Net Water Movement Research Articles

IMG-05. INITIAL RADIOGRAPHIC ASSESSMENT OF DWI AND ADC VALUES IN CHILDREN AND YOUNG ADULTS TREATED WITH DAY101 (TAK-580) FOR RECURRENT LOW-GRADE GLIOMAS (LGG) HARBORING MAPK ALTERATIONS

BACKGROUNDApparent diffusion coefficient (ADC) is a quantitative measure reflecting observed net movement of water calculated from a diffusion-weighted image (DWI), correlating with tumor cellularity. The higher cellularity of high-grade gliomas results in diffusion restriction and reduced ADC values, whereas the lower cellularity of low-grade gliomas (LGGs) gives higher ADC values. Here we examine changes in ADC values in patients with LGGs treated with the type 2 RAF inhibitor DAY101 (formerly TAK580).METHODSHistorical, baseline, and on-treatment brain MRIs for 9 patients enrolled on a phase 1 study of DAY101 in children and young adults with radiographically recurrent or progressive LGG harboring MAPK pathway alterations were obtained, de-identified and independently evaluated for ADC changes. Time points included baseline, first follow-up, and best response. Data processing of ADC estimates was performed using pmod molecular image software package. ADC changes were displayed as a histogram with mean values. Results were based upon a single read paradigm.RESULTSThere was a clear shift to lower ADC values for the solid component of tumors, reflecting changes in cellularity and tissue organization, while necrosis correlated with a shift toward higher ADC values. DWI reveals reduced ADCs in responding tumors, with the percent change in ADC from baseline correlating with deeper RANO responses.CONCLUSIONDWI analysis reveals reductions in ADC values that correlates with treatment response and a shift toward more normal cellularity in tumors treated with DAY101. Changes in ADC may represent a novel imaging biomarker, reflecting biological response to DAY101 treatment.

BIOM-37. INITIAL RADIOGRAPHIC ASSESSMENT OF ADC VALUES IN PEDIATRIC PATIENTS TREATED WITH DAY101 FOR RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMAS (LGGs) HARBORING MEK/ERK PATHWAY ALTERATIONS

Abstract BACKGROUND Calculated from a diffusion-weight image (DWI), the apparent diffusion coefficient (ADC) is a quantitative measure that reflects observed net movement of water and correlates to tumor cellularity. We examine the changes in ADC values in patients with LGG treated with dimeric, pan-RAF inhibitor DAY101 (formerly TAK-580/MLN2480). METHODS Focusing on ADC change with treatment, we reviewed historical, baseline, and on-treatment brain MRIs for 9 patients enrolled on our institutional, IRB-approved phase 1 trial of DAY101 in children and young adults with radiographically recurrent or progressive LGG harboring MEK/ERK pathway alterations. De-identified DICOM MRI files were independently reviewed. Time points selected included baseline, first follow-up and best response. The pmod molecular image software package was utilized for data processing of ADC estimates. ADC changes were displayed as a histogram with mean values. Results were based upon a single read paradigm. RESULTS A shift to lower ADC values for solid components of these tumors was observed, reflecting cellularity and organization; while necrosis correlated with a shift toward higher ADC values. DWI results show reduced ADCs in responding patients, with greater percent change in ADC from baseline associated with deeper responses among treated patients. DWI for treated patients with resultant stable disease showed no significant change in ADC values from baseline while a shift toward higher ADC values was evident in treated, progressing tumors. CONCLUSION Preliminary DWI analysis reveals that a reduction in ADC values may correlate with treatment response and a shift toward more normal cellularity in tumors treated with DAY101. This method will be applied to a larger cohort of patients in an ongoing phase 1 trial (NCT03429803) and a planned phase 2 trial.

Non-Equilibrium Mass Exchange in AOT Reverse Micelles.

Reverse micelles (RMs) composed of water and sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in isooctane have a remarkably narrow size distribution around a mean value determined by the water loading ratio of the system. It has been proposed that RMs establish this equilibrium size distribution either by the diffusion of individual components through the isooctane phase or by cycles of fusion and fission. To examine these mechanisms, a 24 μs all-atom molecular dynamics simulation of a system containing one small RM and one large RM was performed. Results show that the net movement of water from the small RM to the large RM occurred in a direction that made the small RM smaller and the large RM larger-according to water loading ratios that would have been appropriate for their size. Changes in AOT number that would bring the water loading ratio of each RM closer to that of the overall system only occurred via cycles of RM fusion and fission. These behaviors are most likely driven by the electrostatics of sodium AOT and the dielectric effects of water.

