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At least 1,621 records · Page 90Linked to original sources
PubMed1998

Proteoglycans in human coronary arteriosclerotic lesions.

Proteoglycans in human coronary arteries were characterized immunohistochemically, using specific monoclonal antibodies to distinct proteoglycan types. In addition, apoB, macrophage, and arterial smooth muscle cell alpha-actin markers were localized. The expression of chondroitin sulfate proteoglycans and apoB was observed in healthy areas (operationally defined by morphology) as well as in lesions in the intima, but with greater expression in the atheromatous lesions. In healthy intima heparan sulfate proteoglycan was cell associated, but in lesions it was found also in the extracellular space. A dermatan sulfate proteoglycan of decorin type was not observed in the healthy intima but was observed in the intima with adaptive thickening especially in zones with reduced staining for smooth muscle cell alpha-actin. In atheroma (fibrous plaque with necrotic core) decorin along with alpha-actin and macrophage marker stained brightly in the extracellular regions in fibrous cap (actively progressing lesion) but was sparse in fibrous base (quiescent lesion). The observations suggest that decorin along with extracellular alpha-actin and macrophage marker may be useful for differentiating lesions that tend to progress with disease.

Actins↗
PubMed2002

Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts.

Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis. VEGFs are bioactive in the extracellular space where they become available to the endothelial cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one mechanistic explanation to the decreased tumor growth and metastasis.

Animals↗
PubMed1987

Sustained oscillations in extracellular calcium concentrations upon hormonal stimulation of perfused rat liver.

Sustained oscillations in extracellular free Ca2+ were shown to occur on addition of vasopressin, phenylephrine or angiotensin II in isolated rat liver perfused with low (10 microM)-Ca2+ medium. The amplitude and frequency of oscillation depend on hormone concentration. In contrast, Ca2+ releases on addition of ATP, t-butyl hydroperoxide or arachidonate do not exhibit oscillatory behaviour. The vasopressin-induced oscillations were suppressed by glucagon and dibutyryl 3',5'-cyclic AMP, but not by dibutyryl 3',5'-cyclic GMP. These observations in the extracellular space complement observations by Woods, Cuthbertson & Cobbold [(1986) Nature (London) 319, 600-602] on oscillations in intracellular free Ca2+ in single liver cells.

Adenosine Triphosphate↗
PubMed2000

Cardiac fibroblasts express the cAMP-adenosine pathway.

The extracellular "cAMP-adenosine pathway" refers to the local production of adenosine mediated by cAMP egress into the extracellular space, conversion of cAMP to AMP by ectophosphodiesterase, and the metabolism of AMP to adenosine by ecto-5'-nucleotidase. The goal of this study was to assess whether the cAMP-adenosine pathway limits cardiac fibroblast growth. Studies were conducted in ventricular cardiac fibroblasts maintained in 3-dimensional cultures. Addition of exogenous cAMP to cardiac fibroblasts increased extracellular levels of AMP, adenosine, and inosine in a concentration-dependent and time-dependent manner. This effect was attenuated by blockade of total phosphodiesterase activity (3-isobutyl-1-methylxanthine), ectophosphodiesterase activity (high concentration of 1, 3-dipropyl-8-p-sulfophenylxanthine), or ecto-5'-nucleotidase (alpha, beta-methylene-adenosine-5'-diphosphate). Treatment with exogenous cAMP inhibited cell growth as assessed by DNA synthesis ((3)H-thymidine incorporation), cell proliferation (cell counts), and protein synthesis ((3)H-leucine incorporation). Antagonism of A(2) (KF17837) or A(1)/A(2) (low concentration of 1, 3-dipropyl-8-p-sulfophenylxanthine), but not A(1) (8-cyclopentyl-1, 3-dipropylxanthine), adenosine receptors blocked the growth-inhibitory effects of exogenous cAMP, but not the growth inhibitory effects of 8-bromo-cAMP (stable cAMP analogue). The growth-inhibitory effects of exogenous cAMP were enhanced by the combined inhibition of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl) adenine] and adenosine kinase (iodotubercidin). In conclusion, the extracellular cAMP-adenosine pathway exists in cardiac fibroblasts and attenuates cell growth. Pharmacological augmentation of this pathway could abate pathological cardiac remodeling in heart disease.

