Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EXTRACELLULAR SPACE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,423 records · Page 79Linked to original sources
PubMed1978

[Pathobiochemical aspects of lysosomal enzymes with special reference to lysosomal storage diseases (author's transl)].

Lysosomal hydrolases participate substantially in the degradation of all classes of biological macromolecules. They act physiologically within the lysosome. The enzymes are either primarily included within primary lysosomes or are transported to these cell organelles after secretion and subsequent adsorptive pinocytosis. The involvement of these enzymes in a variety of pathological conditions can be understood on the basis of the known functions of lysosomal hydrolases. Inactivity of one or several of the enzymes causes lysosomal storage disorders. Similar metabolic consequences are found when the enzymes are unable to be concentrated within the lysosome. Lysosomal hydrolases participate, furthermore, in the pathogenesis of numerous diseases. A distinction can be made between lysosomal overload, pathologically-increased enzyme secretion into the extracellular space, and a release of lysosomal enzymes into the cytosol.

Acid Phosphatase↗
PubMedDate not supplied

Gross body composition changes in patients with cancer of the uterine cervix treated with irradiation.

Gross body composition studies done on a group of 11 women with cervical cancer before and after completion of radiotherapy revealed moderate compositional changes. There was after irradiation a tendency towards weight loss, connected with some increase of relative total body water content and also its extracellular fraction. The weight loss was due to a decrease of body fat and cell mass, whereas extracellular spaces tended to increase. There was a tendency towards a drop in plasma sodium concentration and an increase of its total content in extracellular water. A significant drop of the potassium serum concentration was observed.

Adult↗
PubMed1983

Extracellular matrix distribution during neocortical wall ontogenesis in "normal" and "Reeler" mice.

The spatio-temporal distribution of extracellular spaces (ECS) was analysed during prenatal corticogenesis in the normal mouse or in the recessive mutant Reeler. Colloidal iron was used to visualize extracellular anionic substances (containing glycosaminoglycans) which constitute an extracellular matrix (ECM). The spatio temporal distribution of the ECM appeared closely related to ECS localization. Before the cortical plate formation, the ECM occurred only in the marginal zone. The plate appearance resulted in a redistribution of anionic sites in the subplate of the normal mouse in addition to the marginal zone. Although, in the Reeler, the ECM remained mainly located in a broad outer cortical zone. Until birth, the distribution of the ECM in the normal mouse, followed closely the inside-out gradient of cortical neuropile maturation, while in the Reeler and outside-in gradient was observed. With EM, following standard fixation and staining an extracellular matrix (formed of 5 to 10 nm fibrils) occurred in sites where the ECM was already detected with light microscopy. The ECM fibrils were seen mainly in the vicinity of young neurons showing characters of secretory functions, such as dilated RER cisternae filled with a fibrillar material and well developed golgi complexes. Young Cajal-Retzius cells appeared especially well suited to elaborate the ECM in the marginal zone of the normal mouse or in the outer cortical zone of the Reeler. The potential role of ECM for the differentiation and formshaping of young neurons is discussed.

Animals↗
PubMed1993

[Cerebral microdialysis in neurological and neurosurgical research and clinical application in neurology and neurosurgery].

Microdialysis of the cerebral extracellular space (CES) provides information on the cortical metabolic state by measurement of the concentrations of metabolites and transmitters as well as of the extracellular pH. In trauma patients, this kind of monitoring should reveal damage from secondary cortical ischemia in an early, hopefully reversible state. The method further allows in vivo measurement of drug levels in the CES and investigation of their effect on metabolism. Although microdialysis has mainly been used experimentally, it is now beginning to be applied clinically. We report on our experience with both experimental and clinical work.

Animals↗
PubMed1978

Uptake of tolbutamide by islets of Langerhans and other tissues.

3-H-tolbutamide was distributed in a volume exceeding the space occupied by 14-C-sucrose in islets as well as in liver, kidney, muscle, and fat. In contrast to previous reports, the findings suggest that tolbutamide is not restricted to the extracellular space of islets.

Adipose Tissue↗
PubMed2006

Proteolytic regulatory mechanisms in the formation of extracellular morphogen gradients.