That's Swell! The Role of Aquaporin in an Inflammatory Response

Death due to lung inflammation has increased 31 percent over the last 35 years. A protein that influences this mortality rate is aquaporin‐4. This tetramer protein is a water channel that is water permeable. This integral protein, made up of six transmembrane helices and two pore helices, creates an hourglass shape. The structure of aquaporin is vital to its function due to pore helices preventing large molecules from passing through the membrane, only facilitating the movement of water molecules or small solutes. These two pore helices allow one molecule to pass at a time, making the net water movement facilitation easier. All types of aquaporins have NPA (asparagine‐proline‐alanine) motifs which are located in the central channel and are responsible for water permeation and intracellular processing. In aquaporin‐4, there are two NPA motifs at residues 97–99 and 213–215. Scientists discovered that aquaporin's response to bacterial stimuli can alter its pore size. Trauma, toxins or injury to tissue can cause a cell to become hypotonic. Aquaporin‐4 is specifically related to lung injury and inflammation because it is highly expressed in humans. The HUHS MAPS Team (Modeling A Protein Story) has designed a model of the wild form of AQP4 with 3D printing technology to investigate structure‐function relationships. The extensive research on aquaporins in relation to lung inflammation can contribute to the scientific and medical world and eventually target new pharmacological therapies.Support or Funding InformationThe MSOE Center for BioMolecular Modeling would like to acknowledge and thank the National Institutes of Health Clinical and Translational Science Award (NIH_CTSA UL1RR031973) and the Milwaukee School of Engineering for their support in funding the 2018_2019 SMART Team program.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Expression of NKCC1 and Aquaporins 4, 7 and 9 in Mouse Choroid Plexus and Ependymal Cells

Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) through poorly understood mechanisms involving Aquaporins (AQPs) and various solute transport proteins like the Na+/K+ pump and the Na+‐K+‐2Cl− cotransporter 1 (NKCC1). Net water movement across CPECs occurs from the basolateral membrane through the apical membrane. However, with the exception of AQP1 in the apical membrane, the molecular pathways for transepithelial water fluxes are either unknown, or their expression is controversial (Damkier et al. 2013, Physiol Rev 93, 1847). Because of their relatively high transcript expression (Cha et al, 2014, FASEB Journal 28 .1 Suppl 1182.3) the present work focuses on the cellular and subcellular localization of AQPs 4, 7 and 9 proteins in mouse CPECs and ependymal cells (EPCs), using immunolabeling with validated antibodies and confocal immuno‐fluorescence. Evidence for AQP4 expression in CPECs is controversial. The present results demonstrate that: 1) AQP 4 is expressed neither in CPECs nor in ependymal cells, but in radial glial endfeet surrounding the basal aspect of EPCs, where it is co‐expressed with NKCC1; the latter was also expressed in the apical membrane of both CPECs and EPCs; 2) AQP 7 expression was found to be restricted to the apical membrane of CPECs and EPCs. 3) AQP9 was expressed neither in CPECs nor in EPCs. The pathways for water influx across the basolateral membrane of CPECs remain to be elucidated. The pattern of expression of NKCC1 and AQP4 suggests a role of these proteins in K+ uptake from the CSF, both in CPECs and EPCs, thus regulating CSF and interstitial brain fluid [K+]. The expression of AQP7 in the apical membrane of CPECs suggests that this protein could work together with AQP1 in CSF secretion.Support or Funding Information(Supported by Wright State University Foundation FOAP 551462)

Interactive visual analytics of hydrodynamic flux for the coastal zone

Researchers wish to study the potential impact of sea level rise from climate change, and visual analytic tools can allow scientists to visually examine and explore different possible scenarios from simulation runs. In particular, hydrodynamic flux is calculated to understand the net movement of water; but typically this calculation is tedious and is not easily achieved with traditional visualization and analytic tools. We present a visual analytic method that incorporates a transect profiler and flux calculator. The analytic software is incorporated into our visual analytics tool Vinca, and generates multiple transects, which can be visualized and analysed in several alternative visualizations; users can choose specific transects to compare against real-world data; users can explore how flux changes within a domain. In addition, we report how ocean scientists have used our tool to display multiple-view views of their data and analyse hydrodynamic flux for the coastal zone.