1-Methyl-3-isobutylxanthine↗
PubMed1989

[Extracellular concentration of dopamine and dopamine metabolites in the rat striatum during cerebral ischemia and reperfusion].

Many data suggest that the presence of dopamine (DA) is a prerequisite for the development of neuronal damage in the striatum; neural injury could be initiated by a massive release from dopaminergic nerve terminals during ischemia. The current study was undertaken in order to define the mechanism through which ischemia alters dopaminergic neurotransmission, and to examine the subsequent events early during recirculation. Experiments were performed on 14 male anesthetized Sprague Dawley rats. The ischemic insult consisted of 20 min global cerebral ischemia (4-vessel occlusion) followed by 80 min reperfusion. Cardiac arrest concluded this phase of the experiment, but measurements were continued for 60 min more. Measurements of catechols were made in the striatum using in vivo differential pulse voltammetry (DPV), each 4 min, throughout the experiment and for 60 min post-mortem. DPV data were substantiated with intracerebral dialysis; 20 min dialysate samples were analysed for dopamine (DA) and homovanillic acid (HVA; DA metabolite) using high performance liquid chromatography (HPLC). Repeated in vivo DPV measurements of striatal catechols during ischemia/reperfusion were collected in 11 of 14 experiments. In 6 out of 11 rats, ischemia induced a massive catechols release in the striatum, resulting in a marked increase in extracellular level (350 to 1200% of control), which persisted throughout ischemia. In these rats, a marked rise in extracellular DA was detected in the dialysate sample collected in the contralateral striatum during ischemia, together with a fall in HVA, probably due to ischemic inhibition of the enzymatic oxidation of DA. Catechol was cleared from the extracellular space within minutes of reperfusion, indicating functional catechol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Hypoosmolar conditions reduce extracellular volume fraction and enhance epileptiform activity in the CA3 region of the immature rat hippocampus.

The osmolarity of the extracellular space (ECS) compartment is an important factor determining the excitability of neuronal tissue. In the adult hippocampus an important role of osmolarity and ECS diffusion parameters on the susceptibility to epileptic events is well established, but the influence of hypo- and hyperosmolar conditions on the immature hippocampus remains elusive. To investigate the influence of osmolarity on epileptiform activity, extracellular field potentials were recorded in the CA3 region of hippocampal slices of immature (postnatal days 4-7) Wistar rats. The ECS diffusion parameters were determined by the real-time tetramethylammonium (TMA+) iontophoretic method with ion-selective microelectrodes in immature hippocampal slices and showed a lack of diffusion anisotropy; a tortuosity of about 1.39; and a volume fraction, alpha, of 0.41 +/- 0.01 (n = 10 slices). A reduction in osmolarity of -90 mOsm induced a decrease in alpha to 0.17 +/- 0.02 (n = 4 slices). The frequency of epileptiform activity elicited in 10-50 microM 4-AP-containing low-Mg2+ solution was increased under -90 mOsm and -40 mOsm hypoosmolar conditions by 39.9% +/- 8.1% (n = 16) and 24.1% +/- 4.8% (n = 10), respectively, whereas hyperosmolar solutions decreased the frequency. A -90-mOsm reduction in the osmolarity of low-Mg2+ solution induced epileptiform activity in nine of 19 slices. In summary, these results demonstrate that hypoosmolar conditions increased excitability and susceptibility to epileptiform activity in immature hippocampal slices, suggesting a functional role of the larger alpha in suppression of seizures.

4-Aminopyridine↗
PubMed1990

Quantitation of blood plasma DNA as an index of in vivo cytotoxicity.

