SEARCH · PubMed Health

Results for “EXTRACELLULAR SPACE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources

PubMed1988

Pulmonary vascular efflux of norepinephrine in Dahl rats susceptible or resistant to salt-induced hypertension.

The purpose of these studies was to determine whether the accumulation of norepinephrine by the pulmonary circulation is altered in the Dahl model of genetic hypertension. Pulmonary norepinephrine accumulation was evaluated by performing a compartmental analysis of the efflux of L-[3H]norepinephrine from perfused lungs after inhibition of the norepinephrine-metabolizing enzymes. The lungs were isolated from Dahl salt-hypertension-susceptible (S) and salt-hypertension-resistant (R) rats that had been on a high sodium diet for 3 weeks. In both S and R rats, norepinephrine was accumulated into a single compartment with an efflux half-time of approximately 23 min, in addition to its distribution in the extracellular space. The size of the extracellular space was significantly increased in the S rats, but there was no difference in the size of the compartment of L-[3H]norepinephrine efflux between S (6.4 +/- 1.2 ml/g) and R (3.7 +/- 0.7 ml/g) rats. These data indicate that impaired accumulation and efflux of norepinephrine by the lungs does not contribute to the pathogenesis of hypertension in Dahl S rats.

Animals↗

PubMed1995

Intracellular binding of the anti-inflammatory drug niflumic acid in the liver.

Intracellular binding of niflumic acid in the perfused rat liver was analyzed according to the model of Scatchard. The data for the binding isotherm were obtained from previously published indicator dilution experiments. The intracellular bound niflumic acid was calculated as the difference between total concentration and the concentration of the free form. The intracellular concentration of the free form was inferred from the concentration of the free form in the extracellular space under the assumption of equilibrative distribution. A Scatchard model with two classes of binding sites fits very well to the experimental curve. The high affinity class has a dissociation constant of 26.10 +/- 0.69 microM and a maximal binding capacity of 2.21 +/- 0.03 micromol (ml intracellular space)(-1); the low affinity class has a dissociation constant of 721.90 +/- 229.0 microM and a maximal binding capacity of 5.96 +/- 0.67 micromol (ml intracellular space)(-1). Probably, under in vivo conditions, the binding capacity in the cellular space exceeds that of the extracellular space. This phenomenon explains, partly at least, the high intracellular concentrations of niflumic acid found under in vivo conditions.

Animals↗

PubMed1997

Structural peculiarities of vascular dendritic cell tubulovesicular system in human atherosclerotic aorta.

The principal function of vascular dendritic cells has been suggested to be antigen processing/presentation but how this might occur is not clear. To find out whether the organisation of vascular dendritic cells might allow them to internalise antigens, we used electron microscopy to examine their fine cytoarchitectonics. Tubular and vesicular structures were observed to form continuous nets through which extracellular molecules might gain access to lysosomes. This suggests that vascular dendritic cells might be able to degrade antigens using the same mechanisms as occur in macrophages. We also speculate that antigen processing might be different between type I vascular dendritic cells which possess a hypertrophied tubulovesicular system and type II vascular dendritic cells where the tubulovesicular system is less prominent. The present work indicates that the tubulovesicular system is functionally associated with the extracellular space. This connection with the extracellular space through the system of cisterns and vesicles can allow the transport of different substances entering the cistern nets.

Aorta↗

PubMed1992

Cellular architecture in age-related human nuclear cataracts.

