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At least 415 records · Page 23Linked to original sources
PubMed2003

Pharmacokinetics of L-dopa in plasma and extracellular fluid of striatum in common marmosets.

L-3, 4-Dihydroxyphenylalanine (L-dopa) has been widely used for the treatment of Parkinson's disease (PD), but its pharmacokinetics in the striatum have hardly been investigated, especially in primates. In this study, we examined the concentration of L-dopa in plasma and in the extracellular fluid (ECF) of the striatum in common marmosets using microdialysis and high-performance liquid chromatography (HPLC) with electrochemical detection. With a clinically therapeutic dosage of L-dopa/benserazide (20/5 mg/kg, p.o.), the t(max) of L-dopa was 30 min in plasma and 60-90 min in ECF of striatum. Mean C(max) was 20.3 microM in plasma and 442.9 nM in ECF of striatum, which is about 2.2% of that in plasma. The L-dopa concentration in ECF is much lower than those previously applied during in vivo studies for L-dopa toxicity.

Animals↗
PubMed1976

Sodium chloride restriction and extracellular fluid volume contraction in hyperphosphatiuric vitamin D resistant rickets in the Lowe syndrome.

A patient with a Lowe syndrome was observed from birth. Progressive hyperchloraemic renal tubular acidosis, hypophosphataemia, hyperphosphaturia and generalized hyperaminoaciduria had developed in infancy. Supplementary vitamin D, alkali and a high intake of dietary phosphate were unsuccessful in controlling the severe phosphate diabetes and rickets. Contraction of the extracellular fluid volume by dietary sodium restriction resulted in correction of the acidosis, hypophosphataemia, hyperaminoaciduria, and hyperphosphaturia, and healing of the rickets.

Acidosis, Renal Tubular↗
PubMed1976

Re-evaluation of the role of aldosterone in mechanism of natriuresis induced by extracellular fluid volume expansion.

Acute experiments were performed in thiobarbiturate (Inactin, PROMONTA) anaesthesia in 21 male rats. It was found that the attenuation of the antinatriuretic effect of aldosterone by a spironolactone Aldactone (BOEHRINGER) in a dose of 10 mg per rat in 1 h i.v. enhanced urine (V) and sodium (UNaV) excretion following the extracellular fluid volume expansion (ECFV) with intravenous infusion of saline. Max. V = 81.44 +/- +/- 7.46 mul min-1 was obtained in Aldactone treated rats as compared to 54.95 + 7.24 mul min-1 in controls: UNaV = 9.89 +/- 1.26 muval min-1 vs. 6.17 +/- 0.73 muval min-1, respectively. The urinary Na/K ratio was also significantly higher in the same samples of Aldactone treated rats (6.15 +/- +/- 1.22 vs. 2.68 +/- 0.19). It is concluded that endogenous aldosterone blunts nriuresis induced by the ECFV expansion.

Animals↗
PubMed2001

Concentration of enzymatically active prostate-specific antigen (PSA) in the extracellular fluid of primary human prostate cancers and human prostate cancer xenograft models.

