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At least 181 records · Page 10Linked to original sources

PubMed1998

Simultaneous microdialysis in brain and blood of the mouse: extracellular and intracellular brain colchicine disposition.

A simultaneous brain and blood microdialysis system was developed to study the passage of colchicine through the blood-brain barrier in the mouse. Colchicine was administered as a bolus in the jugular vein (1.5 mg kg-1) and its hippocampal extracellular fluid (ECF) and blood kinetics were determined over a 4 h period using two microdialysis probes, one in the dorsal hippocampus, the other in the inferior vena cava. Colchicine rapidly diffused into the hippocampus (maximum concentration in the first dialysate sample) and brain and blood concentrations declined in parallel, suggesting rapid equilibration between these two compartments. However, only 6. 7% of total blood colchicine, 14% of unbound colchicine was present in the hippocampus suggesting that the P-glycoprotein efflux pump limits colchicine uptake by the brain. We also found, using conventional tissue homogenate analysis in parallel, that the concentration of colchicine in the hippocampal ECF was 10 times less than that in the intracellular space and that the hippocampus colchicine concentration was 2.8 times higher than that of the rest of the brain. This study shows that the simultaneous brain and blood microdialysis can be used to measure the passage of colchicine through the blood-brain barrier and to estimate the brain extra- and intracellular distribution of colchicine.

Animals↗

PubMed1987

Extracellular fluid and plasma volumes during water immersion in nephrectomized dogs.

Extracellular fluid volume (ECF, [125I]iothalamate space), blood volume (BV, 51Cr-labeled erythrocyte space), and hematocrit were measured continuously to study the kinetics of fluid movements between intracellular, interstitial, and plasma compartments during water immersion (WI) at 38 degrees C in seven splenectomized and acutely nephrectomized dogs. ECF and plasma volume (PV) increased linearly during WI by 10 +/- 2 ml/kg (4% of initial ECF volume, P less than 0.05) and 12 +/- 2 ml/kg (33% of initial PV, P less than 0.05), respectively, above the control level by 120 min of WI. We estimate that 83% of the fluid entering the intravascular compartment is derived from the intracellular space at 120 min of WI. The results of this study indicate that WI leads to a sustained fluid movement of intracellular fluid toward the intravascular compartment. The increase in interstitial hydrostatic pressure (wick method) by 28.5 mmHg from the control level at 5 min of WI in response to the external water pressure exceeds the increase in mean capillary pressure by 10-11 mmHg relative to the control level. We postulate that this negative hydrostatic pressure gradient across the capillary wall leads to an increase in PV during WI.

Animals↗

PubMed1996

Extracellular iron (II) can protect cells from hydrogen peroxide.

We hypothesized that exposure of cells to H2O2 plus Fe2+ would increase formation of cell-derived lipid peroxides that would inactivate prostaglandin H synthase, resulting in decreased prostaglandin synthesis. Therefore, we treated human endothelial cells with 0-100 microM H2O2 followed immediately by addition of 0-200 microM Fe2+. After oxidant exposure, cells were stimulated with 20 microM arachidonic acid to induce prostaglandin I2 (PGI2) synthesis. Adding 100 microM H2O2 prior to arachidonic acid decreased PGI2 synthesis more than 80%. However, to our surprise, the addition of Fe2+, in increasing amounts, progressively protected PGI2 synthesis against the harmful effects of H2O2. A ratio of one part H2O2 to two parts Fe2+ offered almost complete protection, whereas Fe3+ did not protect PGI2 synthesis from H2O2. We found that 100 microM H2O2 was not cytolytic; however, 250 microM H2O2 was cytolytic; Fe2+ protected against this cytotoxicity. In addition, extracellular Fe2+ prevented the rise in intracellular calcium caused by H2O2 and extracellular Fe2+ preserved intracellular glutathione in H2O2-exposed cells. Electron paramagnetic resonance spin trapping demonstrated that extracellular Fe2+ generated the hydroxyl free radical, HO. outside the cell. We speculate that extracellular Fe2+ protects the intracellular space from H2O2 by initiating the Fenton reaction outside the cell. This reductive cleavage of H2O2 generates HO. in the extracellular space, where much of the HO. will react with noncellular components, thereby protecting the cell interior.

