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PubMed1995

Predicting the efficacy of antimicrobial agents in respiratory infections--is tissue concentration a valid measure?

Despite methodological and interpretive problems associated with studies of antibiotic concentrations in tissues, it is important to confirm the presence of a drug in significant concentrations in tissues and fluids at a particular site. For antibiotics used in the treatment of community-acquired respiratory infections, tissue distribution at sites of potential infection in the respiratory tree has been related to clinical outcome. Measurement of antibiotic concentrations achieved in lung parenchyma epithelial lining fluid, bronchial mucosa or bronchial secretions has indicated significant levels for beta-lactams and macrolides. Many respiratory infections are caused by obligate or facultative intracellular pathogens, which may be eradicated as a result of intracellular penetration and accumulation of macrolides, as shown in several models of phagocytic cells, and of intracellular antibacterial activities. For bacterial infections located in extracellular pulmonary sites, a knowledge of achievable concentrations of beta-lactam and of macrolides should be of value. For bacteria multiplying in alveolar macrophages the high concentrations of the new macrolides that can be achieved in extravascular and intracellular fluids should have clinical relevance, as shown in this review. Moreover with newer macrolides one may expect a better patient compliance due to prolonged persistence of drug in tissues and cells which results in shorter duration of treatment and once-daily dose administration. Finally, for some sites of infection and particularly in the human respiratory tree, there is a clear relationship between local concentrations and clinical efficacy.

Animals↗
PubMed1980

Total body electrolyte composition and distribution of body water in uremia.

Total body sodium and chloride were measured by neutron activation analysis, and total body potassium was measured by whole body counting in ten male patients with endstage renal disease requiring chronic maintenance hemodialysis. The extracellular fluid volume was estimated from the simultaneously measured volume of distribution of bromine 77 and sodium 24. Total body water was estimated from the volume of distribution of triated water. Total body sodium and chloride were significantly increased above normal measured values, but total body potassium was not significantly different from normal. The increase in total body sodium could be attributed to an increase in exchangeable sodium because no significant change in the nonexchangeable portion of total body sodium could be detected. Extracellular fluid volume, estimated fro three different techniques (total body chloride, sodium 24, and bromine 77), and total body water were increased significantly above normal values. Extracellular fluid volume was correlated with exchangeable sodium, and total body water was closely correlated with total cation content (exchangeable sodium and total body potassium). The calculated intracellular fluid volume was decreased and was closely correlated with total body potassium. Despite adequate control of uremia by chronic maintenance hemodijalysis, body electrolyte composition and the distribution of body water remain significantly different from normal.

Adult↗
PubMed1989

Managing hypernatremia in fluid deficient elderly.

The institutionalized elderly are at risk for developing fluid volume depletion with progression to hypernatremia. This is particularly common in patients transferred to an acute care setting from a nursing home. A marked reduction in intracellular fluid and the increase in body fat associated with normal aging predispose the elderly to water loss with very little environmental prompting. Conditions contributing to the development of fluid volume deficit include febrile illness, utilization of enteral supplements, gastrointestinal bleeding, use of loop diuretics, renal failure, prolonged vomiting, diarrhea, diabetes, and disability induced fluid restriction. This can lead to apathy and confusion, which are often incorrectly attributed to dementia. The utilization of Roy's Adaptation Model to this problem focuses on the regulator subsystem and the physiologic mode.

Aged↗
PubMedDate not supplied

Relationship of demographic, dietary, and clinical factors to the hydration status of patients on peritoneal dialysis.

