways

PubMed Central

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed

2016-01-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid. PMID:27306753

Paravascular channels, cisterns, and the subarachnoid space in the rat brain: A single compartment with preferential pathways.

PubMed

Bedussi, Beatrice; van der Wel, Nicole N; de Vos, Judith; van Veen, Henk; Siebes, Maria; VanBavel, Ed; Bakker, Erik Ntp

2017-04-01

Recent evidence suggests an extensive exchange of fluid and solutes between the subarachnoid space and the brain interstitium, involving preferential pathways along blood vessels. We studied the anatomical relations between brain vasculature, cerebrospinal fluid compartments, and paravascular spaces in male Wistar rats. A fluorescent tracer was infused into the cisterna magna, without affecting intracranial pressure. Tracer distribution was analyzed using a 3D imaging cryomicrotome, confocal microscopy, and correlative light and electron microscopy. We found a strong 3D colocalization of tracer with major arteries and veins in the subarachnoid space and large cisterns, attributed to relatively large subarachnoid space volumes around the vessels. Confocal imaging confirmed this colocalization and also revealed novel cisternal connections between the subarachnoid space and ventricles. Unlike the vessels in the subarachnoid space, penetrating arteries but not veins were surrounded by tracer. Correlative light and electron microscopy images indicated that this paravascular space was located outside of the endothelial layer in capillaries and just outside of the smooth muscle cells in arteries. In conclusion, the cerebrospinal fluid compartment, consisting of the subarachnoid space, cisterns, ventricles, and para-arteriolar spaces, forms a continuous and extensive network that surrounds and penetrates the rat brain, in which mixing may facilitate exchange between interstitial fluid and cerebrospinal fluid.

A new look at cerebrospinal fluid circulation

PubMed Central

2014-01-01

According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

XFEM modeling of hydraulic fracture in porous rocks with natural fractures

NASA Astrophysics Data System (ADS)

Wang, Tao; Liu, ZhanLi; Zeng, QingLei; Gao, Yue; Zhuang, Zhuo

2017-08-01

Hydraulic fracture (HF) in porous rocks is a complex multi-physics coupling process which involves fluid flow, diffusion and solid deformation. In this paper, the extended finite element method (XFEM) coupling with Biot theory is developed to study the HF in permeable rocks with natural fractures (NFs). In the recent XFEM based computational HF models, the fluid flow in fractures and interstitials of the porous media are mostly solved separately, which brings difficulties in dealing with complex fracture morphology. In our new model the fluid flow is solved in a unified framework by considering the fractures as a kind of special porous media and introducing Poiseuille-type flow inside them instead of Darcy-type flow. The most advantage is that it is very convenient to deal with fluid flow inside the complex fracture network, which is important in shale gas extraction. The weak formulation for the new coupled model is derived based on virtual work principle, which includes the XFEM formulation for multiple fractures and fractures intersection in porous media and finite element formulation for the unified fluid flow. Then the plane strain Kristianovic-Geertsma-de Klerk (KGD) model and the fluid flow inside the fracture network are simulated to validate the accuracy and applicability of this method. The numerical results show that large injection rate, low rock permeability and isotropic in-situ stresses tend to lead to a more uniform and productive fracture network.

Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).

PubMed

Mace, T F

1976-01-01

Adult Dioctophyma renale occupied the enlarged renal pelvis of the right kidney of naturally infected mink. Lesions in the kidney parenchyma consisted of connective tissue proliferation in the interstitial tissue, tubular atrophy and fibrosis, and periglomerular fibrosis. The luminal surface of the renal pelvis wall was formed of numerous papillae covered with transitional epithelium. The nematodes in the lumen were bathed in an albuminous fluid containing red blood cells, epithelial cells and D. renale eggs. The left (uninfected) kidney was 60% larger than the left kidney of normal mink.

Contact drying: a review of experimental and mechanistic modeling approaches.

PubMed

Sahni, Ekneet Kaur; Chaudhuri, Bodhisattwa

2012-09-15

Drying is one of the most complex unit operations with simultaneous heat and mass transfer. The contact drying process is also not well understood as several physical phenomena occur concurrently. This paper reviews current experimental and modeling approaches employed towards a better understanding of the contact drying operation. Additionally, an overview of some fundamental aspects relating to contact drying is provided. A brief discussion of some model extensions such as incorporation of noncontact forces, interstitial fluids and attrition rate is also presented. Copyright © 2012 Elsevier B.V. All rights reserved.

Evidence for independent motional processes on the two interstitial sublattices of a layer-structured metal hydride: Hydrogen spin-lattice relaxation and motional narrowing in zirconium monohalide hemihydrides, ZrXH0.5

NASA Astrophysics Data System (ADS)

Hwang, T. Y.; Schoenberger, R. J.; Torgeson, D. R.; Barnes, R. G.