Cells, Cultured↗

PubMed1988

Sequential hypertonic haemodialysis in children.

Sequential hypertonic dialysis (SHD) was studied in two binephrectomized children over a period of 6 weeks. Each dialysis session comprised four periods of 45 min. The concentration of sodium in the dialysate [Na(D)] during the first period was 190 mmol/l and during the second period 140 mmol/l. The sequence was then repeated. The sodium-free water clearance [C(ONa)] was calculated from the measurements of the ultrafiltrate clearance and of the sodium clearance. Despite the short periods of hypertonic dialysis, C(ONa) was positive, suggesting that water was removed from the intracellular compartment as well as from the extracellular fluid. The transfer of fluid from the intracellular space improved circulatory stability during rapid removal of large volumes of fluid by ultrafiltration. SHD was also associated with increased removal of potassium and phosphate. Comparison of clinical parameters before and during SHD showed a tendency towards increased sodium balance and the possibility of raised cardiovascular morbidity. SHD stabilized blood volume during ultrafiltration, encouraging removal of uraemic toxins. SHD with this level of Na(D) is only a study dialysis method.

Child↗

PubMed1990

The extrarenal effects of atrial natriuretic peptide on body fluid distribution.

To study the effects of atrial natriuretic peptide (ANP) on body fluid volume regulation, we estimated the changes in intra- and extravascular fluid volume by measuring hematocrit (Hct), plasma protein concentration and water balance, and the changes in intra- and extracellular fluid volume by the electrical impedance method during intravenous infusion of ANP. We did two studies, as follows: ANP was infused into 18 patients with essential hypertension, 29 with renal parenchymal hypertension and 15 normotensives at 0.025 microgram/kg/min for 40 min. Both hypertensive groups showed greater natriuretic responses to ANP than normotensives. ANP infusion into essential hypertensive patients increased the urinary excretion of water by 125%, Na by 205%, Hct by 4.2% and plasma total protein (TP) by 5.2% (each P less than .001). In 9 patients (1 with renal hypertension and 8 normotensives) who did not show a natriuretic response (-2.1%), the infusion of ANP also significantly increased Hct (3.8%) and plasma TP (3.1%, each P less than .01). The electrical impedance method was applied to 12 subjects to simultaneously detect the intracellular (Ri) and extracellular resistivities (Re), of which reciprocals reflect the fluid volume in the extra- and intracellular spaces, respectively. ANP infusion increased Re in all subjects (3.96 +/- 0.16 [SE] v 4.03 +/- 0.16 omega.m, P less than .05), but decreased Ri in 7. Changes in urinary Na excretion correlated positively with those in both Re (r = 0.62, P less than .05) and Ri (r = 0.75, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

Effect of ovulation on the ionic and water content of rabbit oviduct.

The water content, extracellular space, intracellular water, potassium, sodium and chloride content of oviduct and uterus removed from rabbits in estrus and 24 and 72 h following hCG injection have been determined. Following ovulation, there was an increase in water content of the region of the oviduct corresponding to the ampullary -isthmic junction which, at 24 h, is probably due to increased intracellular water. In the ampullary-isthmic junction, ovulation decreases the potassium content and, at 24 h in the isthmic region of the oviduct, chloride is reduced. The water and ionic content of mucosa and smooth muscle cells has been calculated and mucosa cells have greater intracellular water and chloride and sodium content and less potassium and extracellular space than the smooth muscle cells of the oviduct. The significance of the changes in ionic and water content is discussed.

Animals↗

PubMedDate not supplied

Comparison of [3H]bepridil and [3H]verapamil uptake into rabbit aortic rings.