Cell death triggers the release into extracellular spaces of products of chromatin catabolism, particularly of DNA. A sensitive DNA assay has been used to investigate in the mouse whether the quantitation of plasma DNA may be used as an index of in vivo cytotoxicity. It has been found that toxic doses of bacterial lipopolysaccharide, HgCl2, CCl4, cyclophosphamide and hydroxyurea, are responsible for the release of extracellular DNA in plasma, in a dose dependent relationship. In conclusion, quantitation of extracellular DNA may be used for investigating in vivo cell death phenomena induced by toxic agents and drugs. Such a method could be applied to toxicological studies in animals and man.

Animals↗
PubMed1995

Activity-induced Ca2+ transients in nerve and glial cells in the leech CNS.

We have measured activity-induced Ca2+ transients in Retzius neurones, neuropile glial cells, and extracellular spaces of isolated ganglia of the leech Hirudo medicinalis using the fluorescent dye fura-2 and Ca(2+)-sensitive microelectrodes. Neuronal activity, induced by electrical side nerve stimulation (20 Hz/1 min), elicited transient rises of intracellular Ca2+ in both neurones and glial cells, which amounted to 24 +/- nM (n = 15) and 17 +/- 14 nM (n = 7), respectively. The extracellular Ca2+ declined by 160 +/- 73 microM (n = 6) during stimulation. Intra- and extracellular Ca2+ transients were reduced by the glutamate/kainate receptor blocker CNQX (6-cyano-7-dinitroquinozaline-2,3-dione; 50 microM). Our results show that neuronal activity evokes Ca2+ signals not only in neurones, but also in glial cells and suggest that these Ca2+ transients are partly mediated via activation of glutamate/kainate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Muscarinic receptor-mediated increase in extracellular inositol 1,4,5-trisphosphate levels in the rat hippocampus: an in vivo microdialysis study.

The extracellular concentration of inositol 1,4,5-trisphosphate (IP3) has been monitored in the ventral hippocampus of the anesthetized rat by using a microdialysis technique coupled to a radioreceptor assay. Three hours after the implantation of the cannula, basal extracellular concentration of IP3 (corrected for a 9% recovery) was 71 nM (0.39 pmol/60-microliters fraction) and remained stable for at least 5 h. Local infusion of carbachol for 60 min caused a significant concentration-related increase in extracellular IP3 levels (0, 24, and 57% at 1, 50, and 100 microM, respectively). Acetylcholine (100 microM) and muscarine (100 microM) increased IP3 outflow by 40 and 42%, respectively. The effect of carbachol was fully prevented by coinfusion of 10 microM pirenzepine and reduced by 1 microM tetrodotoxin indicating that the carbachol response is mediated by neuronal muscarinic receptors. These data demonstrate the feasibility of using microdialysis and a radioreceptor assay to measure IP3 in the extracellular space. This approach could prove useful for the study of the in vivo operation of muscarinic and, by extension, a number of receptors coupled to phosphoinositide turnover.

Animals↗
PubMed1970

Solvent water for electrolytes in the muscle fiber of the giant barnacle.

Seven experiments are described which permit estimation of the "solvent water" or the "osmotically active water" of the dissected fiber from the giant barnacle, Balanus nubilus. Each of the first four experiments includes the measurement of a free ion activity in the myoplasm by means of a Na(+), K(+), or Cl(-) ion-specific microelectrode. The fifth experiment makes use of a membrane potential vs. [K](o) curve. The last two experiments measured fiber water and fiber volume as bath osmolarity was changed. The seven independent estimations of solvent water ranged from 0.64 to 0.72 of fiber water with a mean of 0.68. Since the extracellular space of single fibers was about 7% of fiber water, it was concluded that 25% of analyzable water was not acting as solvent for the osmotically active solutes in the myoplasm.

Animals↗
PubMed1987

Sources and sinks of light-evoked delta [K+]o in the vertebrate retina.

In the vertebrate retina, recordings of light-evoked changes in extracellular K+ concentration delta [K+]o are of particular interest because this tissue is complex and multilayered, yet can be activated routinely with its "natural" stimulus (i.e., light). This review identifies the components of the spatiotemporal profile of retinal light-evoked delta [K+]o and then presents evidence concerning the specific neural origins of these components as well as the mechanisms by which these delta [K+]o are dispersed from extracellular space. Finally, to gain improved resolution of K+ sources and sinks, the technique of ion source density is introduced and applied to both model and real spatiotemporal distributions of delta [K+]o.