Growth factors are secreted into the extracellular space, where they encounter soluble inhibitors, extracellular matrix glycoproteins and proteoglycans, and proteolytic enzymes that can each modulate the spatial distribution, activity state, and receptor interactions of these signaling molecules. During development, morphogenetic gradients of these growth factors pattern fields of cells responsive to different levels of signaling, creating such structures as the branched pattern of airways and vasculature, and the arrangement of digits in the hand. This review focuses specifically on the roles of proteolytic enzymes and their regulators in the generation of such activity gradients. Evidence from Drosophila developmental pathways provides a detailed understanding of general mechanisms underlying proteolytic control of morphogen gradients, while recent studies of several mammalian growth factors illustrate the relevance of this proteolytic control to human development and disease.

Animals↗
PubMed1992

Effect of extracellular calcium concentration on angiotensin AT1 receptor-mediated smooth muscle contraction and antagonism in rabbit aorta.

Angiotensin-II (AII) stimulates smooth muscle contraction by activating angiotensin AT1 receptor which induces intracellular Ca2+ release and Ca2+ influx from extracellular space. In this study, effect of extracellular Ca2+ concentration ([Ca2+]0) on angiotensin AT1 receptor-mediated contractile response to AII has been examined in the absence and presence of [Sar1,Ala8]AII in rabbit aorta. A decrease in agonist potency and an increase in antagonist potency for depression were observed in low [Ca2+]0. Data were interpreted by applying an explanatory model developed previously. The result indicates that [Ca2+]0 is linked to the efficacy expression of AII at angiotensin AT1 receptor and this prompted speculation about the underlying mechanism.

Angiotensin II↗
PubMed1998

Dexamethasone augments ischemia-induced extracellular accumulation of glutamate in gerbil hippocampus.

Glucocorticoids exacerbate neuronal damage due to hypoxia, ischemia, seizure and hypoglycemia. Because the release of glutamate is closely involved in neuronal damage, the effects of dexamethasone on the ischemia-induced accumulation of extracellular amino acids (aspartate, glutamate, and glycine) were investigated in the gerbil hippocampal CA1 region by a microdialysis-high-performance liquid chromatography procedure in vivo. There were no differences in the extracellular concentrations of amino acids before ischemia between the control group and the dexamethasone (3m microg, i.c.v.)-injected group. The concentration of glutamate reached 246% of that before ischemia within 2.5 min of transient forebrain ischemia. Dexamethasone augmented the increase in glutamate to 508% of that before ischemia. This finding suggests that glucocorticoids aggravate ischemic neuronal damage by causing glutamate to accumulate in the extracellular space.

Animals↗
PubMed1999

Extracellular glutamate in the dorsal horn of the lumbar spinal cord in the freely moving rat during hindlimb stepping.

The capacity to reestablish locomotor function after complete spinal cord transection in the adult mammal is now well documented. Further studies have shown different neurotransmitters to be involved in the initiation and maintenance of these locomotor patterns. However, there has been no in vivo evidence of the changes in glutamate or any other neurotransmitter in the extracellular space of the dorsal horn during an alternating motor pattern such as hindlimb stepping. This study describes an in vivo microdialysis technique to measure extracellular glutamate in the dorsal horn of the spinal cord in the fully awake intact rat. A concentric microdialysis probe was placed in the dorsal horn at L5, and 18 h later dialysate samples were collected at 20-min intervals before, during, and after 20 min of hindlimb stepping. During stepping, extracellular glutamate rose 150% above resting levels and returned to resting levels 40 min later. This increase may have occurred either as a result of primary afferent depolarization or modulation by the descending and ascending supraspinal pathways. In another series of experiments extracellular glutamate was, therefore, measured in the dorsal horn of the chronic spinally transected rat during 20 min of hindlimb stepping. Although the spinal group did not take as many steps as the intact group, those taking more than 40 steps showed a significant rise in extracellular glutamate, and the number of steps taken by the individual spinal rats correlated positively with the individual values of extracellular glutamate (r2 = 0.63). These results are consistent with glutamate being an important neurotransmitter in the spinal cord in normal locomotion.

Animals↗
PubMed2001

Closed head injury increases extracellular levels of antioxidants in rat hippocampus in vivo: an adaptive mechanism?

