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Results for “EXTRACELLULAR FLUID”

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PubMed1997

[Extraparathyroid hypercalcemias. Physiopathological and therapeutic aspects].

An increase in plasma calcium concentration is always the consequence of at least one of the following events: an increase in the net calcium input in extracellular fluid, a decrease in glomerular filtration rate, and an increase in the tubular reabsorption of the filtered calcium. In parathyroid hormone-related hypercalcemia, that is typically stable with time, the main determinant is the rise in parathyroid hormone-induced tubular calcium reabsorption. By contrast, in parathyroid hormone-independent hypercalcemia, usually steadily progressive (the main cause being hypercalcemia of cancer), the primary event is almost always a rapid increase in the net calcium input in extracellular fluid. The attendant hypercalcemia is commonly poorly tolerated and induces a renal sodium leak and a decrease in extracellular fluid volume. The latter leads to a fall in glomerular filtration rate and a rise in tubular calcium reabsorption which, in turn, worsen hypercalcemia. Treatment includes a reexpansion of extracellular fluid volume and the inhibition of bone calcium release.

Calcium↗

PubMed1993

Extracellular and cerebrospinal fluids.

The mechanism of formation of extracellular fluid is first described, followed by an explanation of the relation between osmotic force, reflection coefficient and molecular size. The possible mechanism of brain extracellular fluid formation is then proposed in relation to the restriction offered by the blood-brain barrier. The functions and compositions of cerebrospinal fluid (CSF) are then described followed by sections on the process of formation of CSF, the non-electrolytes and proteins in CSF, the drainage mechanisms and protein synthesis by the choroid plexus.

Animals↗

PubMed1980

The clinical physiology of water metabolism. Part III: The water depletion (hyperosmolar) and water excess (hyposmolar) syndromes.

Hyperosmolality occurs when there are defects in the two major homeostatic mechanisms required for water balance-thirst and arginine vasopressin (AVP) release. In this situation hypotonic fluids are lost in substantial quantities causing depletion of both intracellular and extracellular fluid compartments. Patients with essential hypernatremia have defective osmotically stimulated AVP release and thirst but may have intact mechanisms for AVP release following hypovolemia. Hyperosmolality can also be seen in circumstances in which impermeable solutes are present in excessive quantities in extracellular fluid. Under these conditions there is cellular dehydration and the serum sodium may actually be reduced by water drawn out of cells along an osmotic gradient. Hyposmolality and hyponatremia may be seen in a variety of clinical conditions. Salt depletion, states in which edema occurs and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may all produce severe dilution of body fluids resulting in serious neurologic disturbances. The differential diagnosis of these states is greatly facilitated by careful clinical assessment of extracellular fluid volume and by determination of urine sodium concentration. Treatment of the hyposmolar syndromes is contingent on the pathophysiology of the underlying disorder; hyponatremia due to salt depletion is treated with infusions of isotonic saline whereas mild hyponatremia in cirrhosis and ascites is best treated with water restriction. Severe symptomatic hyponatremia due to SIADH is treated with hypertonic saline therapy, sometimes in association with intravenous administration of furosemide. Less severe, chronic cases may be treated with dichlormethyltetracycline which blocks the action of AVP on the collecting duct.

Adenocarcinoma↗

PubMed1983

Earliest irreversible changes during ischemia.

The ability to synthesize new protein was used as a marker of irreversible neuronal injury in experiments with isolated rabbit retinas exposed to various types of ischemic insult. The retinal neurons were able to fully recover their protein synthetic capacity after 20 min of complete ischemic anoxia, but not after 30 min. There was better toleration to either isolated substrate deprivation or complete anoxia than to both together. Increasing extracellular Mg2+ prolonged toleration to complete ischemic-anoxia. Removing Ca2+ completely from the extracellular fluid exacerbated injury. Moreover, increasing extracellular volume improved toleration to the combined insult. This experiment suggests that injured neurons may elaborate cytotoxic compounds into the extracellular fluid. This suggestion was confirmed by further experiments demonstrating exacerbation of injury following minimum insults when the retina was incubated with other already extensively damaged tissue.

Animals↗

PubMed2005

Microdialysis studies of extracellular reactive oxygen species in skeletal muscle: factors influencing the reduction of cytochrome c and hydroxylation of salicylate.