Molecular pathways for water fluxes in mouse choroid plexus epithelial cells (1182.3)

Regulation and maintenance of cerebrospinal fluid (CSF) composition is crucial for brain function. Choroid plexus epithelial cells (CPECs) secrete most of the CSF and regulate its ion and water composition. However, the mechanisms of secretion and absorption of water across choroid plexus epithelium (CPE) are poorly understood. Secretion of CSF entails net water movement across CPECs from the basolateral membrane (blood‐facing) through the apical membrane (CSF‐facing). Water fluxes across cell membranes occur through aquaporin channels and cotransporters like the Na+‐K+‐2Cl‐ cotransporter 1 (NKCC1). Both NKCC1 and aquaporin‐1 (AQP1) are expressed in the CPECs apical membrane but are undetectable in the basolateral membrane. The inward water flux across the basolateral membrane of CPECs may be explained by the expression of other members of the gene families of AQPs and/or the cation‐coupled chloride cotransporters (slc12a). Using RT‐PCR, we detected transcripts for several AQPs in whole choroid plexus tissue. Transcripts for AQPs 1, 4, 7, but not 9, have so far been found. Immunolabeling studies in process will reveal the location of these proteins in the various components of the choroid plexus. Explaining the mechanisms of CSF production and absorption is key for understanding pathologies like hydrocephalous and increased intracranial pressure that cause brain ischemia and/or edema.Grant Funding Source: Supported by 226119 Seed Grant Proteomics Program 2012 Boonshoft School of Medicine

Simple model of megalopal transport in narrow river-dominated estuaries

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 452:179-191 (2012) - DOI: https://doi.org/10.3354/meps09605 Simple model of megalopal transport in narrow river-dominated estuaries Stephen A. Borgianini1,*, Richard Styles2, Renae J. Brodie3 1Department of Mathematics and Sciences, University of South Carolina Beaufort, Bluffton, South Carolina 29909, USA 2U.S. Army Corps of Engineers, Coastal and Hydraulics Laboratory, Engineer Research and Development Center, Vicksburg, Mississippi 39180, USA 3Department of Biological Sciences, Mount Holyoke College, South Hadley, Massachusetts 01075, USA *Email: borgians@uscb.edu ABSTRACT: In river-dominated estuaries such as Winyah Bay at the base of the Pee Dee River in South Carolina, USA, the net movement of water and pelagic larvae is toward the ocean. Larvae of many decapods are hypothesized to recruit back into estuaries using a complex behavior termed flood-tide transport (FTT). A pattern of late-stage larval behaviors in concert with daily tidal rhythms yields net larval transport upstream into the estuary. Tidal currents in narrow river channels exhibit little distortion of flow, resulting in near linear flows. This means that there is a linear decay in tidal current amplitude over the last few kilometers of the upper estuary that can be easily modeled with a simple 1-dimensional (1D) model. With our 1D model, we demonstrate that ebb and flood currents can be modeled accurately near the limit of maximum upstream tidal influence within narrow river-dominated estuaries. Our model predicts the damping of flood tidal current in the face of river discharge. This dampening restricts the upriver migration potential of larvae that use FTT to return to adult habitats, or colonize new habitat. When our model is coupled with FTT behavior, we can predict the ability of red-jointed fiddler crab Uca minax (LeConte 1855) larvae to recruit back to the freshwater reaches of the Pee Dee River estuary for any combination of river discharges or tidal amplitudes. The flow model we developed can be used to assess the potential impacts of changing river flow and sea level on larval recruitment to upstream areas of coastal rivers. KEY WORDS: Larval transport · Decapod larvae · Tidal currents · River discharge · Tidal freshwater · Modeling · Uca minax · Global warming Full text in pdf format PreviousNextCite this article as: Borgianini SA, Styles R, Brodie RJ (2012) Simple model of megalopal transport in narrow river-dominated estuaries. Mar Ecol Prog Ser 452:179-191. https://doi.org/10.3354/meps09605 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 452. Online publication date: April 25, 2012 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2012 Inter-Research.