OBJECTIVES: To establish which clinical factors are associated with an increased proportion of extracellular fluid (ECF) in peritoneal dialysis (PD) patients. DESIGN: A single-center, cross-sectional analysis of 68 stable PD patients. METHOD: Bioelectrical impedance measurements (RJL, single frequency; RJL Systems, Clinton, Michigan, USA) of resistance and reactance were used to determine the proportion of ECF comprising total body water (TBW) in 68 stable PD patients attending for routine clearance and membrane studies. All patients underwent detailed dietetic, adequacy, and membrane function tests. Blood pressure and antihypertensive requirements were also documented. RESULTS: Significant gender differences in body composition were observed, such that women had lower absolute TBW and fat-free mass per kilogram body weight, but proportionately more ECF for a given TBW, mean ECF:TBW 0.5 +/- 0.03 versus 0.44 +/- 0.05, p < 0.005. In view of this, patients were split into two groups, defined as "over-" or "normally" hydrated, either by using the single discriminator (median ECF:TBW = 0.47) for the whole population, which resulted in groups distorted by gender, or by using different discriminators according to gender (women: 0.49, men 0.45). In both analyses, overhydrated patients were older, had significantly lower plasma albumin, less total fluid removal per kilogram body weight, and higher peritoneal solute transport. When split by a single discriminator, the overhydrated patients had lower sodium removal and significantly less intracellular fluid volume due to an excess of women in this group who also had less residual function and had been on dialysis longer. Using gender-specific discrimination, overhydrated patients were heavier due to expansion of the ECF volume: 20 +/- 4.1 L versus 16 +/- 3.3 L, p < 0.001. Stepwise multivariate analysis found age (p = 0.001), albumin (p = 0.009), and fluid losses per kilogram body weight (p = 0.025) to be independent predictors of gender-adjusted hydration status. Sodium intake did not vary according to hydration status. CONCLUSION: Gender influences the assessment of hydration status of PD patients when employing bioimpedance, such that women tend to have more ECF. Taking this into account, age, albumin, and achieved fluid removal appear to be independently associated with hydration status, whereas peritoneal solute transport is not. Advice on dietary sodium should take account of hydration status and achievable losses.

Adult↗
PubMed2005

Disruption of brain white matter microstructure by excessive intracellular and extracellular fluid in alcoholism: evidence from diffusion tensor imaging.

Magnetic resonance diffusion tensor imaging (DTI) has revealed the disruption of brain white matter microstructure in normal aging and alcoholism undetectable with conventional structural MR imaging. The metrics of DTI can be useful in establishing the nature of the observed microstructural aberrations. Abnormally low fractional anisotropy (FA), a measure of diffusion orientation and coherence, may result from increased intracellular or extracellular fluid, which would be reflected in complementary high apparent diffusion coefficients (bulk mean diffusivity) and low FA, or from disorganization of fiber structure, which would be reflected in low FA but with a lack of the inverse FA and diffusivity relationship. To test these competing possibilities, we examined 15 alcoholic men and 31 control men with DTI to quantify diffusivity in the genu and splenium of the corpus callosum and centrum semiovale. In addition to the previously observed FA deficits in all the three brain regions, the alcoholics had abnormally high white matter diffusivity values in the genu and centrum. Further, inverse correlations between FA and diffusivity were significant in the genu (r=-0.52, p<0.05) and centrum (r=-0.92, p=0.0001). Multiple regression analyses examining diffusivity and age as predictors of FA identified diffusivity as a significant unique contributor to FA in both regions. These results suggest that decreased orientational coherence of brain white matter in alcoholism is attributable, at least in part, to the accumulation of intracellular and extracellular fluid in excess of that occurring in aging, and that the differential influence of these fluid compartments can vary across brain regions.

Adult↗
PubMed1976

Restitution of blood volume after hemorrhage: role of the adrenal cortex.

Splenectomized and adrenalectomized-splenectomized dogs, anesthetized with pentobarbital, were bled so that the role of cortisol in restitution of blood volume could be examined. Intact dogs and adrenalectomized dogs infused with cortisol at a high rate (17 mug/min) showed restoration of blood volume and plasma protein at 24 h, preceded by an early increase in plasma osmolality. Adrenalectomized dogs infused with cortisol at basal rates (2 mug/min) showed no increase in plasma osmolality and no restoration of blood volume or plasma protein at 24 h unless extracellular fluid volume was expanded by exogenous fluid. It is concluded that hemorrhage leads to an increase in extracellular osmolality mediated in part by increased cortisol concentrations. As a consequence, there is a shift of intracellular fluid to the interstitium. The resulting increase in interstitial pressure accelerates lymphatic movement of interstitial protein to the vascular system. This results in a reequilibration of extracellular fluid toward the plasma, thus completing the restitution of blood volume. The osmotically active agents mobilized by cortisol do not appear to be glucose, sodium, or potassium.