BACKGROUND: Prostate-specific antigen (PSA) targeted prodrugs are under development in our laboratory. Concentrations of total PSA and enzymatically active PSA produced by various human prostate cancer xenograft models have not been well characterized. METHODS: The concentration of PSA secreted into the extracellular fluid (ECF) in normal human prostate tissue, primary prostate cancers obtained directly from patients, and serially passageable human prostate cancer xenografts (PC-82, LNCaP, LAPC-4) were determined using Tandem assays. Percent enzymatically active PSA in the ECF and in conditioned media was also determined using a previously validated assay employing a monoclonal antibody to the PSA catalytic site. In addition, the concentration and activity of PSA within sera from men with and without prostate cancer, as well as from tumor-bearing animals, was likewise assayed. RESULTS: Normal human prostate tissue and primary human prostate cancers have high concentrations of PSA in the ECF (i.e., 1600-2100 nM). The majority of this PSA is enzymatically active (i.e., 80-90%). Human PC-82 prostate cancer xenografts also have high concentrations of PSA in the ECF (624 +/- 360 nM), and the majority of this PSA is also enzymatically active (i.e., 66 +/- 4%). In contrast, much lower concentrations of PSA are found in the ECF from LNCaP (45 +/- 9 nM) and LAPC-4 (7.3 +/- 0.6 nM). Only a small portion of the total PSA isolated from DHT-containing, serum-free, conditioned media from these cell lines is enzymatically active (i.e., approximately 18%). While PSA was detected in all serum samples regardless of the type of host, no enzymatically active PSA was detected in any of these serum samples. CONCLUSIONS: Prostate cancers obtained directly from patients produce and secrete large amounts of PSA, the majority of which is highly enzymatically active. In contrast, while PSA was detected in the sera, none of this PSA was enzymatically active. This is also the case for the human PC-82 prostate cancer xenografts. In contrast, LNCaP and LAPC-4 human prostate cancer xenograft models secrete approximately 70-300-fold less PSA in the ECF than prostate cancers from patients and the majority of this PSA is enzymatically inactive. Also, the serum from these animals had detectable PSA, but none of this PSA was enzymatically active. Thus, these latter two prostate cancer models define the least and the PC-82, the most, optimized xenograft model for screening PSA targeted prodrugs.

Amino Acid Sequence↗
PubMed1976

Plasma renin activity, plasma angiotensin II and extracellular fluid volume in patients after renal transplantation.

1. Patients with cadaveric renal transplants and plasma creatinine less than 177 micronmol/l who had their own kidneys removed were studied. 2. The renin-angiotensin system appeared to behave in a normal fashion in response to alterations in sodium intake and posture. 3. The renin-angiotensin system had no major role in the establishment or maintenance of hypertension. 4. Mean arterial pressure was directly related to expansion of the extracellular fluid volume.

Angiotensin II↗
PubMed1985

Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardial-infarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx. To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6. These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre- and post-glomerular vessels as well.

Adrenergic Fibers↗
PubMed2004

Polycyclic aromatic hydrocarbon biodegradation in extracellular fluids and static batch cultures of selected sub-tropical white rot fungi.

Four sub-tropical white rot fungi, Trametes versicolor, Trametes pocas, Trametes cingulata and isolate DSPM95 were studied alongside the well studied white rot fungus, Phanerochaete chrysosporium, for their ability to remove polycyclic aromatic hydrocarbons (PAHs) from culture media. Both static shallow cultures and extracellular fluids were studied using media contaminated with a defined mixture of the PAHs; fluorene, phenanthrene, anthracene, pyrene and benzo(a)anthracene. With all isolates, the total loss of the parent compound in 31 days was high for fluorene, at +60%, phenanthrene at +40% and anthracene at +42%. Biotransformation of pyrene and benzo(a)anthracene by all the isolates was low, with the highest reduction of pyrene of 15.2% and benzo(a)anthracene of 15.8% being achieved with P. chrysosporium. Disappearance of the more condensed PAHs, pyrene and benzo(a)anthracene, increased in shallow static cultures with the addition of glucose and glucose oxidase as a source of additional H2O2. The addition of Mn2+ and ABTS (2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)) to culture supernatants was associated with higher levels of biotransformation. Comparison of the isolates T. versicolor, T. pocas, T. cingulata and isolate DSPM95 with P. chrysosporium showed that these strains were competitive in the reduction of the PAHs, reducing the PAHs by more or less the same magnitude. Also these sub-tropical isolates did not accumulate a lot of HPLC detectable metabolites as much as P. chrysosporium.

Basidiomycota↗
PubMed1970

On the influence of extracellular fluid volume expansion and of uremia on bicarbonate reabsorption in man.