Signals

Signals

Active Trans-Plasma Membrane Water Cycling in Yeast Is Revealed by NMR

Plasma membrane water transport is a crucial cellular phenomenon. Net water movement in response to an osmotic gradient changes cell volume. Steady-state exchange of water molecules, with no net flux or volume change, occurs by passive diffusion through the phospholipid bilayer and passage through membrane proteins. The hypothesis is tested that plasma membrane water exchange also correlates with ATP-driven membrane transport activity in yeast (Saccharomyces cerevisiae). Longitudinal 1H2O NMR relaxation time constant (T1) values were measured in yeast suspensions containing extracellular relaxation reagent. Two-site-exchange analysis quantified the reversible exchange kinetics as the mean intracellular water lifetime (τi), where τi−1 is the pseudo-first-order rate constant for water efflux. To modulate cellular ATP, yeast suspensions were bubbled with 95%O2/5%CO2 (O2) or 95%N2/5%CO2 (N2). ATP was high during O2, and τi−1 was 3.1 s−1 at 25°C. After changing to N2, ATP decreased and τi−1 was 1.8 s−1. The principal active yeast ion transport protein is the plasma membrane H+-ATPase. Studies using the H+-ATPase inhibitor ebselen or a yeast genetic strain with reduced H+-ATPase found reduced τi−1, notwithstanding high ATP. Steady-state water exchange correlates with H+-ATPase activity. At volume steady state, water is cycling across the plasma membrane in response to metabolic transport activity.

Chitosan enhances transcellular permeability in human and rat intestine epithelium

The intestinal epithelium regulates the transit of molecules from and into the organism. Several agents act as absorption enhancers inducing changes in both transcellular and paracellular routes. Chitosan is a non-toxic biocompatible polysaccharide widely used as dietary supplement and mucosal delivery. Chitosan triggers both the activation of intestinal epithelial cells and the release of regulatory factors relevant for its immunomodulatory activity. Yet, the interaction of chitosan with intestinal epithelial cells is poorly characterized. We studied the uptake of this polysaccharide, and we evaluated its effects in both the net water and ion movements across human and rat colon samples and the epithelial permeability. Herein, we demonstrate that chitosan increases the transcellular permeability to ions, water and protein markers in human and rat intestinal mucosa and decreases the water permeability across the paracellular pathway. These findings are relevant to understand the activity of the polysaccharide in the mucosal environment.

Field estimation of specific yield in a central Iowa crop field

AbstractThe specific yield (Sy) is the gain or loss of water associated with a corresponding amount of water table rise or fall. Rain may be intercepted by the canopy, refill the soil pore system, taken up by plant roots or drained. Transpired soil water may be replenished from a shallow water table, so water table loss is indirectly tied to evapotranspiration (ET). The purpose of this study was to use continuous data for the different components of the water cycle to back‐calculate Sy for both wetting and drying conditions. Two time periods were considered for a toeslope site in an Iowa corn (Zea mays L.) field: growing season from 22 June to 10 July 2007, and post‐growing season 13–30 October 2007. The field was instrumented with eddy covariance instrumentation for ET estimates, tipping bucket raingage for precipitation, automated well‐depth recorder for water table depth and water content reflectometers (CS616s) for soil water content. During drying in the growing season, mean Sy was 0·19, but drying Sy could not be determined post‐growing season because of no net upward water movement at this time. During wetting, estimates of Sy were improved when soil water increase was subtracted from total rainfall; then the mean wetting Sy was 0·052 versus 0·31–0·46 without this correction. Large differences between seasonal and post‐growing season data reflected the seasonal strong upward gradient created by soil dried from water uptake. Post‐growing season data was dominated by drainage, but seasonal root water uptake intercepted drainage water. Published in 2010 by John Wiley & Sons, Ltd.

A Simple Membrane Osmometer System & Experiments That Quantitatively Measure Osmotic Pressure