Adrenal Cortex↗
PubMed1986

Characteristics of lysine uptake by isolated renal cortical tubule fragments from mature and immature dogs.

The uptake of L-lysine was examined in isolated renal cortical tubule fragments from adult and 1-week-old dogs. Lysine uptake by adult tubules was initially more rapid than that by the immature tubules. This uptake by mature tubules reached a steady state after 30 min of incubation, while the newborn tubules still had not reached a steady state by 90 min of incubation. Because a steady state of lysine uptake was not attained with the immature tubules, their uptake of lysine exceeded that of the adult after 60 min of incubation. Kinetic studies revealed that lysine was taken up by one saturable transport system with a Km of 0.56 mM and Vmax of 6.18 mmol/liter intercellular fluid per 5 min in the adult and one saturable transport system in the 1-week-old with a Km of 0.38 mM and Vmax of 3.66 mmol/l intracellular fluid per 5 min. Lysine also entered the renal tubule cells in both age groups via a diffusional pathway with a kd of 0.35 min-1 in the adult and 0.30 min-1 in the newborn. Cystine competitively inhibited lysine uptake by adult dog tubules with a Ki of 0.61 mM. The other dibasic amino acids, ornithine and arginine, also inhibited lysine uptake in both the adult and the newborn.

Age Factors↗
PubMed1985

Cerebrospinal fluid sodium concentration and salt appetite.

Infusion into a lateral brain ventricle (IVT) of different hypertonic (0.7 M) saccharide solutions decreased [Na+] of cerebrospinal fluid (CSF). Increased Na appetite of moderately Na-deplete sheep was observed during infusion of mannitol, L-glucose or L-fucose, while no change was observed during infusion of D-glucose, D-fucose, D-mannose, 2-deoxy-D-glucose, 3-O-methyl-glucose or fructose. In other experiments, increased Na appetite was observed during infusion of 2.3 mM phlorizin (a relatively specific blocker of Na-coupled glucose transport into cells) or 2.3 mM phlorizin plus 0.7 M D-glucose. In addition, phlorizin eliminated the characteristic decrease in Na appetite but did not affect the increase in water intake caused by IVT infusion of hypertonic NaCl which increased [Na+] of CSF. The results suggest that: (a) there are sensors within the neuropil which respond to change of [Na+] and influence Na appetite, and that these changes of [Na+] are induced deep within the neuropil by those saccharides which do not cross the blood-brain barrier or enter cells; change of CSF[Na+] alone is not sufficient to alter appetite but a change in brain extracellular fluid (ECF)[Na+] is probably necessary; (b) the theory is advanced that the stimulus for altered Na intake could be altered brain ECF[Na+] producing a change in cerebral intracellular fluid (ICF)[Na+] of the sensors; and (c) phlorizin, in reducing or blocking Na-coupled glucose transport, could increase Na appetite by producing a fall in ICF[Na+] of the specific neurones subserving sodium appetite or prevent a decrease in Na appetite caused by IVT infusion of hypertonic NaCl by preventing an increase in ICF[Na+] of this same neuronal system.

Animals↗
PubMed1989

The 1H NMR visibility of intracellular lactate in Streptococcus faecalis.

1H NMR studies of glycolysis in washed cell suspensions of Streptococcus faecalis indicated that intracellular lactate is not 1H NMR visible. Evidence for this was gained from time course studies of glycolysis at increasing concentrations of glucose. A close correlation existed between the relative increase in the lactate integral and the enzymatically determined extracellular lactate concentration [Lo]. When ionophores which cause the collapse of the positive intracellular/extracellular lactate gradient were added to cell suspensions following fermentation of 5, 10 and 50 mM glucose, the increase in the lactate integral was proportional to the respective increase in [Lo]. A more direct method for determining the origin of the lactate signal involved centrifugation of a cell suspension after fermentation of 50 mM glucose and measurement of lactate in the extracellular and intracellular fluid. 1H spectra of the cell suspension, supernatant and sonicated pellet revealed that the lactate observed in the cell suspension was equivalent to the lactate in the supernatant alone. The intracellular lactate contained in the pellet represented 42% of the total lactate, indicating that only 58% of lactate is detected by in vivo 1H MRS of S. faecalis. This result is in contrast with the high percentage (70-90%) of in vitro lactate which is detected by in vivo 1H MRS of mammalian brain tissue (Williams S. R. et al. Magn. Res. Med. 7, 425-431, 1988). This may be due to a higher proportion of extracellular lactate in mammalian tissue or differences in the intracellular environments of bacterial and mammalian cells.