Age-related or senile human nuclear cataracts were examined using electron microscopy of thin sections prepared from thick vibrating-knife microtome sections of nuclei extracted by extracapsular surgery. The use of extended aldehyde-tannic acid fixation of 80-120-microns thick vibrating-knife microtome sections overcame the difficult problem of preserving the hardened nuclear core of aged lenses. Comparisons were made between a typical nuclear cataract, containing a central opacity and a transparent rim, and a more advanced, or mature, completely opaque nuclear cataract. The typical nuclear cataract contained no obvious cell disruption, cellular debris, or objects that readily could explain the central opacity. The fiber cells had intact uniformly stained cytoplasms with well-defined plasma membrane borders and gap junctions. The transparent rim and the nuclear core appeared similar, except that fiber cells in the nucleus were more condensed with more elaborate intercellular interdigitations. The mature cataract showed various types of cell disruption in the perimeter but not in the core of the nucleus. These disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. Because these potential scattering centers were not found in the nuclear core, they probably were not the sole cause of the observed opacity. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. Similar features, although less pronounced, were present in the typical nuclear cataract. It was concluded that massive cell disruption is not essential to the formation of a central nuclear opacity. Subtle structural changes, especially small fluctuations in protein density between adjacent cells and alterations of the membranes and the extracellular space, probably contribute significantly to the central opacities in human nuclear cataracts.

Aged↗

PubMed1981

The spaces between membrane bilayers within PNS myelin as characterized by X-ray diffraction.

X-ray diffraction data from a wide range of animals characterize the two spaces in the peripheral nervous system (PNS) and the central nervous system (CNS) myelins. The 'extracellular space' is nearly constant from species to species while the 'cytoplasmic space' is more variable. A profile of swollen rat sciatic myelin shows material projecting from the bilayer into the extracellular space. Interdigitating Po molecules therefore are proposed to separate neighboring myelin bilayers across the extracellular space in PNS.

Animals↗

PubMed1994

Comparison of diffusion-weighted MRI with changes in cell volume in a rat model of brain injury.

The precise mechanisms that underlie acute changes in tissue water diffusion following cerebral ischemia or related insults such as glutamate exposure remain unexplained, but it has been suggested that these may be caused by cell swelling due to water uptake. This study was undertaken to compare the changes observed in diffusion-weighted MR images with changes in the cellular volume measured by electrical impedance in a model of N-methyl-D-aspartate-induced brain injury in perinatal rats. The results show that the temporal course of the intensity changes in the diffusion-weighted images parallelled the progressive shrinkage of the extracellular space measured from the electrical impedance. After administration of the N-methyl-D-aspartate antagonist MK-801 the signal enhancement in the images was reversed, which paralleled the normalization of the extracellular space observed by the impedance measurements. It was estimated that the extracellular space decreased from 24 to 12% while the apparent diffusion coefficient of water decreased from 0.89 x 10(-9) in normal tissue to 0.42 x 10(-9) m2/s in tissue exposed to N-methyl-D-aspartate. These data indicate that changes in tissue water diffusion are related to changes in cell volume.

Animals↗

PubMed2003

Insertion of MP20 into lens fibre cell plasma membranes correlates with the formation of an extracellular diffusion barrier.

It is known that during lens differentiation a number of fibre cell specific membrane proteins change their expression profiles. In this study we have investigated how the profiles of the two most abundant fibre cell membrane proteins AQP0 (formerly known as Major Intrinsic Protein, MIP) and MP20 change as a function of fibre cell differentiation. While AQP0 was always found associated with fibre cell membranes, MP20 was initially found in the cytoplasm of peripheral fibre cells before becoming inserted into the membranes of deeper fibre cells. To determine at what stage in fibre cell differentiation MP20 becomes inserted into the membrane, sections were double-labelled with an antibody against MP20, and propidium iodide, a marker of cell nuclei. This showed that membrane insertion of MP20 occurs in a discrete transition zone that coincided with the degradation of cell nuclei. To test the significance of the membrane insertion of MP20 to overall lens function, whole lenses were incubated for varying times in a solution containing either Texas Red-dextran or Lucifer yellow as markers of extracellular space. Lenses were fixed and then processed for immunocytochemistry. Analysis of these sections showed that both tracer dyes were excluded from the extracellular space in an area that coincided with insertion of MP20 into the plasma membrane. Our results suggest that the insertion of MP20 into fibre cell membranes coincides with the creation of a barrier that restricts the diffusion of molecules into the lens core via the extracellular space.