Reactive oxygen species (ROS) are a major cause of secondary brain injury following head trauma. Low molecular weight antioxidants (LMWA) protect the tissue against oxidative damage caused by ROS. In the present study, we measured the extracellular levels of the LMWA ascorbic acid and uric acid in the rat brain before, during and after experimental closed head injury (CHI). A dialysis probe was inserted into the right ventral hippocampus through a chronically implanted guide. CHI was applied to the left hemisphere using a weight-drop device. CHI induced a rapid but transient increase in ascorbic acid levels. Uric acid levels increased to 250% of baseline shortly after CHI and remained elevated at 2 h after CHI. Previous results show that the overall reducing power of brain tissue decreases following CHI. Together with previous results, the current findings suggest that ascorbic acid and uric acid are mobilized from brain cells to the extracellular space.

Animals↗
PubMed2000

Wingless gradient formation in the Drosophila wing.

BACKGROUND: Secreted signaling proteins of the Wingless (Wg)/Wnt, Hedgehog and bone morphogenetic protein (BMP)/Decapentaplegic (Dpp) families function as morphogens to control growth and pattern formation during development. Although these proteins have been shown to act directly on distant cells in the developing limbs of the fruit fly Drosophila, little is known about how ligand gradients form in vivo. Wg protein is found in vesicles in Wg-responsive cells in the embryo and imaginal discs. It has been proposed that Wg may be transported by a vesicle-mediated mechanism. RESULTS: A novel method to visualize extracellular Wg protein was used to show that Wg forms an unstable gradient on the basolateral surface of the wing imaginal disc epithelium. Wg movement did not require internalization by dynamin-mediated endocytosis. Dynamin activity was, however, required for Wg secretion. By reversibly blocking Wg secretion, we found that Wg moves rapidly to form a long-range extracellular gradient. CONCLUSIONS: The Wg morphogen gradient forms by rapid movement of ligand through the extracellular space, and depends on continuous secretion and rapid turnover. Endocytosis is not required for Wg movement, but contributes to shaping the gradient by removing extracellular Wg. We propose that the extracellular Wg gradient forms by diffusion.

Animals↗
PubMedDate not supplied

Improvement in enzyme productivities from mold cultivations using the liquid-phase oxygen supply strategy.

Cultivations of Aspergillus niger cells in which oxygen was provided through the liquid-phase oxygen supply strategy (which involves the need-based decomposition of H2O2 pulses to yield the necessary oxygen) were studied. Concentrations of H2O2 in the range of 1 to 5 mM were found to be suitable for use in cultivations. The growth rate constant of 0.17 h(-1) obtained in the H2O2-based cultivation, was comparable to that obtained in the cultivation with aeration; however, the maximum cell concentration in the H2O2-based cultivation was 124% of that obtained in cultivation with aeration. Maximum concentrations of catalase, protease and glucose oxidase obtained in the H2O2-based cultivation, were 240%, 172%, and 124% respectively, of those obtained in the cultivation with aeration. Further, the specific enzyme levels (units per gram cell) of catalase and protease obtained in the H2O2-based cultivation were 172% and 156% of those obtained in the cultivation with aeration, whereas, the specific glucose oxidase levels were comparable. In addition, the oxygen profiles inside the pellets ofA. niger during both the modes of oxygen supply were described using mathematical models. Studies to elucidate the mechanism of oxygen availability showed that the decomposition of the H2O2 supplied in the extracellular space occurred intracellularly, as well as extracellularly, to yield oxygen. Also, the proton motive force (PMF) was found to be involved in the process of oxygen availability from H2O2 to A. niger cells.

Aspergillus niger↗
PubMed2001

Differing effects of substrate and non-substrate transport inhibitors on glutamate uptake reversal.