Enterococcus faecalis↗
PubMed2002

Skeletal muscle regulates extracellular potassium.

Maintaining extracellular fluid (ECF) K(+) concentration ([K(+)]) within a narrow range is accomplished by the concerted responses of the kidney, which matches K(+) excretion to K(+) intake, and skeletal muscle, the main intracellular fluid (ICF) store of K(+), which can rapidly buffer ECF [K(+)]. In both systems, homologous P-type ATPase isoforms are key effectors of this homeostasis. During dietary K(+) deprivation, these P-type ATPases are regulated in opposite directions: increased abundance of the H,K-ATPase "colonic" isoform in the renal collecting duct drives active K(+) conservation while decreased abundance of the plasma membrane Na,K-ATPase alpha(2)-isoform leads to the specific shift of K(+) from muscle ICF to ECF. The skeletal muscle response is isoform and muscle specific: alpha(2) and beta(2), not alpha(1) and beta(1), levels are depressed, and fast glycolytic muscles lose >90% alpha(2), whereas slow oxidative muscles lose ~50%; however, both muscle types have the same fall in cellular [K(+)]. To understand the physiological impact, we developed the "K(+) clamp" to assess insulin-stimulated cellular K(+) uptake in vivo in the conscious rat by measuring the exogenous K(+) infusion rate needed to maintain constant plasma [K(+)] during insulin infusion. Using the K(+) clamp, we established that K(+) deprivation leads to near-complete insulin resistance of cellular K(+) uptake and that this insulin resistance can occur before any decrease in plasma [K(+)] or muscle Na(+) pump expression. These studies establish the advantage of combining molecular analyses of P-type ATPase expression with in vivo analyses of cellular K(+) uptake and excretion to determine mechanisms in models of disrupted K(+) homeostasis.

Animals↗
PubMed1985

Phorbol esters and horseradish peroxidase stimulate pinocytosis and redirect the flow of pinocytosed fluid in macrophages.

Lucifer Yellow CH (LY) is an excellent probe for fluid-phase pinocytosis. It accumulates within the macrophage vacuolar system, is not degraded, and is not toxic at concentrations of 6.0 mg/ml. Its uptake is inhibited at 0 degree C. Thioglycollate-elicited mouse peritoneal macrophages were found to exhibit curvilinear uptake kinetics of LY. Upon addition of LY to the medium, there was a brief period of very rapid cellular accumulation of the dye (1,400 ng of LY/mg protein per h at 1 mg/ml LY). This rate of accumulation most closely approximates the rate of fluid influx by pinocytosis. Within 60 min, the rate of LY accumulation slowed to a steady-state rate of 250 ng/mg protein per h which then continued for up to 18 h. Pulse-chase experiments revealed that the reduced rate of accumulation under steady-state conditions was due to efflux of LY. Only 20% of LY taken into the cells was retained; the remainder was released back into the medium. Efflux has two components, rapid and slow; each can be characterized kinetically as a first-order reaction. The kinetics are similar to those described by Besterman et al. (Besterman, J. M., J. A. Airhart, R. C. Woodworth, and R. B. Low, 1981, J. Cell Biol. 91:716-727) who interpret fluid-phase pinocytosis as involving at least two compartments, one small, rapidly turning over compartment and another apparently larger one which fills and empties slowly. To search for processes that control intracellular fluid traffic, we studied pinocytosis after treatment of macrophages with horseradish peroxidase (HRP) or with the tumor promoter phorbol myristate acetate (PMA). HRP, often used as a marker for fluid-phase pinocytosis, was observed to stimulate the rate of LY accumulation in macrophages. PMA caused an immediate four- to sevenfold increase in the rate of LY accumulation. Both HRP and PMA increased LY accumulation by stimulating influx and reducing the percentage of internalized fluid that is rapidly recycled. A greater proportion of endocytosed fluid passes into the slowly emptying compartment (presumed lysosomes). These experiments demonstrate that because of the considerable efflux by cells, measurement of marker accumulation inaccurately estimates the rate of fluid pinocytosis. Moreover, pinocytic flow of water and solutes through cytoplasm is subject to regulation at points beyond the formation of pinosomes.