The efflux and uptake of [3H]Ca antagonists were studied in isolated rings of rabbit aorta. The efflux of [3H]bepridil occurred from two compartments. The faster (T1/2 = 0.6 min) initial compartment presumably represented efflux from the extracellular space. The slower (T1/2 = 25 min) component probably reflected efflux from the intracellular space. The uptake of [3H]bepridil into the cells occurred at an initial rate of 0.001 pmol/s . cm2, and by 80 min, uptake had reached steady state. Increasing the Ca2+ concentration to four times normal caused a marked decrease in the [3H]bepridil uptake, implying a possible competition between Ca2+ and bepridil. However, decreasing the Ca2+ concentration to one-fourth normal caused a slight decrease in [3H]bepridil uptake. [3H]Verapamil was not appreciably taken up by the tissues (less than 10% of [3H]bepridil uptake) unless the cell membranes were disrupted by digitonin treatment. (Lowering the Ca2+ concentration to one-fourth normal slightly increased. [3H]verapamil uptake.) These data suggest that bepridil can cross the sarcolemma (and therefore may exert some internal effect), whereas verapamil is effectively excluded from the cell interior by the cell membrane.

Absorption↗

PubMed1993

Inhibition of hepatic gluconeogenesis by niflumic acid correlates with the concentration of the free form.

Inhibition of hepatic gluconeogenesis by niflumic acid, a non-steroidal antiinflammatory drug, was measured in order to correlate the effect of the drug with the concentration of the free drug. The concentration of free drug was changed in two ways: (a) by changing the albumin concentration at a fixed total (free+bound) niflumic acid concentration; and, (b) by changing the drug concentration at a fixed albumin concentration. The degree of inhibition of gluconeogenesis by niflumic acid depends strictly on the concentration of the free drug, with half-maximal inhibition at 19.25 microM. This result is consistent with binding equilibrium in the extracellular space and with a flow-limited distribution between the extra- and intracellular spaces as proposed by our previous work.

Animals↗

PubMed1980

Potassium deficiency enhances the effect of thyroid hormone on NaK-ATPase in liver and kidney.

In order to examine the possibility that the changes in electrolytes in tissue alter the effect of thyroid hormone on NaK-ATPase, rats were fed either synthetic K-deficient diet or synthetic K-normal diet. K-deficient diet induced a reduction in K content in serum or kidney, while that of the liver remained unchanged. When a daily dose of 2.5 micrograms T3 was administered for 7 days to k-deficient rats, both Mg- and NaK-ATPase of the homogenate of liver and kidney were elevated, while the same dose failed to influence those enzymes in K-normal rats. Furthermore, T3 dose increased the Na content of liver and kidney in K-deficient rats, resulting in a significant decrease in th K/Na ratio in those tissue. Based on the estimation from chloride space, the decrease in K/Na was deemed to have occurred mainly in the intracellular space. As the levels of serum thyroid hormone and liver T3 were not influenced by K-deficiency, the effect of K depletion is likely to be mediated not through the alteration in thyroid hormone kinetics, but through some other mechanism such as the elevation of intracellular Na. The present study demonstrates that K deficiency may sensitize NaK-ATPase to the effect of thyroid hormone.

Adenosine Triphosphatases↗

PubMed2001

Diffusion NMR spectroscopy.

MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.

Animals↗

PubMed1986

Amplification of prostaglandin E2 stimulation of luteinizing hormone-releasing hormone release from median eminence explants: a metal(II)-specific effect of chelated copper.