Na(+)-dependent excitatory amino acid transporters (EAATs) normally function to remove extracellular glutamate from brain extracellular space, but EAATs can also increase extracellular glutamate by reversal of uptake. Effects of inhibitors on EAATs can be complex, depending on cell type, whether conditions favor glutamate uptake or uptake reversal and whether the inhibitor itself is a substrate for the transporters. The present study assessed EAAT inhibitors for their ability to inhibit glutamate uptake, act as transporter substrates and block uptake reversal in astrocyte and neuron cultures. L-threo-beta-hydroxyaspartate (L-TBHA), DL-threo-beta-benzyloxyaspartate (DL-TBOA), L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-2,4-PDC) (+/-)-cis-4-methy-trans-pyrrolidine-2,4-dicarboxylic acid (cis-4-methy-trans-2,4-PDC) and L-antiendo-3,4-methanopyrrolidine-2,4-dicarboxylic acid (L-antiendo-3,4-MPDC) inhibited L-[14C]glutamate uptake in astrocytes with equilibrium binding constants ranging from 17 microM (DL-TBOA and L-TBHA) - 43 microM (cis-4-methy-trans-2,4-PDC). Transportability of inhibitors was assessed in astrocytes and neurons. While L-TBHA, L-trans-2,4-PDC, cis-4-methy-trans-2,4-PDC and L-antiendo-3,4-MPDC displayed significant transporter substrate activities in neurons and astrocytes, DL-TBOA was a substrate only in astrocytes. This effect of DL-TBOA was concentration-dependent, leading to complex effects on glutamate uptake reversal. At concentrations low enough to produce minimal DL-TBOA uptake velocity (< or = 10 microM), DL-TBOA blocked uptake reversal in ATP-depleted astrocytes; this blockade was negated at concentrations that drove substantial DL-TBOA uptake (> 10 microM). These findings indicate that the net effects of EAAT inhibitors can vary with cell type and exposure conditions.

ATP-Binding Cassette Transporters↗
PubMed2000

Epitope-tagged P(0) glycoprotein causes Charcot-Marie-Tooth-like neuropathy in transgenic mice.

In peripheral nerve myelin, the intraperiod line results from compaction of the extracellular space due to homophilic adhesion between extracellular domains (ECD) of the protein zero (P(0)) glycoprotein. Point mutations in this region of P(0) cause human hereditary demyelinating neuropathies such as Charcot-Marie-Tooth. We describe transgenic mice expressing a full-length P(0) modified in the ECD with a myc epitope tag. The presence of the myc sequence caused a dysmyelinating peripheral neuropathy similar to two distinct subtypes of Charcot-Marie-Tooth, with hypomyelination, altered intraperiod lines, and tomacula (thickened myelin). The tagged protein was incorporated into myelin and was associated with the morphological abnormalities. In vivo and in vitro experiments showed that P(0)myc retained partial adhesive function, and suggested that the transgene inhibits P(0)-mediated adhesion in a dominant-negative fashion. These mice suggest new mechanisms underlying both the pathogenesis of P(0) ECD mutants and the normal interactions of P(0) in the myelin sheath.

Animals↗
PubMed2005

Spontaneously immortalized mouse embryo fibroblasts: growth behavior of wild-type and vimentin-deficient cells in relation to mitochondrial structure and activity.

Dependent on the presence or absence of vimentin, primary mouse embryo fibroblasts exhibit different growth characteristics in vitro. While most Vim(+/+) fibroblasts stop dividing and die via apoptosis, a substantial fraction of cells immortalize and proliferate almost normally. Vim(-/-) fibroblasts cease to divide earlier, immortalize in vanishingly small numbers and thereafter proliferate extremely slowly. Early after immortalization, Vim(+/+) (imm) fibroblasts appear structurally almost normal, whereas Vim(-/-) (imm) fibroblasts equal postmitotic "crisis" cells, which are characterized by increased cell size, altered cell ultrastructure, nuclear enlargement, genome destabilization, structural degeneration of mitochondria, and diminution of mitochondrial respiratory activity. The differences between immortalized Vim(+/+) (imm) and Vim(-/-) (imm) fibroblasts persist during early cell cloning but disappear during serial subcultivation. At high cell passage, cloned, immortalized vim(-) fibroblasts grow nearly as fast as their cloned vim(+) counterparts, and also resemble them in size, ultrastructure, nuclear volume, and mitochondrial complement; they very likely employ redundancy to cope with the loss of vimentin function when adjusting structure and behavior to that of immortalized vim(+) fibroblasts. Reduction in nuclear size occurs via release of large amounts of filamentous chromatin into extracellular space; because it is complexed with extracellular matrix proteins, it tends to form clusters and to tightly stick to the surface of other cells, thus providing a potential for horizontal gene transfer. On the other hand, cloned vim(+) and vim(-) fibroblasts are equal in showing contact inhibition at young age and becoming anchorage-independent during serial subcultivation, as indicated by the formation of multilayered and -faceted cell sheets and huge spheroids on top of or in soft agar. With this, immortalized vim(-) fibroblasts reduce their adhesiveness to the substratum which, in their precrisis state and early after cloning, is much higher than that of their vim(+) counterparts. In addition, the coupling between the mitochondrial respiratory chain and oxidative phosphorylation is stronger in vim(+) than vim(-) fibroblasts. It appears from these data that after explantation of fibroblasts from the mouse embryo the primary cause of cell and mitochondrial degeneration, including genomic instability, is the mitochondrial production of reactive oxygen species in a vicious circle, and that vimentin provides partial protection from oxidative damage. As a matrix protein with specific in vitro and in vivo affinities for nuclear and mitochondrial, recombinogenic DNA, it may exert this effect preferentially at the genome level via its influence on recombination and repair processes, and in this way also assist the cells in immortalizing. Additional protection of mitochondria by vimentin may occur at the level of mitochondrial fatty acid metabolism.