Identification and quantification of specific reactive oxygen species (ROS) is essential to allow greater understanding into the role that ROS play in tissues and extracellular fluids. Previous studies have examined the reduction of cytochrome c and the hydroxylation of salicylate to detect superoxide and hydroxyl activity, respectively, although the specificity of these assays has been the subject of debate. This study aimed to identify the factors influencing hydroxylation of salicylate and reduction of cytochrome c in microdialysates from skeletal muscle extracellular fluid. Mice were anesthetized and treated with either polyethylene glycol-tagged superoxide dismutase (PEG-SOD), desferrioxamine mesylate (desferal) or N(G)-nitro-l-arginine methyl ester (l-NAME). A further cohort of untreated mice was also studied. Microdialysis probes were placed into the gastrocnemius muscle and perfused with salicylate or cytochrome c prior to, during, and after a period of demanding electrically stimulated contractions. Microdialysates were analysed for the reduction of cytochrome c and hydroxylation of salicylate. Contractile activity was found to increase both the reduction of cytochrome c and the hydroxylation of salicylate in the microdialysates. The reduction of cytochrome c was greater in mice treated with l-NAME compared with control untreated mice and was attenuated in mice treated with PEG-SOD. The hydroxylation of salicylate was attenuated in mice treated with desferal while there was no effect of l-NAME compared with untreated mice. Data support the hypothesis that superoxide and hydroxyl radical activity are the major contributors to the reduction of cytochrome c and hydroxylation of salicylate respectively in microdialysates from skeletal muscle extracellular fluid and indicate that these ROS are increased by contractile activity in skeletal muscle extracellular fluid.

Animals↗

PubMed1997

Effect of alcohol coadministration on the plasma and brain concentrations of cocaine in rats.

We investigated the effect of intravenous alcohol coadministration on the pharmacokinetics of cocaine in awake, freely moving rats using the microdialysis technique. Alcohol coadministration resulted in faster rate of cocaine absorption after intraperitoneal administration leading to higher cocaine plasma concentration. The higher plasma cocaine concentration resulted in a proportional increase in the cocaine brain extracellular fluid concentration. However, cocaine brain extracellular fluid/plasma distribution ratio, determined from the ratio of the corresponding cocaine area under the concentration-time curves, was not affected by alcohol coadministration. Cocaethylene was detected only after administration of cocaine + alcohol. The brain extracellular fluid/plasma distribution ratio of cocaethylene was similar to that of cocaine. The higher cocaine concentrations in plasma and brain extracellular fluid, in addition to the formation of the pharmacologically active metabolite cocaethylene are, at least partially, responsible for the increased cocaine effects produced after administration of this drug combination.

Animals↗

PubMed1990

Video enhanced imaging of the fluorescent Na+ probe SBFI indicates that colonic crypts absorb fluid by generating a hypertonic interstitial fluid.

Extracellular accumulation of Na+ detected by video-enhanced microscopic imaging of the impermeant fluorescent probe SBFI confirms the view that colonic crypts produce a hypertonic ascorbate ca 1000 mOsm.kg-1, thereby generating a large osmotic pressure across the crypt wall. This creates a high fluid tension within the crypt lumen, sufficient to dehydrate faeces. When bathed in Tyrode the SBFI.Na+ fluorescence indicates a [Na+] ca 750 mM within the interstitial space of metabolizing rat descending colon. There is no evidence of interstitial Na+ accumulation in octanol (2 mM) or in rabbit colon incubated with 1.0 mM ouabain and no evidence of Na+ secretion via the crypt lumen during absorption.

Animals↗

PubMed2000

Transport of circulating IGF-I and LR3IGF-I from blood to extracellular wound fluid sites in rats.