Animals↗

PubMed1992

Extracellular intermediates of glucose metabolism: fluxes of endogenous lactate and alanine through extracellular pools in embryonic sympathetic ganglia.

The flux rates of lactate and alanine in and out of the cells of an intact tissue, which cannot be measured directly because some of the released materials are reabsorbed, were determined by computer analysis of uptakes and outputs by the whole tissue in the presence of various concentrations of these substances. The outputs of labeled lactate and alanine from [U-14C]glucose and the uptakes of [U-14C]lactate and [U-14C]alanine were measured on intact sympathetic ganglia excised from 15-day-old chicken embryos. The volume and time constant of the extracellular space were measured using labeled lactate, alanine, and sucrose. Models, which mathematically described the cellular uptakes and outputs as functions of the extracellular concentrations, were used to predict the exchanges that would be observed on the whole tissue, and their parameters were adjusted for best fit to the actual observations. The fitted models were then used to calculate the fluxes in and out of the cells and the concentrations in the extracellular space. The following results were obtained: (1) Cellular uptakes of lactate and alanine were both well described by familiar Michaelis-Menten kinetics. (2) The cellular output of [14C]-lactate from [14C]glucose declined with increase in the extracellular lactate concentration, whereas the cellular output of [14C]alanine from [14C]glucose rose with the extracellular alanine concentration. (3) Half-saturation values for cellular uptake, determined from the fitted equations, were 0.45 mM for lactate and 1.17 mM for alanine, both several-fold lower than less relevant estimates for the whole tissue made directly from the uptake observations. (4) As much as 45% of the carbon in the glucose consumed was released into the extracellular space as lactate and alanine, but much of this was reabsorbed. Implications for brain metabolism are discussed.

Alanine↗

PubMed1988

Clinical and experimental studies on permeability of tracers in normal spinal cord and syringomyelia.

Delayed CT Myelography (CTM) demonstrated intramedullary cavities in 18 patients, most of which appeared on the 6-hour scan. The attenuation values of the normal spinal cord increased progressively with time, and recorded a peak at 6 hours. The CT numbers of the gray matter of metrizamide were significantly high, as compared with those of iotrol. In the tracer study reported, lanthanum penetrated through the marginal glia to the normal and pathologic spinal cord. Reaction products of horseradish peroxidase (HRP) were mainly in the extracellular space of the normal spinal cord. The pathologic spinal cord, however, allowed the passage of HRP into the parenchyma through the extracellular space of the marginal glia. Consequently, the extracellular space of the spinal cord surface constitutes a pathway for cerebrospinal fluid solutes. Either metrizamide or iotrol thus diffuses into the spinal cord from the subarachnoid space.

Animals↗

PubMed1997

Phosphonates as 31P-NMR markers of extra- and intracellular space and pH in perfused rat liver.

We evaluated phosphonates (Po) as markers of the extra- and intracellular space in perfused rat liver. (i) In- and outwash behaviour of phenylphosphonate (PhePo), 3-amino-propylphosphonate (NProPo) and methyl phosphonate (MePo) was compared with that of creatine phosphate (CrP), a marker of the extracellular space, and of dimethyl methylphosphonate (MePoMe2), a marker of the total water-accessible space. In- and outwash of CrP was accurately predicted by the time constant (approximately 12 s) for the in- and outwash of inulin, a standard marker of the extracellular space. MePoMe2 rapidly distributed over the total liver volume (about three times the CrP accessible space). PhePo, NProPo and MePo washed rapidly into the extracellular space with CrP, and then steadily spilled over into the MePoMe2-accessible space. Upon outwash, Po signals rapidly declined in phase with that of CrP. Residual Po (PhePo >> NProPo approximately equal to MePo) reflected the amount internalized during prolonged (60 min) inwash. Proportional amounts of residual Po were found in extracts of livers harvested after outwash of perfusate and extracellular markers. Consistent with exclusion from the cells, CrP went undetected in these extracts. (ii) The resonance frequency of residual PhePo after outwash of the extracellular fraction corresponded with the pH reported by cytosolic P1 and responded to transient changes of the intracellular pH, induced by perfusion with and withdrawal of 20 mM NH4Cl. (iii) MePoMe2 homogeneously distributed over perfusate, parenchyma and bile, consistent with unrestricted permeability. Other Po were transported transcellularly and excreted in bile. CrP was virtually excluded from the bile, attesting to a minimal role for 'bulk-phase pinocytotic' transcellular transport, or for 'paracellular' leakage. In summary, charged Po can be used as extracellular markers in liver, provided experimental conditions are adjusted to minimize their internalization. Some Po (e.g. PhePo) can reach intracellular concentrations which suffice for the compound to act as a reporter molecule of the cytosolic pH.