Animals↗
PubMed1984

Release of endogenous catecholamines in the ischemic myocardium of the rat. Part B: Effect of sympathetic nerve stimulation.

The contribution of centrally originating sympathetic activity to the myocardial extracellular accumulation of noradrenaline during the early phase of ischemia has been assessed in a perfused (Langendorff) rat heart preparation isolated except for its sympathetic innervation. A 10-minute electrical stimulation (4 Hz, 5 V) of the left cervicothoracic ganglion during normal perfusion causes the overflow of 177.5 +/- 13.7 pmol noradrenaline/g heart, whereas such stimulation during ischemia liberates only 21.5 +/- 3.6 pmol/g (collected during reperfusion). When neuronal reuptake is blocked by desipramine, corresponding values are 321.5 +/- 22.5 pmol/g (normal flow) and 151.8 +/- 22.4 pmol/g (ischemia). After combined blockade of neuronal uptake, extraneuronal uptake, and alpha 2-receptors, nerve stimulation liberates 674 +/- 22 pmol/g during normal flow and 206 +/- 24.3 pmol/g during ischemia. These results suggest that, in vivo, centrally originating neural activity would not lead to substantial accumulation of noradrenaline within the extracellular space of the ischemic myocardium. This failure of accumulation is due to both a functioning neuronal uptake of noradrenaline and a failure of neurotransmission.

Animals↗
PubMed1982

Calcium fluxes in mouse mammary tissue in vitro: intracellular and extracellular calcium pools.

1. The total Ca content of the mammary gland increased from about 2 to 12 mumole/g tissue during the transition from pregnancy to lactation in the mouse. In tissue from lactating mice at least two thirds of the total Ca exchanged with external Ca in 6 hr. There was little non-exchangeable Ca in tissues from pregnant mice.2. At 37 degrees C the time courses of influx and efflux of (45)Ca in lactating tissues could be analysed by assuming three exponential components with rate constants of about 0.3, 0.06 and 0.005 min(-1) and containing, respectively, 1.7, 1.5 and 4.7 mumole (45)Ca/g tissue at the steady state.3. The rapidly effluxing component showed the time- and temperature-dependence characteristic of bulk-phase-limited diffusion through the extracellular space. The diffusion coefficient was about one quarter of the self-diffusion coefficient of Ca in aqueous solution, consistent with a tortuosity factor of about 2. A portion of the Ca in this component was displaced by La(3+). The amount remaining in the presence of 3 mm-La(3+) was close to that expected for free extracellular Ca. The rapid component was therefore interpreted as originating from an extracellular compartment containing both free and bound Ca.4. The rate of efflux of the intermediate component was slowed by a factor of ten when the temperature was decreased from 37 to 0 degrees C giving a Q(10) of 2.7, expected for membrane transport. The slow component present at 37 degrees C was not displaced by EGTA or La(3+), suggesting that it is not localized extracellularly. It was not apparent in the 0 degrees C efflux curves.5. The biphasic time course of uptake of ionophore (A23187)-releasable (45)Ca in particulate fractions obtained by homogenization and centrifugation of tissues which had been incubated with the isotope was consistent with the hypothesis that the two slower components of (45)Ca flux originate from intracellular compartments. Mitochondrial uptake probably did not contribute significantly to Ca exchange in these tissues.6. (45)Calcium fluxes in mammary tissues from pregnant mice also showed three components with rate constants similar to those found in tissues from lactating mice. The amount of Ca in each component was much smaller than in lactating tissue when compared on the basis of tissue weight.7. We conclude from these studies that: (i) intra- and extracellular Ca pools in mammary tissue can be distinguished on the basis of the temperature dependence of their fluxes and (ii) the transition from pregnancy to lactation is accompanied by large increases in both intra- and extracellular Ca pools in mammary alveolar cells.