Significant levels of IGF-I are found in wound fluid. The contribution that systemic IGF-I makes to the total IGF-I pool in wounds and the influence of IGF binding proteins (IGFBPs) on the delivery of systemic IGF-I to these wound sites has not been established. In the present series of experiments, we have shown that IGF-I flux across a model endothelial cell barrier is decreased in the presence of IGFBPs, whereas flux of Long R(3)IGF-I (LR(3)IGF-I, an IGF-I analogue with low affinity for IGFBPs) is unaffected. On the basis of these findings, the transport of IGF-I and LR(3)IGF-I from blood to extracellular wound fluid was assessed. Wound chambers were implanted subcutaneously in the backs of adult male rats and left in place for 14 days. A single i.v. bolus of either (125)I-IGF-I or (125)I-LR(3)IGF-I (10x10(6) c.p.m.) was administered via a jugular catheter and wound fluid and plasma samples taken at sequential time points between 5 and 240 min. (125)I-LR(3)IGF-I was removed from the circulation more rapidly than (125)I-IGF-I in both sham control and chamber implanted rats. Although implantation of the chambers did not alter the pharmacokinetic parameters of (125)I-IGF-I, significant increases in the steady state volume of distribution, clearance rate and half-life were recorded for (125)I-LR(3)IGF-I. In addition, significantly more intact (125)I-LR(3)IGF-I was recovered in wound fluid than (125)I-IGF-I at each time point, although only 0.08% of administered (125)I-LR(3)IGF-I was recovered per ml of wound fluid at 240 min. Compared with plasma, a greater proportion of wound fluid IGF-I radioactivity had distributed to the lower molecular weight IGFBPs or existed as free peptide. However, a small amount of wound fluid (125)I-IGF-I was detected in the 150 kDa region 30 min after injection. A greater proportion of (125)I-LR(3)IGF-I was associated with the lower molecular weight IGFBPs or existed as free peptide in both wound fluid and plasma. These data point to the importance of IGFBPs in determining the pharmacokinetic parameters of IGF-I in an extracellular fluid-expanded state. They also suggest only a minor role for endocrine IGF-I in surface wound repair.

Analysis of Variance↗

PubMed1995

Arachidonate and other fatty acids mobilize Ca2+ ions and stimulate beta-glucuronidase release in a Ca(2+)-dependent fashion from undifferentiated HL-60 cells.

Arachidonate (1-300 microM) mobilized Ca2+ ions from an intracellular store and stimulated the entry of Ca2+ ions from the extracellular fluid in undifferentiated HL-60 cells that had been loaded with Fura-2. The integrated response was biphasic in form: arachidonate liberated Ca2+ ions from the intracellular store first, resulting in a transient increase in cytosolic free Ca2+ concentration ([Ca2+]i). Ca2+ entry from the extracellular fluid was not evident for a further 1-2 min. At baseline, [Ca2+]i was 48.1 +/- 14.0 nM (SEM, n = 5). Upon addition of arachidonate (100 microM), [Ca2+]i rose to a transient peak level of 217 +/- 38.6 nM (SEM, n = 5) and a later plateau level of 427 +/- 118 nM (SEM, n = 5). Removal of added Ca2+ ions from the extracellular fluid in the presence of EGTA (1.0 mM) had no effect on the initial transient response but abolished the second phase of the response. In HL-60 cells that had been loaded with BAPTA/AM, the initial transient phase of the response was abolished but the elevation in [Ca2+]i due to Ca2+ entry from the extracellular fluid was unaffected. Undifferentiated HL-60 cells also responded to arachidonate (100 microM) with an increase in the release of the lysosomal enzyme beta-glucuronidase. Arachidonate-induced beta-glucuronidase release from BAPTA-loaded cells or in control cells exposed to Ca(2+)-free solutions was inhibited by about 50%. In BAPTA-loaded cells that were incubated with Ca(2+)-free solutions, arachidonate-induced beta-glucuronidase release was inhibited by about 90%. Leukotriene B4 failed to elevate [Ca2+]i in the concentration range 0.01-1 microM and failed to activate beta-glucuronidase release in concentrations up to 10 microM. Furthermore, the cyclo-oxygenase/lipoxygenase inhibitor ETYA (100 microM) was without effect on secretion. Consistent with this finding, we found that a large number of unsaturated fatty acids could reproduce the effect of arachidonate on [Ca2+]i and beta-glucuronidase release. Fatty acids belonging to the omega-3, omega-6 and omega-7 unsaturated fatty acid families were effective in elevating [Ca2+]i and stimulating beta-glucuronidase release. However, three unsaturated fatty acids, all belonging to the omega-9 fatty acid family, were ineffective.

Arachidonic Acid↗

PubMed1984

Extra- and intracellular amino acids in the hippocampus during development of hepatic encephalopathy.