The patterns of bicarbonate reabsorption during increasing plasma concentrations were studied in subjects with a range of glomerular filtration rates (GFR) from 170 to 2 ml/min. In a group of five subjects with GFR values above 30 ml/min, paired bicarbonate titration studies were performed first under conditions which minimized extracellular fluid (ECF) volume expansion, and second under conditions which were conducive to exaggerated expansion of ECF volume. In patients with GFR values below 30 ml/min, a single protocol was employed. Studies also were performed on two patients with far advanced renal disease who were nephrotic and exhibited a sodium-retaining state. When ECF volume expansion was minimized in the nonuremic subjects, values for bicarbonate reabsorption were well in excess of the usually accepted Tm level and over the range of plasma bicarbonate concentrations employed, no evidence of a Tm phenomenon was observed. A similar pattern emerged in the two nephrotic patients despite the presence of uremia. However, with both exaggerated expansion of ECF volume (GFR greater than 30) and in patients with advanced renal disease in the absence of exaggerated ECF volume expansion a tendency towards saturation kinetics for bicarbonate reabsorption was demonstrable. In comparing the minimized with the exaggerated expansion studies, evidence emerged for a decrease in both bicarbonate reabsorption per unit of GFR and the absolute rate of bicarbonate reabsorption. When ECF volume expansion was exaggerated in uremic patients after stable rates of bicarbonate reabsorption had been achieved, a decrease in reabsorption per unit of GFR and in absolute bicarbonate reabsorption occurred. The possible relationship of the factors controlling sodium excretion to the observed patterns of bicarbonate reabsorption is considered in the text.

Absorption↗
PubMed1977

Amniotic prolactin control over amniotic and fetal extracellular fluid water and electrolytes in the rhesus monkey.

Administration of 1-10 mg ovine pituitary prolactin (oPRL) into the amniotic fluid of 10 rhesus monkeys in the last third of gestation consistently caused a decrease in amniotic fluid volume not seen when saline, vasopressin, or bovine serum albumin were injected into 9 other monkeys. The effects lasted for 24 h. Intraamniotic injection of 10 mg oPRL prevented or reversed a doubling of water and electrolyte content of the fetal extracellular fluid (ECF) volume in the face of hypertonic amniotic fluid. Efflux of these substances from the fetal ECF in the face of hypotonic amniotic fluid was similarly prevented or reversed by intraamniotic prolactin injection. Ovine PRL had no effect on fetal ECF water and electrolytes in the face of isotonic amniotic fluid. Possible sites of these oPRL effects were amnion, placenta, fetal lung and/or fetal gastrointestinal tract.

Amnion↗
PubMed1995

Relationship between morphine analgesia and cortical extracellular fluid levels of morphine and its metabolites in the rat: a microdialysis study.

1. The effect of morphine (10 mg kg-1, s.c.) on the analgesic response measured by the tail-flick method was determined in male Sprague-Dawley rats. The analgesic response to morphine was correlated with the levels of morphine and its metabolites collected by microdialysis from the cortical extracellular fluid (ECF). 2. The analgesic response to morphine lasted for 4 h. The concentration of morphine during a 4 h collection period was significantly higher than the metabolites concentration. The relative concentration of morphine and its metabolites during the 4 h period was 70 and 30% respectively. 3. The analgesic response during the first 2.25 h period accounted for more than 82% of the total analgesia as determined by the area under the time-response curve (AUC). The concentration of morphine and its metabolites during the same period were 78 and 22%, respectively, but they did not differ during the 2.25-4.0 h period (52 and 48%). 4. The half-life for morphine and its metabolites were similar, the maximal achievable concentration Cmax and AUC0-4 h were lower for metabolites but the time to reach maximum concentration was higher for morphine metabolites than for morphine. The ratio of the concentration of metabolites to the concentration of morphine in the cortical ECF increased with time whereas the analgesic response to morphine decreased with time. 5. At several time points following morphine injection even though the levels of morphine were the same, the concentration of metabolites (mainly M3G) differed and thus the ratio [metabolite/morphine]. A plot of [metabolite]/[morphine] vs. analgesia gave a high correlation coefficient. Since M3G has been shown to be antianalgesic and is the only metabolite of morphine in the rat, it is concluded that the levels of this metabolite may regulate the analgesic effect of morphine in the rat.