We have previously demonstrated that extracellular copper amplifies prostaglandin (PG) E2 stimulation of the release of luteinizing hormone-releasing hormone (LH-RH) from explants of the median eminence area (MEA). Two questions were addressed: what is the active form of copper and the metal(II) specificity for copper action? MEA explants were incubated for 5 min in the presence of CuCl2 (ionic) or copper complexed to histidine (CuHis) at a concentration of 200 microM each and then for 15 min in the presence of 10 microM PGE2. It was found that chelated copper but not ionic amplified PGE2 action, and that the magnitude of PGE2 stimulation of LH-RH release was 3-4-fold in copper-treated than untreated tissue. Moreover, PGE2-stimulated release was directly related to the dose of CuHis. To test the metal specificity, MEA explants were incubated for 5 min with one of the following metal(II) complexes: CuHis, NiHis, FeHis, ZnHis, CdHis, MnHis, or BaHis (200 microM each) and then for 15 min with 10 microM PGE2. Controls were incubated with metal(II) complex or PGE2. Of these complexes, only CuHis and to a lesser extent NiHis stimulated LH-RH release. However, CuHis was the only complex that amplified PGE2 stimulation of LH-RH release. Thus, amplification is specific for copper. The finding that chelated copper but not ionic copper amplifies PGE2 is suggestive that the copper-interactive sites on the LH-RH neurons are not exposed to the extracellular space but that they are either embedded in the plasma membrane, facing the intracellular space, or in the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Feedback inhibition of rat amiloride-sensitive epithelial sodium channels expressed in Xenopus laevis oocytes.

1. Regulation of the amiloride-sensitive epithelial sodium channel (ENaC) is essential for the control of body sodium homeostasis. The downregulation of the activity of this Na+ channel that occurs when the intracellular Na+ concentration ([Na+]i) is increased is known as feedback inhibition. Although intracellular Na+ is the trigger for this phenomenon, its cellular and molecular mediators are unknown. 2. We used the 'cut-open oocyte' technique to control the composition of the intracellular milieu of Xenopus oocytes expressing rat ENaCs to enable us to test several factors potentially involved in feedback inhibition. 3. The effects of perfusion of the intracellular space were demonstrated by an electromicrographic study and the time course of the intracellular solution exchange was established by observing the effect of intracellular pH: a decrease from pH 7.4 to 6.5 reduced the amiloride-sensitive current by about 40 % within 2 min. 4. Feedback inhibition was observed in non-perfused oocytes when Na+ entry induced a large increase in [Na+]i. Intracellular perfusion prevented feedback regulation even though the [Na+]i was allowed to increase to values above 50 mM. 5. No effects on the amiloride-sensitive current were observed after changes in the concentration of Na+ (from 1 to 50 mM), Ca2+ (from 10 to 1000 nM) or ATP (from nominally free to 1 or 5 mM) in the intracellular perfusate. 6. We conclude that feedback inhibition requires intracellular factors that can be removed by intracellular perfusion. Although a rise in [Na+]i may be the trigger for the feedback inhibition of the ENaC, this effect is not mediated by a direct effect of Na+, Ca2+ or ATP on the ENaC protein.

Adenosine Triphosphate↗

PubMed1986

Role of calcium in pathogenesis of acute renal failure.

The potential for calcium to play a key role in cell injury has been long suspected. Major sites of calcium action to promote cell injury include the plasma membrane, mitochondria, endoplasmic reticulum, and the cytoskeleton. Major mechanisms of calcium action to promote cell injury include activation of phospholipases, direct and indirect effects on permeability pathways, and effects on contractile and cytoskeletal structure and function. The activation of phospholipases and deterioration of mitochondrial structure and function by calcium appear to be most important in the evolution of cell injury. Tissue calcium levels invariably increase when lethal cell injury develops in a tissue and is due predominantly to mitochondrial accumulation and sequestration. The simultaneous occurrence of cell calcium overload and lethal cell injury, however, only establishes an association between these two events but does not prove causality. Over the past several years, a large amount of data has established that calcium plays a critical modifying role in the pathogenesis of both ischemic and toxic cell injury, but evidence for the thesis that calcium is the "final common pathway" for lethal cell injury is not conclusive. Many studies have emphasized the role of calcium influx from extracellular to intracellular spaces with resulting cellular calcium overload in cell injury. A critical role for intracellular redistribution of calcium pools rather than cellular calcium influx during the important early stages of cell injury may be more important. Modifying alterations in cell calcium redistribution or cellular calcium influx with a variety of agents has been beneficial in ameliorating the degree of cell injury in a number of experimental settings. It is still unclear whether these beneficial effects are due mainly to alterations of calcium-mediated processes that determine the reversibility of injury or are due to alterations in other critical metabolic processes not importantly influenced by calcium.