Fulminant hepatic failure was induced in rabbits by intravenous administration of galactosamine hydrochloride. The animals were sacrificed after 45 h and the hippocampus analyzed for free amino acids. In addition, free amino acids were measured in plasma and in the extracellular fluid of the hippocampus 20, 30 and 45 h after galactosamine injection. The extracellular fluid compartment was analyzed by slow perfusion of a thin dialysis tube which was implanted in the hippocampus one day prior to galactosamine administration. The amino acid concentration in the extracellular fluid agreed fairly well with that of the cerebrospinal fluid in the control situation. During development of hepatic failure, the plasma concentration of all amino acids increased. The changes in extracellular amino acids were smaller, except for phosphoethanolamine and glutamate. The concentration ratio intra/extracellular amino acids decreased in the hippocampus for amino acids with a normally high concentration gradient.

Amino Acids↗

PubMed1981

Intracellular and exchangeable potassium in cirrhosis. Evidence against the occurrence of potassium depletion in cirrhosis with ascites.

The intracellular potassium content of leukocytes, the extracellular fluid volume (82Br space), and exchangeable potassium were determined in 28 patients with cirrhosis of the liver (18 with ascites) and in 15 hospitalized controls. No intracellular potassium depletion could be identified in these patients. Leukocyte potassium was similar in cirrhotic patients with and without ascites (355.9 +/- 25.3 and 348.1 +/- 31.9 mEq/kg of dry solids, respectively) and in hospitalized controls (359.7 +/- 27.4) (mean +/- SD). The extracellular fluid volume was similar in controls and cirrhotics without ascites, but markedly increased in cirrhotics with ascites. The exchangeable potassium (mEq/kg of body weight) was similar in nonascitic cirrhotics and in hospitalized controls, but significantly lower in patients with cirrhosis and ascites. However, when the estimated weight of the extracellular fluid volume was substrated from the total body weight, thus obviating the influence of the increased extracellular fluid volume of ascitic patients in the body weight, the exchangeable potassium (mEq/kg of "corrected" body weight) was similar in cirrhosis with ascites (52.9 +/- 6.7 mEq/kg), nonascitic cirrhotics (55.8 +/- 6.1 mEq/kg) and hospitalized controls (55.0 +/- 8.3 mEq/kg), and a significant correlation was obtained between the exchangeable potassium and the leukocyte potassium content. In five patients, the measurements were repeated after relieving ascites with diuretics. No change was observed in the leukocyte potassium, but exchangeable potassium (mEq/kg of body weight) increased, reaching values not significantly different from controls or nonascitic cirrhotics. The exchangeable potassium (mEq/kg of "correct" body weight) did not change. Our results strongly suggest that potassium depletion was not present in the series of cirrhotic patients studied.

Aged↗

PubMed2004

Cefoselis, a beta-lactam antibiotic, easily penetrates the blood-brain barrier and causes seizure independently by glutamate release.

Cefoselis is a widely used beta-lactam antibiotic, but occasionally induces seizures and convulsion in elder and renal failure patients. However, beta-lactams are known not to pass through the blood-brain barrier (BBB). In this study, we examined the BBB penetration of cefoselis in normal and renal failure rats by means of brain microdialysis. Cefoselis was dose-dependently appeared in brain extracellular fluid in proportion to its blood level. The elimination constant from brain extracellular fluid (apparent) was slightly lower than that from blood. These results indicated that cefoselis might penetrate the BBB or be discharged by a certain transport system. In contrast to the result of cefoselis, cefazolin, a leading drug of cephalosporins, could not be detected in the brain extracellular fluid after an intravenous injection. In renal dysfunction rats, the elimination half-lives of cefoselis from both blood and brain were extensively prolonged. This would be one of responsible factors inducing seizures seen in patients. However, the additional factor, such as decrease in brain function related to aging, would be involved in seizures in patient received cefoselis, because an extremely high dose was required to induce seizures even in renal failure rats. A local administration of cefoselis into the hippocampus through the microdialysis probe caused a striking elevation of extracellular glutamate, with a minimum increase in gamma-aminobutyric acid (GABA). However, a systematic cefoselis administration via the tail vein did not elevate extracellular glutamate and GABA concentrations in the hippocampus of renal failure rats that exhibited marked seizures. These results suggested that not the stimulation of glutamate release, but the blockade of GABA receptors might be responsible for the seizure induced by cefoselis.

Animals↗

PubMed1955

Peptidase distribution in lymphatic tissue.