[ILLUSTRATION OMITTED] Students at all grade levels, including college, have difficulty understanding some of the fundamental concepts of diffusion and osmosis, and many of them carry misconceptions about these processes throughout their lives. Kose (2007) and Tekkaya (2003), building on the work of Odom and Kelly (2001), found that concept mapping was an effective tool in overcoming some of the misconceptions about both diffusion and osmosis. Similarly, Sanger et al. (2001) found that using computer animations of diffusion and osmosis helped students develop a better understanding of these processes. Other researchers reported that students who had laboratory experiences with osmosis and diffusion had a much greater understanding of osmotic principles compared to a group that only received the information through lecture (Marek et al., 1994). All of these approaches are consistent with recommendations of the National Science Education Standards (NRC, 1996) that strongly recommend the use of hands-on inquiry experiences to help increase students' understanding of scientific concepts. Much of the difficulty in understanding osmotic principles appears to lie in understanding and remembering terminology (Odom & Barrow, 2007). For example, the terms hypotonic, hypertonic, and isotonic refer to the relative concentrations of solutions separated by a semipermeable membrane. Many students are unable to state that water will move into a cell if it is placed in a hypotonic solution and out of a cell that is placed in a hypertonic solution. In the case of an isotonic solution, students can state that there is net movement of water across the cell membrane, but when they are asked to explain what this means, it becomes apparent that they do not understand that water molecules are moving through the membrane in both directions; they think that water molecules stop moving across membranes (Odom, 1995). Our experiences with prospective science teachers, as well as many in-service teachers, indicate that many of them struggle with explaining the mechanisms of water movement that accompany osmosis. Teachers, as well as most textbooks, tell students that water will diffuse into a cell if it is placed in a hypotonic solution. This statement does not intuitively fit the definition for diffusion of water because the terms refer to relative solute concentration. Consequently, teachers explain osmosis in terms that are based on the concentration differences of water. While this explanation is accurate and will correctly indicate the initial direction of water movement, it provides no information about the mechanisms driving osmosis. It is also misleading because water concentration per se does not play much of a role in osmosis; indeed, it is the solute concentration that contributes most significantly to the osmotic process (Salisbury & Ross, 1992; or most any other currently available plant physiology textbook). Perhaps an even more perplexing concept with which students and even teachers struggle is that of osmotic pressure. Osmotic pressure is classically defined as the hydrostatic pressure that balances the osmotic flow of water across a semipermeable membrane caused by solute concentration gradients. For students, this process appears to contradict what they have been told about diffusion and concentration gradients. To introduce the concept of osmotic pressure, a teacher will often show students a traditional osmometer that he/she has assembled, or more likely, a diagram of an osmometer from the textbook. The teacher explains that water diffuses across the membrane from the hypotonic side of the system into the osmometer, raising the water level. As the water level rises, the water column exerts a downward hydrostatic pressure resulting from the force of gravity. He/she continues to explain that water will rise in the osmometer until the hydrostatic pressure prevents the net flow of water across the membrane. …

Evaluation of the net water transport through electrolytes in Proton Exchange Membrane Fuel Cell

Electro-osmotic drag and back diffusion are the primary water transport mechanisms in PEMFC (Proton Exchange Membrane Fuel Cell) electrolytes. These two phenomena occur competitively in the membrane, and ultimately determine the net water movement. The chemical compositions of reactants and product (i.e., H 2, O 2, and H 2O) in a porous catalyst layer vary with respect to the electro-chemical reactions and water transport through the membrane. The tendency of the chemical compositions was estimated by analyzing the net water transport coefficient ( α), defined as the ratio of the reaction rate to the water transport rate. New criteria were suggested for predicting species mole fractions from the flow direction, and these were validated by CFD analysis. The hydrogen mole fraction had different tendencies to rise or fall based on the flow direction at α = 0.5, while the oxygen mole fraction extreme was located at α = −0.75. Finally, α was shown to influence the membrane conductivity and activation losses, which are the main factors that contribute to fuel cell performance.

Simple multichannel system for the measurement of the net water flux across biological tissues

This paper describes the development of a simple system for measurement of net water movement through biological membrane barriers. The system is based on the detection of a water meniscus inside a polyethylene tube, which reflects the water movement inside one hemichamber of a modified Ussing chamber containing a membrane barrier. The detection device consists of a commercial computer-controlled flat bed scanner and specifically developed software. This system allows one to perform a relatively high number of individual experiments per physical unit. It is a flexible and affordable device, which allows comparatively more information per unit to be obtained than previously described methods.

Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury

It is well established that posttraumatic secondary ischemia contributes to poor outcome. Ion dysfunction leading to cytotoxic edema is a primary force in the formation of ischemic brain edema and is a principal component of traumatic brain swelling. Because cell swelling is the result of net ion and water movement, it is crucial to have a thorough understanding of these transient phenomena. The purpose of this study was to characterize the effects of secondary ischemia following traumatic brain injury (TBI) on the ability to restore ion homeostasis. Twenty-four Sprague-Dawley rats were divided into four groups of six animals each. The rats underwent transient forebrain ischemia via bilateral carotid artery occlusion combined with hypotension: 15 minutes of forebrain ischemia (Group 1); 60 minutes of forebrain ischemia (Group 2); impact acceleration/TBI (Group 3); and impact acceleration/TBI followed by 15 minutes of ischemia (Group 4). Ischemia resulted in a rapid accumulation of [K+]e:41.94 +/- 13.65 and 66.33 +/- 6.63 mM, respectively, in Groups 1 and 2, with a concomitant decrease of [Na+]e:64 +/- 18 mM and 72 +/- 11 mM in Groups 1 and 2. Traumatic brain injury resulted in a less severe although identical trend in ion dysfunction ([K+]e 30.42 +/- 11.67 mM and [Na+]e 63 +/- 33 mM). Secondary ischemia resulted in prolonged and sustained ion dysfunction with a concomitant elevation of intracranial pressure (ICP). Analysis of these results indicates that ischemia and TBI are sublethal in isolation; however, when TBI is associated with secondary ischemia, ion dysfunction is sustained and is associated with elevated ICP.

New method to measure water permeability in emptied-out Xenopus oocytes controlling conditions on both sides of the membrane

Membrane water permeability is habitually calculated from volume changes in Xenopus laevis oocytes during external osmotic challenges. Nevertheless, this approach is limited by the uncertainty on the oocyte internal composition. To circumvent this limitation a new experimental set up is introduced where the cell membrane of an emptied-out oocyte was mounted as a diaphragm between two chambers. In its final configuration the oocyte membrane was part of a closed compartment and net water movements induced swelling or shrinking of it. Volume changes were followed by video-microscopy and digitally recorded. In this manner, water movements could be continuously monitored while controlling chemical composition and hydrostatic pressure on both sides of the membrane. Using this novel experimental approach an increasing hydrostatic pressure gradient was applied to both mature (stage VI) and immature (stage IV) oocytes. The relative maximal volume change tolerated before disruption was similar in both cases (1.26 ± 0.07 and 1.27 ± 0.03 respectively) and similar to those previously reported under maximal osmotic stress. Nevertheless the osmotic permeability coefficient ( P OSM) in mature oocytes ((1.72 ± 0.58) × 10 − 3 cm s − 1 ; n = 6) was significantly lower than in immature oocytes ((5.18 ± 0.59) × 10 − 3 cm s − 1 , n = 5; p < 0.005).

Spiral artery associated restricted growth (SPAARG): a computer model of pathophysiology resulting from low intervillous pressure having fetal programming implications

Failure of adequate trophoblastic conversion of maternal spiral arteries is associated with intrauterine growth restriction (IUGR). In addition to poor oxygen delivery, raised spiral artery resistance reduces placental intervillous pressure. An iterative type computer model was formed by linking an existing model of the fetus and a new nine cotyledon placental model. Simulation of compression cuffing of the spiral arteries to progressively restrict uteroplacental flow was performed, while observing various fetal and placental variables. Water moved to the fetus in the cotyledonary core villi, and to the mother in the outer villous layers. While the fetus could match villous capillary pressure to changes in intervillous pressure, net transplacental water movement was minimal, but when spiral artery resistance was increased sufficiently to cause mean intervillous pressure to fall below that which the fetus could match, a net flow to the mother appeared. That continued until the resulting fetal blood hemoconcentration produced a sufficient increase in colloid osmotic pressure to restrict further loss. All cells within the fetal-placental unit are then required to operate in an abnormal ionic environment, which may significantly affect systems such as the renin–angiotensin set-point, with implications for post-natal homeostasis such as control of adult blood pressure. Furthermore, in vivo, cells of the feto-placental unit respond to the increased intravascular osmotic pressure by production of intracellular osmolytes in order to match intracellular and vascular/interstitial osmotic pressures. This may explain the observed effects on postnatal water balance in growth restricted infants and could also provide a possible mechanism for the association of the systemic maternal complications associated with impaired placentation and reduced intervillus flow.

Effects of growth hormone on fluid homeostasis. Clinical and experimental aspects.