Acute Kidney Injury↗

PubMed1985

Volume regulation and plasma membrane injury in aerobic, anaerobic, and ischemic myocardium in vitro. Effects of osmotic cell swelling on plasma membrane integrity.

The relationship between cell swelling and plasma membrane disruption has been evaluated in thin myocardial slices incubated in oxygenated or anoxic Krebs-Ringer phosphate media. Electron microscopy and measurements of inulin-diffusible space were used to monitor plasma membrane integrity. Inulin is excluded from the intracellular space of intact cells; therefore, an increase in tissue inulin content is an excellent marker of loss of plasma membrane integrity. Cell volume was increased during exposure of aerobic slices to hypotonic media, but the inulin-diffusible space was not increased and electron micrographs showed no detectable plasma membrane alterations. Likewise, during prolonged anoxic isotonic incubation, no evidence of plasma membrane damage was observed. Incubation in anoxic hypotonic media for 60 minutes resulted in a larger increase in cell volume than under aerobic conditions, but plasma membrane integrity was maintained. Extended anoxic hypotonic incubation (300 minutes) produced no further change in tissue water, but the inulin-diffusible space was increased and electron micrographs revealed breaks in the plasma membranes primarily in association with large subsarcolemmal blebs. Likewise, myocardial slices incubated in isotonic anoxic media for 240 minutes and hypotonic anoxic media for 60 minutes had an increased inulin-diffusible space and the ultrastructural appearance was similar. This ultrastructural appearance is indistinguishable from that observed in myocytes lethally injured by ischemia. Measurements of tissue osmolarity during total ischemia showed that osmotically induced cell swelling could occur in ischemic myocardium prior to the onset of plasma membrane disruption. Our results indicate that cell swelling per se is incapable of rupturing plasma membranes; however, after prolonged periods of energy deficiency, the plasma membrane or its cytoskeletal scaffold become injured, which allows the membrane to rupture if the cell is swollen, as might occur during ischemia or reperfusion.

Aerobiosis↗

PubMed1977

Ultrastructural pattern of acetylcholinesterase distribution in the cerebellar cortex of the quail.

The ultrastructural localization of acetylcholinesterase (AChE) was studied in the cerebellar cortex of the quail by means of histochemical method. The greater amount of AChE was detected at leve of the molecular layer in the intracellular spaces between parallel fibers and between parallel fibers and dendritic terminals. Many neurons showed intracellular localization of enzyme activity: the AChE positive neurons were all Golgi cells, most stellate the basket cells and different aliquots of Purkinje and granule cells. The enzymatic activity was usually localized in the cisternae of endoplasmic reticulum, in the nuclear envelope (but this last localization was not present in Purkinje cells- and sometimes in the Golgi apparatus; reaction granules were usually scarce in the different dendritic branches ramifying in the molecular layer. On the basis of the ultrastructural pattern of AChE distribution, some considerations are developed on the methodological aspects concerning the reliability of histochemical methods, the differences recorded at light and electron microscope level, the problems related to extracellular localization of enzyme, the difficulty of establishing a precise correlation between AChE localization in a cerebellar neuron and its possible cholinergic and/or cholinoceptive nature.

Acetylcholinesterase↗

PubMed2000

Effect of NC100150 injection on the (1)H NMR linewidth of human whole blood ex vivo: dependency on blood oxygen tension.