The lymphatic tissue of the rabbit contains a labile peptidase as measured by the hydrolysis of alanylglycine. Some characteristics of the enzyme were determined. This enzyme increases in amount when the numbers of macrophages in the tissue are increased and it is also present in the extracellular fluid in high concentration. The extracellular fluid value for this activity is calculated to be about 8 times the value for serum. Based on a correlation between the types of cells present and the amount of peptidase found in the tissue the following relative activities are assigned to the tissue components per unit volume: lymphocytes 1.0, tissue fluid 11.0, serum 1.4, phagocytes (macrophages) 30.0, reticular cells 12.0. The amount of chloride space varied from 35 to 55 per cent. The relative amounts of acid phosphatase per unit volume in the same elements were calculated to be: lymphocytes 1.0, tissue fluid 0, phagocytes 20.0, and reticular cells 4.0. Analysis of the distribution of peptidase was facilitated by simultaneous determination of acid phosphatase whose primary localization in one cell type was known. The over-all contribution of lymphocytes to the labile peptidase content of lymphatic tissue is relatively minor and was not found to exceed 5 per cent of the average value for the entire nodular tissue. In the absence of large numbers of macrophages the intercellular fluid of the nodule accounts for half or more of the peptidase content of the nodules.

Acid Phosphatase↗

PubMed2005

Role of muscle in regulating extracellular [K+].

There is a positive association between diets rich in potassium, control of blood pressure, and prevention of stroke. Extracellular [K+] is regulated closely to maintain normal membrane excitability by the concerted regulatory responses of muscle and kidney. Although kidney is responsible for ultimately matching K+ output to K+ intake each day, muscle contains more than 90% of the body's K+ and can buffer changes in extracellular fluid [K+] by either acutely taking up extracellular fluid K+ or releasing intracellular fluid K+ from muscle. It long has been assumed that the changes in muscle K+ transport are a function of sodium pump (Na,K-adenosine triphosphatase [Na, K-ATPasel]) abundance, especially that of the alpha2 isoform, which predominates in skeletal muscle. To test the physiologic significance of changes in muscle Na,K-ATPase expression, we developed the K+ clamp, which measures insulin-stimulated cellular K+ uptake in vivo in the conscious rat. By using the K+ clamp we discovered that significant insulin resistance to cell K+ uptake occurs as follows: (1) early in K+ deprivation before a decrease in muscle sodium pump pool size, and (2) during glucocorticoid treatment, which increases muscle Na,K-ATPase alpha2 levels greater than 50%. We also discovered that adaptation of renal and extrarenal K+ handling to altered K+ balance often occurs without changes in plasma [K+], supporting a feedforward mechanism involving K+ sensing in the splanchnic bed and adjustment of K+ handling. These findings establish the advantage of combining molecular analyses of Na,K-ATPase expression and activity with systems analyses of cellular K+ uptake and excretion in vivo to reveal regulatory mechanisms operating to control K+ homeostasis.

Animals↗

PubMed1977

Hypertriglyceridemia in Ehrlich ascites carcinomatous mice: tumor and mouse strain differences.

Ehrlich ascites carcinoma growth in mice induces hypertriglyceridemia. The degree of hypertriglyceridemia found in one laboratory (Spector's) was much greater than we observed in our laboratory. Moreover, major differences were reported with respect to fasting (no effect on tumor extracellular fluid triglyceride levels in Spector's tumor-bearing mice; marked decrease in ours). We have obtained tumorous CBA mice from Spector's laboratory and have studied them simultaneously with our Swiss-Webster mice. Triglyceride levels of the above two groups and from two controlled crossover groups, included to evaluate the influence of mouse and tumor strains on hypertriglyceridemia, were determined. The CBA mice had intense hypertriglyceridemia and high triglyceride levels in tumor extracellular fluid regardless of the subline source of ascites tumor. On the other hand, only mild hyperlipidemia was induced with both strains of tumor in Swiss-Webster mice. Thus, the variations in plasma and tumor extracellular fluid triglyceride levels probably arise from the mouse strains and not from variations in the tumor subline. Fasting caused a decrease in both plasma and tumor extracellular fluid triglyceride concentrations in CBA, as well as in Swiss-Webster mice. A mouse strain difference was also evident from a significant decrease in wet weights of adipose tissues like epididymal fat, inguinal fat, and intermuscular fat with tumor growth in the CBA strain which was not observed in the Swiss-Webster strain at the corresponding stage of tumor growth. Study of these strain diffeences may lead to an understanding of factors that regulate hyperlipidemia.

Animals↗

PubMed1982

Stimulus-secretion coupling of amino acid-induced insulin release VII. The B-cell memory for L-glutamine.