1983-01-01

We report the results of a proton-magnetic-resonance investigation of hydrogen location and motion in the hemihydrides ZrXH0.5 of the metallic layer-structured monohalides ZrX of zirconium (X=Br,Cl). Wide-line and pulsed NMR methods were employed to measure the temperature dependence of the linewidth and second moment and of the spin-lattice relaxation time in the laboratory and rotating frames. The results indicate that hydrogen forms an ordered structure on the tetrahedral (T) interstitial sublattice within the Zr metal bilayers, with some (small) random occupancy of octahedral (O) sites. Two stages of motional narrowing observed in the wide-line measurements and double minima found in the relaxation times are consistent with the occurrence of essentially independent hydrogen motional processes on the T and O interstitial sublattices. Hydrogen site occupancy probabilities, jump frequencies, activation energies for hydrogen diffusion, and conduction-electron contributions to the proton spin-lattice relaxation rate are deduced from the measurements.

Radiation-enhanced self- and boron diffusion in germanium

NASA Astrophysics Data System (ADS)

Schneider, S.; Bracht, H.; Klug, J. N.; Hansen, J. Lundsgaard; Larsen, A. Nylandsted; Bougeard, D.; Haller, E. E.

2013-03-01

We report experiments on proton radiation-enhanced self- and boron (B) diffusion in germanium (Ge) for temperatures between 515 ∘C and 720 ∘C. Modeling of the experimental diffusion profiles measured by means of secondary ion mass spectrometry is achieved on the basis of the Frenkel pair reaction and the interstitialcy and dissociative diffusion mechanisms. The numerical simulations ascertain concentrations of Ge interstitials and B-interstitial pairs that deviate by several orders of magnitude from their thermal equilibrium values. The dominance of self-interstitial related defects under irradiation leads to an enhanced self- and B diffusion in Ge. Analysis of the experimental profiles yields data for the diffusion of self-interstitials (I) and the thermal equilibrium concentration of BI pairs in Ge. The temperature dependence of these quantities provides the migration enthalpy of I and formation enthalpy of BI that are compared with recent results of atomistic calculations. The behavior of self- and B diffusion in Ge under concurrent annealing and irradiation is strongly affected by the property of the Ge surface to hinder the annihilation of self-interstitials. The limited annihilation efficiency of the Ge surface can be caused by donor-type surface states favored under vacuum annealing, but the physical origin remains unsolved.

Zinc diffusion in gallium arsenide and the properties of gallium interstitials

NASA Astrophysics Data System (ADS)

Bracht, H.; Brotzmann, S.

2005-03-01

We have performed zinc diffusion experiments in gallium arsenide at temperatures between 620°C and 870°C with a dilute Ga-Zn source. The low Zn partial pressure established during annealing realizes Zn surface concentrations of ⩽2×1019cm-3 , which lead to the formation of characteristic S-shaped diffusion profiles. Accurate modeling of the Zn profiles, which were measured by means of secondary ion mass spectroscopy, shows that Zn diffusion under the particular doping conditions is mainly mediated by neutral and singly positively charged Ga interstitials via the kick-out mechanism. We determined the temperature dependence of the individual contributions of neutral and positively charged Ga interstitials to Ga diffusion for electronically intrinsic conditions. The data are lower than the total Ga self-diffusion coefficient and hence consistent with the general interpretation that Ga diffusion under intrinsic conditions is mainly mediated by Ga vacancies. Our results disprove the general accepted interpretation of Zn diffusion in GaAs via doubly and triply positively charged Ga interstitials and solves the inconsistency related to the electrical compensation of the acceptor dopant Zn by the multiply charged Ga interstitials.

Exploring the Virchow–Robin spaces function: A unified theory of brain diseases

PubMed Central

Cherian, Iype; Beltran, Margarita; Kasper, Ekkehard M.; Bhattarai, Binod; Munokami, Sunil; Grasso, Giovanni

2016-01-01

Background: Cerebrospinal fluid (CSF) transport across the central nervous system (CNS) is no longer believed to be on the conventional lines. The Virchow–Robin space (VRS) that facilitates CSF transport from the basal cisterns into the brain interstitial fluid (ISF) has gained interest in a whole new array of studies. Moreover, new line of evidence suggests that VRS may be involved in different pathological mechanisms of brain diseases. Methods: Here, we review emerging studies proving the feasible role of VRS in sleep, Alzheimer's disease, chronic traumatic encephalopathy, and traumatic brain injury (TBI). Results: In this study, we have outlined the possible role of VRS in different pathological conditions. Conclusion: The new insights into the physiology of the CSF circulation may have important clinical relevance for understanding the mechanisms underlying brain pathologies and their cure. PMID:27857861

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

A mixture theory model of fluid and solute transport in the microvasculature of normal and malignant tissues. I. Theory.