Analgesia↗
PubMed1992

Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation.

After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗
PubMed1985

Effect of furosemide upon extracellular fluid volume depletion and kidney denervation in rats.

The effect of the diuretic Furosemide (4 mg/kg) is tested on rats housed in metabolic, cages. The excretory function of the kidneys is studied over a 2-hour period after Furosemide administration, according to the following parameters: diuresis, glomerular filtration, excretion and excretory functions of sodium, potassium, chlorine and total osmotically active substances. Reduction of the volume of the extracellular fluid (ECF) is induced by intraperitoneal administration of 0.3 M glucose solution in amount equal to 10 per cent of the body mass. Comparative studies are carried out in animals with intact kidneys (IK) and with bilaterally denervated kidneys (DK). The decreased ECF volume is found to limit strongly the diuretic and saliuretic effect of Furosemide. In the experimental animals with DK, the reduced ECF volume reduced the diuretic and saliuretic effect of Furosemide to a considerably lesser extent. In euvolemic animals Furosemide has potentiated effect in the case of DK. The conclusion reached is that intact kidney innervation is necessary for the Na-retaining function of the kidneys in the case of depleted ECF volume.

Aldosterone↗
PubMedDate not supplied

Response of atrial natriuretic factor to acute extracellular fluid volume in patients with pheochromocytoma.

BACKGROUND: Patients with pheochromocytoma have been reported to show high plasmatic atrial natriuretic factor (ANF) levels. Its source may not be the atrium because blood volume, the most important physiological stimulus for ANF release, is usually reduced in these patients. METHODS: To evaluate ANF secretion functional integrity, we studied three patients with pheochromocytoma before and after surgical removal of the tumor. Extracellular fluid (ECF) volume, plasmatic ANF levels, and plasmatic renin activity (PRA) were measured. ANF was measured before and after an acute saline load of 1.5L in 90 min. RESULTS: Before surgery, ECF volume was normal or reduced, and PRA was normal but decreased after the saline load. By contrast, ANF was elevated and did not change after the saline load. After surgery ANF decreased, ECF volume rose, and the saline load induced a significant increase of plasma ANF and reduction of PRA. ANF was present in significant amounts in tumoral tissue homogenates. CONCLUSIONS: These data suggest that the tumor was the source of ANF in these patients with pheochromocytoma because high levels of ANF, despite reduced or normal ECF volume, as well as unresponsiveness to acute saline infusion, were found before surgery with subsequent normalization after tumor removal.

Adrenal Gland Neoplasms↗
PubMed1982

Brain extracellular fluid pH and blood flow during isocapnic and hypocapnic hypoxia.

Cerebrovascular responses to 30 min of isocapnic hypoxia [arterial O2 partial pressure (PaO2) = 33 +/- 1 Torr; means +/- SE] were examined in eight chloralose-urethan-anesthetized, paralyzed, and artificially ventilated New Zealand White rabbits. Cerebral blood flow (Q) was measured using the radioactive microsphere technique. Vascular resistance (R) was calculated from arterial pressure and Q. Brain extracellular fluid (ECF) pH was measured continuously in the same animals using pH microelectrodes (1- to 2-micrometers tip diameter) placed stereotaxically in the diencephalon. Diencephalon Q increased from 40 +/- 2 to 69 +/- 4 ml . 100 g-1 . min-1 (P less than 0.05) as R decreased (P less than 0.05) after 4-6 min of isocapnic hypoxia. Total brain Q and R changes resembled those of the diencephalon. The ECF pH of the diencephalon increased by 0.016 +/- 0.006 (P less than 0.05) after 1 min of isocapnic hypoxia and remained significantly elevated through the first 20 min of hypoxia. Ten minutes after the return of normoxia Q and R were at control levels, whereas diencephalon ECF pH was 0.043 +/- 0.006 below control (P less than 0.05). Five additional rabbits were prepared as described above then made hypocapnic [arterial CO2 partial pressure (PaCO2) = 21 +/- 0.3 Torr] for 18 min. Diencephalon and total brain Q and R remained at control levels through 12-14 min of hyperventilation, whereas diencephalon ECF pH was elevated by 0.03 +/- 0.006 (P less than 0.05). Hyperventilation was then continued with hypoxic gas to lower PaO2 to 35 +/- 4 Torr for 30 min. Both diencephalon and total brain R decreased (P less than 0.05), with no change in Q after 4-6 min of hypocapnic hypoxia. Diencephalon ECF pH was not significantly different from control throughout the hypocapnic-hypoxic period. We conclude that the early cerebral vasodilation during hypoxia is not mediated by increased brain ECF acidity.