Animals↗

PubMed2001

Extracellular apparent diffusion in rat brain.

The apparent diffusion coefficients (ADCs) of a series of markers concentrated in the extracellular space of normal rat brain were measured to evaluate, by inference, the ADC of water in the extracellular space. The markers (mannitol, phenylphosphonate, and polyethylene glycols) are defined as "compartment selective" because tissue culture experiments demonstrate some leakage into the intracellular space, making them less "compartment specific" than commonly believed. These primarily extracellular markers have ADCs similar to those of intracellular metabolites of comparable hydrodynamic radius, suggesting that water ADC values in the intra- and extracellular spaces are similar. If this is the case, then it is unlikely that a net shift of water from the extra- to the intracellular space contributes significantly to the reduction in water ADC detected following brain injury. Rather, this reduction is more likely due primarily to a reduction of the ADC of intracellular water associated with injury.

Analysis of Variance↗

PubMed1988

Lactate production and release in cultured astrocytes.

Intracellular lactate content and release of lactate into the surrounding medium of mouse astrocytes in primary culture was measured using the lactate dehydrogenase method. During culturing the cellular content of astrocytes decreased from 400 to 200 nmol/mg protein. The total lactate released into the extracellular space, however, amounted to 75,000 nmol/mg within 98 h, corresponding to a lactate concentration of 10 mM in the cell culture dish. In another set of experiments, cytotoxic swelling was evoked by exposure of the cells to 60 mM K+, this situation caused a 40% increase in cellular volume and an increase in the KCl content of astrocytes. Within 3 h of a change to 60 mM K+ the intracellular lactate content was increased by 100 nmol/mg (one third) and the lactate release in the extracellular space by about 2000 nmol/mg (twice as high as during exposure to 3 mM K+). However, due to the increased intracellular water content, the lactate concentration inside the cells remained unchanged. It is concluded that astrocytes produce substantial amounts of additional lactate during cytotoxic swelling. This lactate, however, is not increasing the intracellular osmolarity and most of the lactate is released into the extracellular space. Depending on the transmembrane transport mechanism it could have the capability to decrease the strong ion difference and contribute to acid shifts in the extracellular space.

Animals↗

PubMed2005

Increase of Cardiotrophin-1 immunoreactivity in regenerating and overloaded but not denervated muscles of rats.