PubMed

Schuff, M M; Gore, J P; Nauman, E A

2013-05-01

In order to better understand the mechanisms governing transport of drugs, nanoparticle-based treatments, and therapeutic biomolecules, and the role of the various physiological parameters, a number of mathematical models have previously been proposed. The limitations of the existing transport models indicate the need for a comprehensive model that includes transport in the vessel lumen, the vessel wall, and the interstitial space and considers the effects of the solute concentration on fluid flow. In this study, a general model to describe the transient distribution of fluid and multiple solutes at the microvascular level was developed using mixture theory. The model captures the experimentally observed dependence of the hydraulic permeability coefficient of the capillary wall on the concentration of solutes present in the capillary wall and the surrounding tissue. Additionally, the model demonstrates that transport phenomena across the capillary wall and in the interstitium are related to the solute concentration as well as the hydrostatic pressure. The model is used in a companion paper to examine fluid and solute transport for the simplified case of an axisymmetric geometry with no solid deformation or interconversion of mass.

Temporal gradients in shear stimulate osteoblastic proliferation via ERK1/2 and retinoblastoma protein

NASA Technical Reports Server (NTRS)

Jiang, Guang-Liang; White, Charles R.; Stevens, Hazel Y.; Frangos, John A.

2002-01-01

Bone cells are subject to interstitial fluid flow (IFF) driven by venous pressure and mechanical loading. Rapid dynamic changes in mechanical loading cause transient gradients in IFF. The effects of pulsatile flow (temporal gradients in fluid shear) on rat UMR106 cells and rat primary osteoblastic cells were studied. Pulsatile flow induced a 95% increase in S-phase UMR106 cells compared with static controls. In contrast, ramped steady flow stimulated only a 3% increase. Similar patterns of S-phase induction were also observed in rat primary osteoblastic cells. Pulsatile flow significantly increased relative UMR106 cell number by 37 and 62% at 1.5 and 24 h, respectively. Pulsatile flow also significantly increased extracellular signal-regulated kinase (ERK1/2) phosphorylation by 418%, whereas ramped steady flow reduced ERK1/2 activation to 17% of control. Correspondingly, retinoblastoma protein was significantly phosphorylated by pulsatile fluid flow. Inhibition of mitogen-activated protein (MAP)/ERK kinase (MEK)1/2 by U0126 (a specific MEK1/2 inhibitor) reduced shear-induced ERK1/2 phosphorylation and cell proliferation. These findings suggest that temporal gradients in fluid shear stress are potent stimuli of bone cell proliferation.

Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System

PubMed Central

Badhan, Raj K. Singh; Chenel, Marylore; Penny, Jeffrey I.

2014-01-01

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. PMID:24647103

Hydrogen Passivation of Interstitial Zn Defects in Heteroepitaxial InP Cell Structures and Influence on Device Characteristics

NASA Technical Reports Server (NTRS)

Ringel, S. A.; Chatterjee, B.

2004-01-01

Hydrogen passivation of heteroepitaxial InP solar cells is of recent interest for deactivation of dislocations and other defects caused by the cell/substrate lattice mismatch that currently limit the photovoltaic performance of these devices. In this paper we present strong evidence that, in addition to direct hydrogen-dislocation interactions, hydrogen forms complexes with the high concentration of interstitial Zn defects present within the p(+) Zn-doped emitter of MOCVD-grown heteroepitaxial InP devices, resulting in a dramatic increase of the forward bias turn-on voltage by as much as 280 mV, from 680 mV to 960 mV. This shift is reproducible and thermally reversible and no such effect is observed for either n(+)p structures or homoepitaxial p(+)n structures grown under identical conditions. A combination of photoluminescence (PL), electrochemical C-V dopant profiling, SIMS and I-V measurements were performed on a set of samples having undergone a matrix of hydrogenation and post-hydrogenation annealing conditions to investigate the source of this voltage enhancement and confirm the expected role of interstitial Zn and hydrogen. A precise correlation between all measurements is demonstrated which indicates that Zn interstitials within the p(+) emitter and their interaction with hydrogen are indeed responsible for this device behavior.

Survey and evaluation of multilayer insulation heat transfer measurements

NASA Astrophysics Data System (ADS)

Doenecke, Jochen

About 40 papers treating multilayer insulations were studied and compared. Most of these papers present heat transfer measurements in addition to thermal analysis. Here the equations are given which are required for an evaluation of the measurements and in particular for comparisons. Equations are presented which are required to predict the influences of the packing density, temperatures, fraction of perforation area and interstitial pressure. The equation giving gas conductivity versus pressure is modified according to measurements. In space the interstitial pressure is usually below 0.01 Pa and the heat transfer can be expressed as the sum of a conductive and radiative term. The equation finally proposed for spacecraft permits to consider the influence of temperature, number of layers, blanket size and perforation area.

Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

NASA Technical Reports Server (NTRS)

Tohda, Koji; Gratzl, Miklos

2004-01-01

Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of patients with moderate to severe diabetes: a growing health problem in the US and World-wide.

Microdialysis assessment of shock wave lithotripsy-induced renal injury.