Animals↗
PubMed1992

Expressing glomerular filtration rate in terms of extracellular fluid volume.

Glomerular filtration rate (GFR) is routinely calculated from the second exponential of the bi-exponential plasma clearance of filtration markers such as Cr-51 EDTA and Tc-99m DTPA. By ignoring the first exponential, true GFR is overestimated, an error which increases with increasing GFR. The rate constant, lambda 2, of the second exponential represents the rate at which glomerular filtration 'turns over' the extracellular fluid (ECF) and so closely approximates GFR/ECF volume. Again, the error in the estimation of this ratio increases with increasing GFR, although in this case it underestimates the true ratio. Expressing GFR in terms of ECF volume, rather than in terms of body surface area, offers considerable technical and physiological advantages. The relationship between GFR/ECF volume and lambda 2, over a wide range of renal function, expressed as a second order polynomial, was GFR/ECF volume = -0.093 + 1.06 lambda 2 + 0.009 lambda 2(2) ml.min-1.l-1. The corresponding relationship between 'true' GFR (C1) and approximate GFR (i.e. based only on the second exponential--C2) was C1 = -0.58 + 1.012C2 -0.0011 C2(2) ml.min-1 For any level of renal function, the error in GFR/ECF volume, expressed as lambda 2, is less than the error in GFR expressed as C2. Since GFR may change as a direct result of a change in ECF volume, it is physiologically more relevant, and technically very much easier, to express GFR in terms of ECF volume rather than body surface area.

Adult↗
PubMed1969

On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat.

Bicarbonate reabsorption is classically regarded as a rate-limited process characterized by saturation kinetics. The tubular maximum (Tm), however, varies with glomerular filtration rate. Thus bicarbonate reabsorption, in common with sodium reabsorption, is characterized by glomerulo-tubular balance. The examination of bicarbonate reabsorption is accomplished using the bicarbonate titration technique; however, this method in its traditional form leads to marked expansion of extracellular fluid (ECF) volume. The possibility exists, therefore, that glomerulo-tubular balance for bicarbonate is altered by the volume expansion and thus that the classic pattern of reabsorption may actually reflect inhibited bicarbonate reabsorptive capacity. The present studies were performed in rats to examine this possibility. Bicarbonate titration studies were performed in two groups of animals: (a) those in which ECF volume expansion was minimized; and (b) those in which ECF volume expansion was exaggerated. In the first group, no Tm for bicarbonate was observed either in the majority of individual rats studied or in a group plot for all rats studied despite the fact that plasma bicarbonate concentrations were increased to values in excess of 60 mEq/liter. In the second group, a clear Tm was demonstrated both in individual animals and in group data and there was a lowered threshold for the excretion of bicarbonate. The data thus lend support to the view that the "normal" Tm for bicarbonate may actually represent an inhibited level of bicarbonate reabsorption induced by ECF volume expansion.

Animals↗
PubMed1978

Determinants of high blood pressure in salt-deprived renal hypertensive rats: role of changes in plasma volume, extracellular fluid volume and plasma angiotensin II.

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used. 2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only. 3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups. 4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.

Angiotensin II↗