Animals↗
PubMed1999

Simultaneous measurement of cortical potassium, calcium, and magnesium levels measured in head injured patients using microdialysis with ion chromatography.

Potassium, calcium and magnesium were measured in 3717 microdialysate samples in 43 patients with head injury experiencing refractory increased ICP, episodes of jugular venous oxygen desaturation and brain death. Cation analysis was performed with 'ion chromatography'. Potassium levels remained stable until severe physiological deterioration occurred, whereupon they increased 100-400%, usually associated with release of amino-acids including glutamate, aspartate, and taurine into the extracellular space. The magnesium and calcium levels remained unchanged, regardless of the severity of physiological deterioration.

Brain Injuries↗
PubMed1996

The measurement of extracellular inorganic phosphate gives a more reliable indication for severe impairment of cerebral cell function and cell death than the measurement of extracellular lactate.

The measurement of cerebral extracellular lactate levels has been suggested to be used to monitor cerebral function in intensive care However, although an increase of extracellular lactate levels is a sensitive parameter for increased cellular activity in general, it will be shown that its prognostic value is limited in regard to the severity of the impairment of cellular function. As an alternative the measurement of the extracellular levels of inorganic phosphate (IP) or adenosine is proposed here: Whereas extracellular lactate levels increased rapidly to about the same extents during ischemia (IS) and spreading depression (SD), IP rose during IS only. Adenosine, on the other hand, increased during both events to a different degree. If, therefore, lactate was the only parameter to be monitored after a cerebral insult, the results would not allow to discriminate between a transient, spontaneously recovering event as a SD and a long lasting or an irreversible loss of cell function as in persisting ischemia/hypoxia. The measurement of IP, therefore, seems to be more suitable than that of lactate or adenosine since IP will appear within the extracellular space only after a sustained failure of membrane function. Thus, the measurement of IP changes turned out to be the more useful parameter for intensive care supervision.

Adenosine↗
PubMed1985

Body composition in elderly people. I. Determination of body composition by multiisotope method and the elimination kinetics of these isotopes in healthy elderly subjects.

The body composition of 40 healthy elderly and 20 healthy young subjects was determined and compared. It was found that the age-related changes were more marked in females than in males. Total body water was decreased as a consequence of diminished lean body mass. Extracellular fluid volume remained unchanged, while plasma volume increased. Thus, the liquid components of lean body mass were redistributed between the intracellular and extracellular spaces. The elimination kinetics of isotopes were not significantly different between young and aged subjects, except the elimination of radiosulfate.

Aged↗
PubMed1995

Dissociation of synchronization and excitability in furosemide blockade of epileptiform activity.

Furosemide, a chloride cotransport inhibitor, reversibly blocked synchronized burst discharges in hippocampal slices without reducing the pyramidal cell response to single electrical stimuli. Images of the intrinsic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space. In urethane-anesthetized rats, systemically injected furosemide blocked kainic acid-induced electrical discharges recorded from cortex. These results suggest that (i) neuronal synchronization involved in epileptiform activity can be dissociated from synaptic excitability; (ii) nonsynaptic mechanisms, possibly associated with furosemide-sensitive cell volume regulation, may be critical for synchronization of neuronal activity; and (iii) agents that affect extracellular volume may have clinical utility as antiepileptic drugs.

4-Aminopyridine↗
PubMed1977

Ultrastructural study of a hitherto unknown disturbance of the synthesis of collagen precursor molecules in human cutis.

The ultrastructural characteristics of on hitherto unknown disturbance of collagen precursor molecules in human skin were studied. A severe disturbance of the synthesis of collagen exists at the procollagen stage. The paracrystalline accumulation of a form of procollagen in the tubes of the smooth ER and an increase in its appearance in the extracellular space, distinguish this clinical picture from all other previously described connective tissue disorders, especially from Dermatosparaxis and Ehlers-Danlos syndrome type VII. For this clinical picture we suggest the name "Dermatosparaxis endoplasmatica".

Adult↗