PubMed

Brown, S A; Munver, R; Delvecchio, F C; Kuo, R L; Zhong, P; Preminger, G M

2000-09-01

Shock wave lithotripsy (SWL) is the primary treatment modality for managing the majority of symptomatic renal calculi. However, the fundamental mechanisms for stone fragmentation and the resultant morphologic changes that occur are not fully understood. Furthermore, a thorough understanding of the complex biologic pathways involved in SWL-induced renal injury does not exist at present. To elucidate the biologic processes involved in tissue injury after SWL, an animal model was designed to mimic the pathogenesis of high-energy SWL in humans. Juvenile female swine were anesthetized, and a midline laparotomy incision was performed to expose the right kidney. Using an introducer apparatus, a microdialysis probe was placed into the renal parenchyma of the right kidney lower pole and a tunnel was generated to exit the distal ends of the inlet and outlet tubing outside the body. After a 72-hour postoperative recovery period, SWL was performed to the lower pole renal region of the kidney, as a microdialysis pump continuously infused dialysate through the inlet tubing. Microdialysis fluids were collected during SWL, and lipid peroxidation, as measured by conjugated diene concentrations, was monitored. All microdialysis probes remained patent for a total of 2000 shock waves. A significant elevation in conjugated diene levels was observed in the SWL versus untreated kidneys after 1000 shock waves were administered (P <0.02). This animal model is unique in that it represents the first system for the real-time collection of renal interstitial fluids during SWL. Analysis of this fluid may provide insight into the physiologic mechanisms responsible for shock wave-induced renal injury.

A tumor growth model with deformable ECM

NASA Astrophysics Data System (ADS)

Sciumè, G.; Santagiuliana, R.; Ferrari, M.; Decuzzi, P.; Schrefler, B. A.

2014-12-01

Existing tumor growth models based on fluid analogy for the cells do not generally include the extracellular matrix (ECM), or if present, take it as rigid. The three-fluid model originally proposed by the authors and comprising tumor cells (TC), host cells (HC), interstitial fluid (IF) and an ECM, considered up to now only a rigid ECM in the applications. This limitation is here relaxed and the deformability of the ECM is investigated in detail. The ECM is modeled as a porous solid matrix with Green-elastic and elasto-visco-plastic material behavior within a large strain approach. Jauman and Truesdell objective stress measures are adopted together with the deformation rate tensor. Numerical results are first compared with those of a reference experiment of a multicellular tumor spheroid (MTS) growing in vitro, then three different tumor cases are studied: growth of an MTS in a decellularized ECM, growth of a spheroid in the presence of host cells and growth of a melanoma. The influence of the stiffness of the ECM is evidenced and comparison with the case of a rigid ECM is made. The processes in a deformable ECM are more rapid than in a rigid ECM and the obtained growth pattern differs. The reasons for this are due to the changes in porosity induced by the tumor growth. These changes are inhibited in a rigid ECM. This enhanced computational model emphasizes the importance of properly characterizing the biomechanical behavior of the malignant mass in all its components to correctly predict its temporal and spatial pattern evolution.

Long-term temperature monitoring at the biological community site on the Nankai accretionary prism off Kii Peninsula

NASA Astrophysics Data System (ADS)

Goto, S.; Hamamoto, H.; Yamano, M.; Kinoshita, M.; Ashi, J.

2008-12-01

Nankai subduction zone off Kii Peninsula is one of the most intensively surveyed areas for studies on the seismogenic zone. Multichannel seismic reflection surveys carried out in this area revealed the existence of splay faults that branched from the subduction zone plate boundary [Park et al., 2002]. Along the splay faults, reversal of reflection polarity was observed, indicating elevated pore fluid pressure along the faults. Cold seepages with biological communities were discovered along a seafloor outcrop of one of the splay faults through submersible observations. Long-term temperature monitoring at a biological community site along the outcrop revealed high heat flow carried by upward fluid flow (>180 mW/m2) [Goto et al., 2003]. Toki et al. [2004] estimated upward fluid flow rates of 40-200 cm/yr from chloride distribution of interstitial water extracted from sediments in and around biological community sites along the outcrop. These observation results suggest upward fluid flow along the splay fault. In order to investigate hydrological nature of the splay fault, we conducted long-term temperature monitoring again in the same cold seepage site where Goto et al. [2003] carried out long-term temperature monitoring. In this presentation, we present results of the temperature monitoring and estimate heat flow carried by upward fluid flow from the temperature records. In this long-term temperature monitoring, we used stand-alone heat flow meter (SAHF), a probe-type sediment temperature recorder. Two SAHFs (SAHF-3 and SAHF-4) were used in this study. SAHF-4 was inserted into a bacterial mat, within several meters of which the previous long-term temperature monitoring was conducted. SAHF-3 was penetrated into ordinary sediment near the bacterial mat. The sub-bottom temperature records were obtained for 8 months. The subsurface temperatures oscillated reflecting bottom- water temperature variation (BTV). For sub-bottom temperatures measured with SAHF-3 (outside of the bacterial mat), we found that the effects of the BTV propagated into sediment by conduction only. By correcting the effect of the BTV, conductive heat flow estimated is higher than 100 mW/m2. Sub-bottom temperatures measured within bacterial mat (SAHF-4) except for the topmost sensor could be explained by a conduction model. The heat flow estimated based on the conduction model is similar to that measured with SAHF-3. The temperature of the topmost sensor is slightly higher than that expected from the conduction model. To explain the high temperature, upward fluid flow at a rate of 10-7 m/s order is needed. Heat flow carried by the upward fluid flow is higher than that estimated by Goto et al. [2003]. Heat flow value expected from the distribution of heat flow around this area is 70-80 mW/m2. The high heat flow values inside and outside the bacterial mat estimated in the present and previous studies may reflect upward fluid flow along the splay fault.