Animals↗
PubMed1998

Determination of free interstitial concentrations of piperacillin-tazobactam combinations by microdialysis.

The investigation of tissue penetration and distribution of antibiotics is of great importance, since infections occur mostly in the tissues. The aim of this study was to investigate the pharmacokinetics of piperacillin and tazobactam, alone and in combination, by measuring total plasma and free interstitial concentrations, and to examine the relationship between free levels of both drugs in blood and those in the extracellular space. Piperacillin and tazobactam were administered, alone and in combination, to anaesthetized rats as a single iv bolus dose. Total plasma concentrations and free extracellular concentrations were quantified by HPLC. In-vivo microdialysis sampling was used to study the free tissue distribution patterns of both drugs. The pharmacokinetics of piperacillin and tazobactam in plasma were consistent with a two-compartment body model. Piperacillin pharmacokinetics were not influenced by co-administration of tazobactam. Tazobactam's volumes of distribution and clearance were decreased by the co-administration of piperacillin and the area under the curve was significantly increased. Comparisons between calculated free concentrations in the peripheral compartment for both drugs and measured free extracellular concentrations revealed excellent agreement. For piperacillin and tazobactam, alone and in combination, predictions of the concentration-time profiles of free drug in the peripheral compartment can be made on the basis of plasma data.

Animals↗
PubMed1997

The effect of halothane on the recirculatory pharmacokinetics of physiologic markers.

BACKGROUND: The cardiovascular effects of halothane are well recognized, but little is known of how this affects drug distribution. The effect of halothane anesthesia on physiologic factors that affect drug disposition from the moment of injection was investigated. METHODS: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1%, 1.5%, and 2% halothane in a randomized order determined by a repeated measures Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on frequent early and less frequent later arterial blood samples. These models characterize the role of cardiac output and its distribution on drug disposition. RESULTS: Halothane caused a significant and dose-dependent decrease in cardiac output. The disposition of antipyrine was most profoundly affected by halothane anesthesia, which increased both nondistributive intercompartmental clearance and volume while decreasing fast and slow tissue clearances and elimination clearance in a halothane dose-dependent manner. CONCLUSIONS: Halothane-induced changes in blood flow to the compartments of the antipyrine recirculatory model were not proportional to changes in cardiac output. Halothane anesthesia significantly increased (to more than double) the area under the drug concentration versus time curve due to an increase in the apparent peripheral blood flow not involved in drug distribution, despite a dose-dependent cardiac output decrease. Recirculatory pharmacokinetic models include the best aspects of traditional compartmental and physiologic pharmacokinetic models while offering advantages over both.

Anesthesia, Inhalation↗
PubMed2000

Isoflurane alters the recirculatory pharmacokinetics of physiologic markers.

BACKGROUND: Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution. METHODS: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition. RESULTS: Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered. CONCLUSIONS: The isoflurane-induced changes in marker disposition were different than those the authors reported previously for halothane anesthesia, volume loading, or hypovolemia. These data provide further evidence that not only cardiac output but also its peripheral distribution affect early drug concentration history after rapid intravenous administration.

Anesthetics, Inhalation↗