Animals↗
PubMed1962

Partitioning of body fluids in the Lake Nicaragua shark and three marine sharks.

The relative volumes of major body fluids of freshwater and marine sharks are remarkably similar in spite of the differences in external medium and in osmotic pressure of body fluids. The small differences detected are in agreement with differences reported in comparisons of freshwater and marine teleosts: a slightly higher total water content and a smiller ratio of extracellular to intracellular fluids in freshwater forms.

Animals↗
PubMed1982

Viscoelastic properties of sickle cells and hemoglobin.

The quantitative relationship between deoxygenation and rheological behavior of SS cell suspensions and concentrated HbS solutions has been studied under steady shear (viscosity eta) and oscillatory shear (complex viscosity with viscous component eta' and elastic component eta"). decrease of O2 saturation below 80-85% causes eta, eta' and eta" to increase progressively in SS cell suspensions and HbS solutions. These rheological parameters do not change in AA cell suspensions and HbA solutions following deoxygenation. The deoxygenation-induced increase in eta" of HbS solutions from the unmeasurable level when oxygenated reflects the gelation of HbS. At high O2 saturations, the rheological behavior of the intracellular fluid has relatively insignificant contribution to that of the SS cell suspension. As O2 saturation decreases, the viscoelastic properties of the SS cell suspension become increasingly dominated by that of the intracellular HbS. at a given degree of deoxygenation, eta, eta' and eta" of HbS solutions decrease with increasing shear rate, indicating that HbS aggregates can be dispersed by shear stress.

Anemia, Sickle Cell↗
PubMed1992

[Heterotopic heart transplantation in the rat: an experimental method for evaluating myocardial protection].

This research represents the first part of a project finalized to prolong the ischemic time of the explanted heart. Our experimental model utilizes rat hearts heterotopically transplanted into the abdomen of a recipient: a denervated heart but perfused by blood as to permit a good evaluation of the reperfusion damage. We used 3 different types of cardioplegic solutions to achieve cardiac arrest: the first of the intracellular fluid type, the second of the extracellular type and the third one as a standard cardioplegic solution supplemented by Ca++ antagonist. Cold saline 4 degrees C was used as control. Histological patterns, birefringence index and intracellular content of high energy phosphates were evaluated. Specimens were taken after 1 hour of ischemic time and after 1 hour of reperfusion. Early results show that administration of cardioplegic solution maintains birefringence index and preserve high energy phosphates: among the 3 different types of solution the intracellular type seems to achieve better results although the number of experiments is too small to show any statistical significance. These data show that this model is appropriate to test cardioplegic solutions and their effectiveness.

Abdomen↗
PubMed1983

Solute equilibrium over the extracellular fluid space in haemorrhagic hypotension: a study in a cannulated thoracic duct model.

Haemorrhagic hypotension, 50 mm Hg, has been inflicted on non-starved rats. Osmolar and solute developments have been followed in lymph and arterial plasma to assess diffusion and equilibration characteristics of the initial stages of haemorrhage. Lymph flow changes have reflected an intracellular fluid mobilization to the interstitium, caused by an osmotic gradient due to the elevated levels of glucose. A fluid homeostatic effect of pseudodiabetes associated with stress and haemorrhage is postulated.

Animals↗
PubMed1984

Nutritional assessment by isotope dilution analysis of body composition.