Radiation damage and defect behavior in proton irradiated lithium-counterdoped n+p silicon solar cells

NASA Technical Reports Server (NTRS)

Stupica, John; Goradia, Chandra; Swartz, Clifford K.; Weinberg, Irving

1987-01-01

Two lithium-counterdoped n+p silicon solar cells with different lithium concentrations were irradiated by 10-MeV protons. Cell performance was measured as a function of fluence, and it was found that the cell with the highest concentration of lithium had the highest radiation resistance. Deep level transient spectroscopy which showed two deep level defects that were lithium related. Relating the defect energy levels obtained from this study with those from earlier work using 1-MeV electron irradiation shows no correlation of the defect energy levels. There is one marked similarity: the absence of the boron-interstitial-oxygen-interstitial defect. This consistency strengthens the belief that lithium interacts with oxygen to prevent the formation of the boron interstitial-oxygen interstitial defect. The results indicate that, in general, addition of lithium in small amounts to the p-base of a boron doped silicon solar cell such that the base remains p-type, tends to increase the radiation resistance of the cell.

A Poroelastic Fluid/Structure-Interaction Model of Cerebrospinal Fluid Dynamics in the Cord With Syringomyelia and Adjacent Subarachnoid-Space Stenosis.

PubMed

Bertram, C D; Heil, M

2017-01-01

An existing axisymmetric fluid/structure-interaction (FSI) model of the spinal cord, pia mater, subarachnoid space, and dura mater in the presence of syringomyelia and subarachnoid-space stenosis was modified to include porous solids. This allowed investigation of a hypothesis for syrinx fluid ingress from cerebrospinal fluid (CSF). Gross model deformation was unchanged by the addition of porosity, but pressure oscillated more in the syrinx and the subarachnoid space below the stenosis. The poroelastic model still exhibited elevated mean pressure in the subarachnoid space below the stenosis and in the syrinx. With realistic cord permeability, there was slight oscillatory shunt flow bypassing the stenosis via the porous tissue over the syrinx. Weak steady streaming flow occurred in a circuit involving craniocaudal flow through the stenosis and back via the syrinx. Mean syrinx volume was scarcely altered when the adjacent stenosis bisected the syrinx, but increased slightly when the syrinx was predominantly located caudal to the stenosis. The fluid content of the tissues over the syrinx oscillated, absorbing most of the radial flow seeping from the subarachnoid space so that it did not reach the syrinx. To a lesser extent, this cyclic swelling in a boundary layer of cord tissue just below the pia occurred all along the cord, representing a mechanism for exchange of interstitial fluid (ISF) and cerebrospinal fluid which could explain recent tracer findings without invoking perivascular conduits. The model demonstrates that syrinx volume increase is possible when there is subarachnoid-space stenosis and the cord and pia are permeable.

Bladder irrigation and urothelium disruption: a reminder apropos of a case of fatal fluid absorption.

PubMed

Di Paolo, Marco; Bugelli, Valentina; Di Luca, Alessandro; Turillazzi, Emanuela

2014-11-20

Irrigation or washouts of the bladder are usually performed in various clinical settings. In the 1980s Elliot and colleagues argued that urothelial damage could occur after washouts and irrigations of the bladder. The exact mechanism underlying urothelial damage has not yet been discovered. To our knowledge, this is the first report of fatal fluid overload and pulmonary edema, due to urothelium disruption occurring during bladder irrigation, approached performing complete histological and immunohistochemical investigation on bladder specimens. The exposed case deserves attention since it demonstrates that, although very rarely, irrigation or washouts of the bladder may have unexpected serious clinical consequences. An 85 year-old Caucasian man, unable to eat independently and whose fluid intake was controlled, underwent continuous bladder irrigation with a 3-way catheter due to a severe episode of macrohematuria. During the third day of hospitalization, while still undergoing bladder irrigation, he suddenly experienced extreme shortness of breath, breathing difficulties, and cough with frothy sputum. His attending nurse immediately noted that there was no return of the fluid (5 liters) introduced through bladder irrigation. He was treated urgently with hemodialysis. At the beginning of the dialysis treatment, the patient had gained 7.4 kg since the previous measurement (24 hours prior) without any clear explanation. Although a significant weight loss (from 81 to 76 kg) due to the dialysis procedure, the patient died shortly after the final treatment. The autopsy revealed that the brain and the lungs were heavily edematous. Microscopic examination of bladder specimens revealed interstitial and mucosal swelling, and loss of the superficial cell layer. Intermediate and basal urothelial cells were preserved. Altogether the above mentioned findings were suggestive of a diffuse disruption of the urothelium. In conclusion the death of the man was attributed to an acute severe pulmonary edema due to massive fluid absorption. Our case demonstrates that urothelium disruption may occur during irrigation and washouts of the bladder, also in the absence of other well-known predisposing conditions. Inappropriate use of bladder irrigation should be avoided and a close attention is required of the fluid balance is mandatory when irrigating the bladder.