In the absence of another exogenous nutrient, L-glutamine does not stimulate insulin release from rat pancreatic islets or isolated perfused pancreases. L-glutamine, however, augments insulin release evoked by L-leucine. These two amino acids could interact by providing both the substrate (L-glutamate) and an activator (L-leucine) for the reaction catalyzed by glutamate dehydrogenase. Under suitable experimental conditions, as little as 0.5 mM L-glutamine is sufficient to enhance leucine-stimulated insulin release. When the pancreases or islets are first exposed to L-glutamine and then stimulated with L-leucine, the rate of secretion is much higher than that evoked by L-leucine in tissue not first exposed to L-glutamine. The memory of a prior exposure to L-glutamine persists for at least 25 min after removal of the latter amino acid from the extracellular fluid. This memory phenomenon is not dependent on the presence of Ca2+ in the extracellular fluid during the first exposure to L-glutamine, but is suppressed when such a prior exposure is performed in the absence of extracellular K+. The memory phenomenon could be due, in part at least, to inhibition by L-glutamine of K+ conductance in the B-cell plasma membrane. Moreover, the amount of L-glutamate which accumulates in islets exposed to L-glutamine is sufficient to maintain, for a much longer period than with other nutrient secretagogues, a sustained increase in catabolic fluxes after removal of the amino acid from the extracellular fluid.

Animals↗

PubMed1975

Elemental balances during intravenous hyperalimentation of underweight adult subjects.

Intravenous hyperalimentation was done in 11 underweight adults whose body weight (body wt) was less than 85 percent of ideal. For the first 6 days, "complete formula" was infused furnishing per kilogram ideal body wt per day: 15 g glucose, 0.40 g N, 0.018 g P, 2.4 meq K, 3.0 meq Na, 2.3 meq C1, 0.5 meq Mg, 0.45 meq Ca, and 50 ml H20. Patients gained weight at an average rate of 9.0 g/kg ideal body wt/day and showed average balances/kilogram ideal body wt/day as follows: plus 0.14 g N; plus 0.012 g P; plus 0.43 meq K; plus 0.49 meq Na; plus 0.37 meq Cl; and plus 0.085 meq Ca. Application of standard equations to the elemental balances indicated weight gain consisted of 35-50 percent protoplasm, 35-50 percent extracellular fluid, 5-25 percent adipose tissus, and less than 1 percent bone. Withdrawas of N, P, Na, or K impaired or abolished retention of other elements. Removal of N halted retention P, K, Na and C1; withdrawal of K stopped retention of N and P; and removal of Na or P interrupted retention of all other elements. Weight gain continued at a rate of 1.4-3.1 g/kg ideal body wt/day despite zero or negative elemental balances of N, K, P, and sometimes Na and C1. Calculations showed that weight gain during infusion of fluids lacking N, P, K, or Na consisted largely of adipose tissue, with little or no contribution by protoplasm or extracellular fluid. Data show that repletion of protoplasm and extracellular fluid of wasted adults by intravenous hyperalimentation is retarded or abolished if N, P, Na, or K is lacking. Repletion of bone mineral does not occur in absence of Na or P but proceeds in absence of N, P, K, or Na. Thus, quality of weight gained by underfed adult patients during hyperalimentation depends on elemental composition of the infusate.

Adolescent↗

PubMed2003

Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer.

Angiogenesis is essential for tumor growth and metastasis and an important prognostic factor in breast cancer. VEGF, a key factor for angiogenesis, has been correlated with tumor vessel density in breast cancer. Estrogen, another crucial factor in breast cancer, stimulates VEGF; and an ERE in the VEGF gene has been defined. VEGF is bioactive in the extracellular fluid, where it becomes available to endothelial cells. Whether E(2) affects VEGF levels in the extracellular fluid is not known. We show, using intratumoral microdialysis in vivo, that E(2) treatment increased tumor extracellular levels of VEGF in an estrogen-dependent breast cancer model. Moreover, extracellular levels of VEGF in the tumor showed a strong correlation with total tumor VEGF, contrary to plasma levels of VEGF. Ninety-three percent of measured VEGF in the extracellular fluid in the tumor was tumor-derived, while only 45% of VEGF in circulating plasma originated from the tumor. We conclude that E(2) increases extracellular VEGF and that microdialysis is a sensitive method for measurement of local VEGF production in vivo. Our results have potential application to the assessment of tumor characteristics in vivo in human tumors for individualized cancer therapy.

Animals↗