The three components of body mass, body cell mass (BCM), extracellular fluid (ECF), and fat + extracellular solids (ECS: bone, tendon, etc) can be quantified using established isotope dilution techniques. With these techniques, total body water (TBW) and ECF are measured using 3H2O and 82Bromine, respectively, as tracers. BCM is calculated from intracellular fluid (ICF) where ICF = TBW - ECF. Fat + ECS is estimated as: body weight - (BCM + ECF). TBW and ECF can be determined by either of two calculation methods, one requiring several timed plasma samples (extrapolation method) and one requiring a single plasma sample and a 4-h urine collection (urine-corrected method). The comparability of the two calculation methods was evaluated in 20 studies in 12 bone marrow transplant recipients. We found that for determination of TBW and ECF there was a very strong linear relationship (r2 greater than 0.98) between the calculation methods. Further comparisons (by t test, 2-sided) indicated that for the determination of ECF, the methods were not significantly (p greater than 0.90) different; however, TBW determined by the urine-corrected method was slightly (0.1 to 6%), but significantly (p less than 0.01) greater than that determined by the extrapolation method. Therefore, relative to the extrapolation method, the urine-corrected method "over-estimates" BCM and "under-estimates" fat + ECS since determination of these compartment sizes depends on measurement of TBW. We currently use serial isotope dilution studies to monitor the body composition changes of patients receiving therapeutic nutritional support.

Adipose Tissue↗
PubMed1985

Volume and density changes of biological fluids with temperature.

High-precision (10(-5) g/ml) mass density measurements on human blood, plasma, plasma ultrafiltrate (using PM-10 membranes), and erythrocyte concentrate samples were performed with the mechanical oscillator technique. Measurement temperatures varied between 4 and 48 degrees C and were accurate to +/- 1 X 10(-2) K. The coefficient of thermal expansion (beta), defined as relative volume change with temperature, was calculated. It was shown that beta increases with temperature in these fluid samples over the entire temperature range investigated; the magnitude of this increase declines with increasing temperature; beta increases with density at temperatures below 40 degrees C but is independent of density above 40 degrees C; and the beta of the intracellular fluid has about twice the value of the beta for extracellular fluid at low (4-10 degrees C) temperatures but is equal for both fluids at greater than or equal to 40 degrees C. The mechanical oscillator technique provides data with an accuracy sufficient to perform precise (10(-5) K) calculations of beta of small volumes of biological fluids.

Blood Volume↗
PubMed1996

Hemodynamic, plasma volume, and prenodal skin lymph responses to varied resuscitation regimens.

The theoretical efficacy of hypertonic saline (HS) resuscitation for hemorrhagic shock purportedly stems from the osmolar extraction of intracellular fluid into the plasma. This hypothesis presumes a concomitant expansion of the interstitial fluid space. Colloid resuscitation, in theory, expands the plasma volume by extracting interstitial fluid. These hypotheses were tested in a canine-modified Wigger's model of hemorrhagic shock. Forty, male, splenectomized dogs were anesthetized and instrumented. Animals underwent a baseline equilibration period followed by shock for 120 minutes. Each animal was randomized to one of four groups and received equal amounts of Na+ either as lactated Ringer's (LR) solution, 10% dextran 40 (Dex) in normal saline, 7.5% saline (HS), or 7.5% saline plus Dex (HSD). Parameters measured at baseline, shock, and at postresuscitation 30 minutes, 60 minutes, 90 minutes, and 120 minutes, included: mean pressure (MAP), output, pulmonary capillary wedge pressure, prenodal skin lymph flow, serum and lymph albumin, wet-to-dry skin ratios, and plasma volume. MAP, cardiac output, and plasma volume were most quickly restored with LR and Dex resuscitation (MAP = 106 and 118 mm Hg) compared to HS and HSD (MAP = 98 and 92 mm Hg). Lymph flow and lymph albumin flux were best restored with LR and HSD (mean = 85 and 48 microL/min) compared to Dex and HS (mean = 36 and 37 microL/min). Wet/dry skin ratios were greatest at 60 minutes in the LR group but similar at 120 minutes in all four groups. These data suggest that interstitial fluid space remains contracted during the first hour after HS, HSD, and Dex resuscitation compared with LR resuscitation, even though the restoration of plasma volume, MAP, and cardiac output is greatest with the Dex regimen. Further studies with total body water and intracellular water are needed in this model.

Animals↗