Pressure monitoring during lipofilling procedures.

PubMed

Klein, S M; Prantl, L; Geis, S; Eisenmann-Klein, M; Dolderer, J; Felthaus, O; Loibl, M; Heine, N

2014-01-01

Grafting of autologous lipoaspirate for various clinical applications has become a common procedure in clinical practice. With an estimated mortality rate of 10-15 percent, fat embolism is among the most severe complications to be expected after lipofilling therapies. The aim of this study was to determine the level of interstitial pressure after the injection of defined volumes of lipoaspirate into the subcutaneous tissue of female breasts. It was hypothesized, that interstitial pressure levels exceed the physiologic capillary pressure during lipofilling procedures and hence increase the potential risk for fat embolism. Further it was investigated if external tissue expansion has the potential to significantly reduce interstitial tissue pressure. Interstitial pressure was monitored in 36 female patients, that underwent autologous fat injections into the breast. Measurements were conducted with a sensor needle connected to a pressure transducer (LogiCal Pressure Monitoring Kit, Smiths medical int. Ltd., UK). Patients were divided into 4 subcohorts differing in their pre-treatment regimen or local tissue conditions. Pre-treatment consisted of tissue expansion, achieved with the Brava™ (Brava LLC Miami, Fla., USA) vacuum-chamber. The increase in interstitial pressure after injection volumes of 100 ml (p = 0.006), 200 ml (p = 0.000) and between 100 ml and 200 ml (p = 0.004) respectively, were significant in non-mastectomized patients without pre-treatment. Patients pre-treated with Brava™ did not show such statistically significant differences in interstitial pressures before and after the injection of 100 ml and 200 ml of lipoaspirate (p = 0.178). The difference in interstitial pressure in mastectomized patients between 0 ml and 100 ml (p = 0.003), as well as 0 ml and 200 ml (p = 0.028) was significant. The difference in pressures between pre-treated patients and patients without pre-treatment did not differ significantly in the mastectomized patient cohort. During lipofilling procedures interstitial pressures are reached that exceed pressure limits defined as hazardous for fat embolism. To date it is unknown what pressure levels need to be considered critical for complications in soft tissue interventions. Further the results indicate higher interstitial pressures for patients that had undergone mastectomy, whereas pre-treatment with external tissue expansion seemed to diminish pressure values.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

PubMed Central

Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

2015-01-01

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150

Correlation of gene expression with bladder capacity in interstitial cystitis/bladder pain syndrome.

PubMed

Colaco, Marc; Koslov, David S; Keys, Tristan; Evans, Robert J; Badlani, Gopal H; Andersson, Karl-Erik; Walker, Stephen J

2014-10-01

Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Masimo Rad-57 Pulse CO-Oximeter for noninvasive carboxyhemoglobin measurement.

PubMed

Suner, Selim; McMurdy, John

2009-03-01

Noninvasive methods of body fluid chemical measurement have been expanding. New technologies are enabling the quantification of different compounds in the blood and interstitial tissues. One example of this is the pulse oximeter, which has facilitated the measurement of oxyhemoglobin rapidly and reliably without the requirement of blood-draws. The Masimo Rad-57 Pulse CO-Oximeter expanded the capabilities of pulse-oximetry to include measurements of carboxyhemoglobin and methemoglobin. This innovation has revolutionized the paradigm for detection of patients with CO poisoning. Previously, clinicians relied on historical information and patient signs and symptoms pointing to the possibility of CO exposure or toxicity. Only then would a blood test be ordered to measure carboxyhemoglobin levels. Since the presentation of CO poisoning is nonspecific and overlaps with many other conditions, and since the presence of environmental CO is often unknown, the detection of this condition was only possible in cases where the presence of CO was obvious or where the symptoms were severe. We now know, from studies conducted using the Rad-57, the only US FDA-approved device for noninvasive measurement of SpCO, that there are a significant number of patients who experience CO exposure but are nonsymptomatic. The Rad-57 provides a clinical justification for screening in the healthcare setting to identify patients with significant CO exposure who would otherwise be undetected.

Osimertinib-induced interstitial lung disease after treatment with anti-PD1 antibody.