The linewidth of the (1)H NMR signal (7.05 T) of human whole blood titrated with a superparamagnetic contrast agent (NC100150 injection) was evaluated at different blood oxygen tensions. In deoxygenated blood and low contrast agent concentrations, NC100150 injection caused a decrease in linewidth. After reaching a minimum, the linewidth increased as the concentration of NC100150 injection increased. At the concentration corresponding to the minimum linewidth, the magnetization of the extracellular space containing the NC100150 injection was equal to that of the paramagnetic (deoxygenated hemoglobin) intracellular space. The minimum linewidth is therefore consistent with a complete elimination of the local microscopic susceptibility effect, the major cause of linebroadening. Additionally, phantom studies were performed at 1.5 T, confirming that the contrast enhancement of NC100150 injection in blood is dependent on oxygen tension. The data suggest that NC100150 injection may be useful in differentiating vessels with varying relative oxygen tensions.

Blood↗

PubMed2005

Internodal sodium channels ensure active processes under myelin manifesting in depolarizing afterpotentials.

The current opinion about processes in myelinated axon is that action potential saltatorially propagates between nodes of Ranvier and passively charges internodal axolemma thus causing depolarizing afterpotentials (DAP). Demyelination blocks the conduction that gives additional argument in favor of hypothesis that internode is not able to be activated by the existing internodal sodium channels. The results of our modeling study shows that, when periaxonal space is sufficiently narrow, saltatorial action potential is able to activate internodes. Low density of internodal sodium channels is sufficient to generate active internodal waves that slowly propagate from nodes towards corresponding midinternodes where they collide. The periaxonal width that stops internodal wave propagation (about 400 nm) is significantly larger than the highest value of the physiological range for this parameter (30 nm). Internodal activation is directly manifested as transmembrane internodal potential or as a full-sized action potential in periaxonal space where it can hardly be detected, and only as a small deflection in intracellular space. However, changes in the periaxonal potential cause transmyelin currents that lead to significant DAP. The shape and amplitude of DAP depends on myelin parameters and densities of internodal channels. Several technical parameters affect the results of calculations. Internodal spatial segmentation has to be sufficiently fine (at most 20 microm) for the model to be able to simulate internodal activation. We employ 338 internodal segments as compared with up to 21 used in previous models. Ionic accumulation together with related diffusive and electrical processes alter the calculated DAP amplitude. Inclusion of these processes in calculations demands such increase in the total number of segments that the numerical methods used up to now become unapplicable. To overcome the problem, an iterative implicit approach is proposed. It reduces a matrix of general type in multi-cable models to tridiagonal one and accelerates calculations considerably.

Action Potentials↗

PubMed2006

Transmission electron microscopy and autofluorescence findings in the cornea of diabetic rats treated with aminoguanidine.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) has been implicated in the pathogenesis of diabetic keratopathy. The present study was aimed to understand if aminoguanidine (AG), an AGE inhibitor, was protective against the development of corneal complications in a diabetic rat model. METHODS: Wistar rats were divided into three experimental groups: control, diabetic, and AG-treated diabetic. Diabetes was induced in rats via a single intraperitoneal injection (60 mg/kg) of streptozocin (STZ) and AG was administered in drinking water at a dose of 1 g/L. All animals were sacrificed at the end of 10 weeks and corneas from diabetic and nondiabetic rats were analyzed via transmission electron microscopy (TEM). Corneal autofluorescence measurements were also performed in all experimental groups. RESULTS: Electron microscopic evaluation revealed that aminoguanidine treatment in diabetic rats prevented the formation of intracellular spaces between neighbouring cells in the superficial corneal epithelium. Hyperglycemia-induced degeneration of intracellular organelles and formation of cytoplasmic vacuoles in the corneal stroma was also prevented with the treatment of AG. Corneal autofluorescence detected in the diabetic group (5.98 +/- 2.17 Fi/mg protein) was found to be significantly greater than the control (3.92 +/- 0.56 Fi/mg protein) and the AG-treated diabetic group (4.18 +/- 0.59 Fi/mg protein) (p < 0.05). INTERPRETATION: The presented data provide evidence that AG is preventive against corneal alterations in experimental diabetes.

Animals↗