The original report by Pennica et al. on Cardiotrophin-1 (CT-1) states that it markedly stimulates hypertrophy in cardiac myocytes both in vitro and in vivo and is predominantly expressed in the early mouse embryonic heart tube. CT-1 is a member of the interleukin-6 superfamily and past studies have shown that it exerts trophic effects on neurons, glial cells and their precursors, and is expressed during myogenesis. Thus CT-1 is associated with physical and pathological changes in skeletal muscle. In this study, we examined whether CT-1 is expressed in mechanically overloaded, regenerating, and denervated muscles of rats using immunohistochemistry. In the overloaded plantaris muscles at 1 and 3 days postsurgery, CT-1 immunoreactivity was detected in the mononuclear cells that had infiltrated the extracellular space. CT-1 immunoreactivity was also observed in the mononuclear cells invading the extracellular space at 2, 4, and 6 days after a bupivacaine injection and in degenerative and necrotic muscle fibers at 2 days postinjection. In the denervated muscles, the CT-1 immunoreactivity did not change in intensity during the entire period of the denervation (2, 7, and 14 days postsurgery). The cells invading extracellular space and in necrotic muscle fibers possessing CT-1 immunoreactivity might be muscle precursor cells (satellite cells) or migrating macrophages undergoing phagocytosis. Using double-immunostainings for anti-CT-1/antic-met, anti-CT-1/ anti-M-cadherin, and anti-CT-1/anti-ED1, we found that satellite cells and macrophages exhibited CT-1 immunoreactivity in the damaged muscles after bupivacaine injection. We therefore believe that CT-1 plays a key role in regeneration and hypertrophy in the skeletal muscle of rats.

Anesthetics, Local↗

PubMed1972

Age changes in the neuronal microenvironment.

The extracellular space of the rat brain was visualized by electron roscopy in sections of cerebral cortex fixed by freeze-substitution. The volume tissue occupied by the extracellular space was estimated stereomnetrically, and found to decrease from 20.8 percent in 3-month-old rats to 9.6 percent in escent animals, 26 months of age. This decrease in extracellular space indicates age-associated change in the microenvironment of nerve cells.

Aging↗

PubMed1978

Bicarbonate exchange between body compartments after changes of temperature in the larger spotted dogfish (Soyliorhinus stellaris).

Intracellular/extracellular and extracellular/sea-water bicarbonate exchanges were measured in Larger Spotted Dogfish (Sycliorhinus stellaris) exposed to 10 degrees C temperature step changes in a closed sea-water recirculation system. Changes of the bicarbonate concentration in blood plasma (= extracellular space) and in the recirculating sea-water were monitored for 36 h after the temperature change. Intracellular/extracellular transfer of bicarbonate was computed from bicarbonate changes in the extracellular space and sea-water. When the temperature was changed from 10 to 20 degrees C a signigicant transfer of bicarbonate was observed from the intracellular to the extracellular compartment and from the extracellular compartment to the sea-water. These transfers were reversed when the temperature was lowered from 20 to 10 degrees C. The exchange processes were practically completed after 18 h. The amount of bicarbonate exchanged between intracellular and extracellular compartments and sea-water was larger than predicted on the basis of in vitro buffer values of white, red and heart muscle, suggesting that additional tissues exchange significant amounts of bicarbonate with the extracellular space. It is concluded that physicochemical buffering is not sufficient to account for the observed adjustment of intracellular and extracellular pH and that bicarbonate exchange between body compartments and environment may be the most important regulatory mechamism, responsible for the final adjustment of acid-base balance in dogfish.

Acid-Base Equilibrium↗

PubMed1990

Mechanism of potassium uptake in neuropile glial cells in the central nervous system of the leech.