Regulation of body fluid homeostasis appears simple at first sight since daily sodium and water intake equals daily sodium and water output. The mechanisms enabling the body to excrete exactly the ingested and metabolically produced amounts of water and sodium are, however, complex and not completely understood. The factors regulating body fluid homeostasis may grossly be divided into humoral and physical factors. The former comprises among others the renin–angiotensin–aldosterone system (RAAS), arginine vasopressin (AVP), atrial natriuretic factor (ANF), and prostaglandins. The physical factors relate primarily to renal function and factors regulating osmotic pressure. Approximately 60% of body weight is water, which may be subdivided into intracellular volume (ICV) (40%) in which potassium and phosphate are the predominant cation and anion, respectively, and extracellular volume (ECV) (20%) dominated by sodium and chloride. ECV may further be subdivided into interstitial volume(15%) and plasma volume (PV) (5%) [1]. In principle ECV constitutes the internal environment, which is responsible for the transport of ions, nutrients and hormones vital to the cells. This term was introduced by the French physiologist, Claude Bernard, in 1885. The osmotic concentrations of ECV and ICV are equal under steady-state conditions, but any change result in an osmotic gradient and an immediate flux of water along this gradient until equilibrium is restored [2]. Hence a considerable passage of water occurs across the cell membrane, exemplified by the fact that the water content of an erythrocyte is exchanged 100 times per second without any netmovement of water [3]. Water passes mainly the cell membrane through protein channels, which in turn are influenced by osmotic differences generated by facilitated diffusion and active transport across the cell membrane. A normal subject ingests 2100ml water daily and synthesizes additionally 200ml by oxidation. Daily fluid output in a normal subject includes 700ml from the skin and lungs, 200ml from faeces, and sweat and a urinary output of 1400ml [4]. Between 5 and 10% of total body water is exchanged daily in healthy adults [1]. Total body water (TBW) is traditionally estimated by isotopic dilution. ECV and PV may also be estimated using this principle, whereas ICV assessment is calculated indirectly by combining measurements of TBW and ECV. The role of GH in this complex system is not fully established, but several reports suggest that it is important in body fluid regulation. More than 70 years ago anterior pituitary extracts were shown to induce fluid retention in rats [5] and two decades later GH-induced sodium and fluid retention was also demonstrated in man [6–8]. The sodiumand water-retaining effects of GH have subsequently been confirmed in several studies in normal man, in acromegalic patients and in GH-deficient patients [9–15]. Despite methodological heterogeneity most authors seem to agree that body fluid volume is decreased in GH-deficient adults and that GH treatment normalizes body fluid volume in these patients. There is also agreement that GH causes volume expansion, when administered in pharmacological doses to normal subjects and when secreted in excess in active acromegaly. Regarding the underlying mechanisms attention has focused on direct cellular action of GH [14] and a possible GH-induced stimulation of the renin–angiotensin– aldosterone system (RAAS) [8]. More recently other hormonal systems such as ANF [15], the prostaglandins [16], IGF-I [17], and nitric oxide [18] have been suggested to be involved. At present the sodium and fluidretaining effect of GH seems indisputable, whereas the underlying mechanisms appear to be diverse. www.elsevier.com/locate/ghir Growth Hormone & IGF Research 13 (2003) 55–74

Gum arabic (GA) modifies paracellular water and electrolyte transport in the small intestine.

Previous experiments have shown that a soluble fiber, gum arabic (GA), enhances water, electrolyte, and glucose absorption in animal models of diarrhea. The mechanisms implicated in this effect have not been fully elucidated. This study examined the possibility that paracellular transport is modulated by luminal GA, resulting in an enhanced rate of absorption in the small intestine. This hypothesis was tested by 3-hr jejunal perfusions on anesthetized rats with solutions containing 140 mM NaCl, 5 mM KCl, and 2 microCi/liter (74 kBq) 3H2O, with either 2.5 g/liter GA [+GA] or in its absence [CTL], and one of the following agents, capable of altering paracellular transport: chenodeoxycholic acid at 0.5 mM (CDC), 2,4,6-triaminopyrimidine (TAP) at 20 mM, and protamine at 100 mg/liter (PTM). Sodium, potassium, net water, and unidirectional water movement were measured. The addition of GA increased sodium absorption in perfusions with CDC, TAP, or PTM only. Similar effects by GA on net water absorption rates were obtained in tissues permeabilized with CDC and PTM; however, GA added to TAP did not normalize the reduction caused by TAP. Although PTM did not alter net water absorption, addition of GA to perfusates with PTM enhanced absorption values above those of CTL. GA reversed the strong negative effects of CDC on potassium absorption but was ineffective in this regard with TAP and PTM. The data obtained with those reagents that affect paracellular transport and the histological evidence support the view that GA promotes net absorption by this route in the small intestine of normal rats.