PubMed

Mamesaya, Nobuaki; Kenmotsu, Hirotsugu; Katsumata, Mineo; Nakajima, Takashi; Endo, Masahiro; Takahashi, Toshiaki

2017-02-01

We report a case of a 38-year-old woman who was diagnosed with stage IV lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790 M mutation on exon 20. The patient was treated with osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) following treatment with nivolumab, an anti-Programmed Cell Death 1 (anti-PD1) antibody. After initiating osimertinib treatment, the patient began to complain of low-grade fever and shortness of breath without hypoxemia, and her chest radiograph and a CT scan revealed a remarkable antitumor response, although faint infiltrations were observed in the bilateral lung field. Bronchoalveolar lavage fluid mainly contained lymphocytes (CD4+/CD8+ ratio of 0.3), and a transbronchial lung biopsy specimen showed lymphocytic alveolitis with partial organization in several alveolar spaces. Therefore we diagnosed the patient with osimertinib-induced interstitial lung disease (ILD) after treatment with anti-PD1 antibody. We considered anti-PD1 therapies may be the risk factor of EGFR-TKI-induced ILD.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

NASA Astrophysics Data System (ADS)

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-07-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50-100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering.

Bio-Fluid Dynamics in a Centimeter-Scale Diagnostics Incubator with Integrated Perfusion

NASA Astrophysics Data System (ADS)

Vukasinovic, J.; Cullen, D. K.; Glezer, A.; Laplaca, M. C.

2006-11-01

Growing demands for long-term incubation of biologically faithful, three-dimensional neuronal and other cultures during extended physiological studies require efficient perfusion platforms with functional vasculatures that mimic the in vivo condition in a thermally regulated environment. While thermostatically controlled incubation baths with capillary action perfusion are available, their use is confined to specific experimental conditions. The interstitial nutrient and gas delivery remains diffusion limited over the long term and cultures decay metabolically. To overcome these problems, we describe simple fabrication and experimental characterization of a compact, diagnostics incubator that allows in situ monitoring of culture activity with a superior control of critical biological functions using convectively enhanced heat and mass transport. To overcome intercellular diffusion barriers culture is exposed to a direct flow of media issuing from an array of micro-nozzles that are directed normal to the substrate upholding the culture, and further improved by 3-D convection induced by jet interactions and biased, peripheral perfusate extraction through an array of microchannels as demonstrated by microPIV measurements.

Effects of water immersion to the neck on pulmonary circulation and tissue volume in man

NASA Technical Reports Server (NTRS)

Begin, R.; Epstein, M.; Sackner, M. A.; Levinson, R.; Dougherty, R.; Duncan, D.

1976-01-01

A rapid noninvasive breathing method is used to obtain serial measurements of the pulmonary capillary blood flow, diffusing capacity per unit of alveolar volume, combined pulmonary tissue plus capillary volume, functional residual capacity, and oxygen consumption in five normal subjects undergoing 6 h of sitting, 4 h of sitting while immersed to the neck in thermoneutral water, and 4 h of lying in thermoneutral water to the neck. The rebreathing method employed a test gas mixture containing 0.5% C2H2, 0.3% C(18)O, 10% He, 21% O2, and balance N2. It is shown that immersion to the neck in the seated posture results in significant increases in sodium excretion cardiac output, and diffusing capacity per unit of alveolar volume. The pulmonary tissue plus capillary volume did not change, demonstrating that the central vascular engorgement induced by water immersion is not accompanied by significant extravasation of fluid into the pulmonary interstitial space.

Bronchial-arterial interdependence in isolated dog lung.

PubMed

Lai-Fook, S J; Kallok, M J

1982-04-01

The bronchus and artery, embedded in the lung parenchyma, were modeled as adjoining cylindrical tubes in an elastic continuum. Solutions using finite-element analysis of nonuniform stress and strain occurring from an initial uniform state were computed for a reduction in arterial pressure. Maximal nonuniform principal and shear stresses in the parenchyma, equal to 2.5 times the mean periarterial stresses, occurred in the region adjacent to the bronchial-arterial joint. Bronchial cross section became oval and elongated along the line passing through the centers of the tubes, whereas arterial cross section elongated at right angles to this line. These predicted changes in shape of bronchus and artery were verified by radiographic measurements in isolated lobes, held at constant transpulmonary pressures of 4 and 25 cmH2O while arterial pressure was varied. Results suggest that peribronchovascular interstitial fluid pressure may be nonuniform and that the bronchial-arterial joint may be the preferential site for emphysematous perivascular lesions, which may occur on lung hyperinflation.

Quantum cascade lasers (QCLs) in biomedical spectroscopy.

PubMed

Schwaighofer, Andreas; Brandstetter, Markus; Lendl, Bernhard

2017-10-02

Quantum cascade lasers (QCL) are the first room temperature semiconductor laser source for the mid-IR spectral region, triggering substantial development for the advancement of mid-IR spectroscopy. Mid-IR spectroscopy in general provides rapid, label-free and objective analysis, particularly important in the field of biomedical analysis. Due to their unique properties, QCLs offer new possibilities for development of analytical methods to enable quantification of clinically relevant concentration levels and to support medical diagnostics. Compared to FTIR spectroscopy, novel and elaborated measurement techniques can be implemented that allow miniaturized and portable instrumentation. This review illustrates the characteristics of QCLs with a particular focus on their benefits for biomedical analysis. Recent applications of QCL-based spectroscopy for analysis of a variety of clinically relevant samples including breath, urine, blood, interstitial fluid, and biopsy samples are summarized. Further potential for technical advancements is discussed in combination with future prospects for employment of QCL-based devices in routine and point-of-care diagnostics.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