1. Ion-selective double-barreled microelectrodes (ISME) were used to measure intracellular K+ (aKi), Na+ (aNai), and Cl- (aCli) activities of neuropile glial (NG) cells in the central nervous system of the medicinal leech Hirudo medicinalis. Ion fluxes were induced by an increase in extracellular K+ concentration [( K+]o) and analyzed to elucidate the ionic mechanism of the K+ uptake occurring under such conditions. 2. In addition, the K+ concentration of the extracellular space of the nerve cell body region (NCBR) and the neuropile (N) was measured with neutral carrier K(+)-ISME. In normal saline (4 mM K+), a concentration of 4.2 mM was measured in both extracellular spaces. No differences between the K+ concentration of the bathing fluid and the extracellular spaces were found at higher (i.e., 10 and 40 mM) K+ concentrations. 3. In normal saline, the mean membrane potential (Em) was -68 mV, and the mean aKi, aNai, and aCli were found to be 77, 10, and 7 mM, respectively. The corresponding equilibrium potentials were -81, 56, and -66 mV. The chloride equilibrium potential (ECl) was similar to Em, and it is concluded that chloride is passively distributed across the NG cell membrane. 4. When [K+]o was transiently increased 10-fold (i.e., to 40 mM), aKi and a Cli increased transiently by 22 and 25 mM, respectively, and the membrane depolarized to -28 mV, which was similar to both K+ equilibrium potential (EK) and ECl. The KCl uptake was accompanied by a transient decrease in aNai to 5 mM. 5. After incubation for at least 1 h in Na(+)-free saline, NG cells accumulated K+ in the absence of extracellular Na+ to levels similar to those observed in the presence of Na+. Therefore the uptake of K+ was not dependent on external--and probably also internal--Na+. 6. Changes in cell volume induced by the increase in [K+]o were estimated by loading NG cells with choline and monitoring its intracellular concentration with Corning-K(+)-ISME. In saline containing 40 mM K+, NG cell volume increased to approximately 150% of its volume in normal saline. 7. It is concluded that the mechanism of K+ uptake in NG cells is by passive KCl and water influx, which causes cell swelling.

Animals↗

PubMed1995

Cranial meninges of goldfish: age-related changes in morphology of meningeal cells and accumulation of surfactant-like multilamellar bodies.

In the optic tectum of goldfish, the outer, middle and inner layers of the endomeninx were evident in animals ranging in age from 1 month to several years. The outer layer in young animals consisted of closely overlapping cells with intertwined processes, whereas in the older animals it contained large extracellular spaces. The intermediate layer cells were always arranged in a single continuous layer, but in young animals they overlapped extensively with one another toward their edges whereas in the oldest animals they became extremely flat and non-overlapping. The inner layer included an outer tier of cells with their bases adhering to the intermediate layer, and an inner tier of cells detached from both the intermediate layer and the basal lamina overlying the brain parenchyma. Inner layer cells contained many large vacuoles that were in continuity with the extracellular space. With age, the extracellular space and the vacuolar system expanded, and the inner layer evolved into a meshwork of attenuated cytoplasmic processes embedded in the granular extracellular matrix. Another age-related feature was the accumulation adjacent to the basal lamina of uniform disc-shaped membranous structures, resembling multilamellar bodies of lung surfactant. These "disc bodies" were apparently generated by the coalescence of vesicles formed at the surface of the inner layer cells, possibly as a by-product of protein secretion by these cells.

Aging↗

PubMed1994

Extracellular iron chelators protect kidney cells from hypoxia/reoxygenation.

Iron is an important contributor to reoxygenation injury because of its ability to promote hydroxyl radical formation. In previous in vivo studies, we demonstrated that iron chelators that underwent glomerular filtration provided significant protection against postischemic renal injury. An in vitro system was employed to further characterize the protection provided by extracellular iron chelators. Primary cultures of rat proximal tubular epithelial cells were subjected to 60 min hypoxia and 30 min reoxygenation (H/R). During H/R, there was a 67% increase in ferrozine-detectable iron in cell homogenates and increased release of iron into the extracellular space. Cells pretreated with either deferoxamine (DFO) or hydroxyethyl starch-conjugated deferoxamine (HES-DFO), an iron chelator predicted to be confined to the extracellular space, were greatly protected against lethal cell injury. To further localize the site of action of DFO and HES-DFO, tracer quantities of 59Fe were added to DFO or HES-DFO, and their distribution after 2 h was quantitated. Less than 0.1% of DFO entered the cells, whereas essentially none of the HES-DFO was cell-associated. These findings suggest that iron was released during hypoxia/reoxygenation and caused lethal cell injury. Iron chelators confined to the extracellular space provided substantial protection against injury.

Animals↗