PubMed Central

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-01-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50–100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering. PMID:27380889

Functional and magnetic resonance imaging correlates of corpus callosum in normal pressure hydrocephalus before and after shunting

PubMed Central

Mataró, Maria; Matarín, Mar; Poca, Maria Antonia; Pueyo, Roser; Sahuquillo, Juan; Barrios, Maite; Junqué, Carme

2007-01-01

Background Normal pressure hydrocephalus (NPH) is associated with corpus callosum abnormalities. Objectives To study the clinical and neuropsychological effect of callosal thinning in 18 patients with idiopathic NPH and to investigate the postsurgical callosal changes in 14 patients. Methods Global corpus callosum size and seven callosal subdivisions were measured. Neuropsychological assessment included an extensive battery assessing memory, psychomotor speed, visuospatial and frontal lobe functioning. Results After surgery, patients showed improvements in memory, visuospatial and frontal lobe functions, and psychomotor speed. Two frontal corpus callosum areas, the genu and the rostral body, were the regions most related to the clinical and neuropsychological dysfunction. After surgery, total corpus callosum and four of the seven subdivisions presented a significant increase in size, which was related to poorer neuropsychological and clinical outcome. Conclusion The postsurgical corpus callosum increase might be the result of decompression, re‐expansion and increase of interstitial fluid, although it may also be caused by differences in shape due to cerebral reorganisation. PMID:17056634

Nanorelief of the natural cleavage surface of triglycine sulphate crystals with substitutional and interstitial impurities

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

Belugina, N. V.; Gainutdinov, R. V.; Tolstikhina, A. L., E-mail: alla@ns.crys.ras.ru

2011-11-15

Ferroelectric triglycine sulphate crystals (TGS) with substitutional (LADTGS+ADP, DTGS) and interstitial (Cr) impurities have been studied by atomic-force microscopy, X-ray diffraction, and X-ray fluorescence. The nanorelief parameters of the mirror cleavage TGS(010) surface have been measured with a high accuracy. A correlation between the crystal defect density in the bulk and the cleavage surface nanorelief is revealed at the submicrometer level.

Multiaxial constitutive behavior of an interstitial-free steel: Measurements through X-ray and digital image correlation

PubMed Central

Jeong, Y.; Iadicola, M.A.; Gnäupel-Herold, T.; Creuziger, A.

2017-01-01

Constitutive behaviors of an interstitial-free steel sample were measured using an augmented Marciniak experiment. In these tests, multiaxial strain field data of the flat specimens were measured by the digital image correlation technique. In addition, the flow stress was measured using an X-ray diffractometer. The flat specimens in three different geometries were tested in order to achieve 1) balanced biaxial strain, and plane strain tests with zero strain in either 2) rolling direction or 3) transverse direction. The multiaxial stress and strain data were processed to obtain plastic work contours with reference to a uniaxial tension test along the rolling direction. The experimental results show that the mechanical behavior of the subjected specimen deviates significantly from isotropic behavior predicted by the von Mises yield criterion. The initial yield loci measured by a Marciniak tester is in good agreement with what is predicted by Hill's yield criterion. However, as deformation increases beyond the vonMises strain of 0.05, the shape of the work contour significantly deviates from that of Hill's yield locus. A prediction made by a viscoplastic self-consistent model is in better agreement with the experimental observation than the Hill yield locus with the isotropic work-hardening rule. However, none of the studied models matched the initial or evolving anisotropic behaviors of the interstitial-free steel measured by the augmented Marciniak experiment. PMID:28690400

Multiaxial constitutive behavior of an interstitial-free steel: Measurements through X-ray and digital image correlation.

PubMed

Jeong, Y; Iadicola, M A; Gnäupel-Herold, T; Creuziger, A

2016-06-15

Constitutive behaviors of an interstitial-free steel sample were measured using an augmented Marciniak experiment. In these tests, multiaxial strain field data of the flat specimens were measured by the digital image correlation technique. In addition, the flow stress was measured using an X-ray diffractometer. The flat specimens in three different geometries were tested in order to achieve 1) balanced biaxial strain, and plane strain tests with zero strain in either 2) rolling direction or 3) transverse direction. The multiaxial stress and strain data were processed to obtain plastic work contours with reference to a uniaxial tension test along the rolling direction. The experimental results show that the mechanical behavior of the subjected specimen deviates significantly from isotropic behavior predicted by the von Mises yield criterion. The initial yield loci measured by a Marciniak tester is in good agreement with what is predicted by Hill's yield criterion. However, as deformation increases beyond the vonMises strain of 0.05, the shape of the work contour significantly deviates from that of Hill's yield locus. A prediction made by a viscoplastic self-consistent model is in better agreement with the experimental observation than the Hill yield locus with the isotropic work-hardening rule. However, none of the studied models matched the initial or evolving anisotropic behaviors of the interstitial-free steel measured by the augmented Marciniak experiment.