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F Barker

Publications and source records attributed to F Barker.

16 recordsLinked to original sources
PubMed1992

Uptake of a protein-bound polar compound, acetaminophen sulfate, by perfused rat liver.

The hepatocytic entry of acetaminophen sulfate conjugate was examined in the rat liver, perfused with red cells with and without albumin, by use of the multiple-indicator dilution technique. [3H]acetaminophen sulfate was injected into the portal vein in a bolus of blood containing 51Cr-labeled red blood cells (a vascular reference), sucrose (a low-molecular-weight interstitial reference) or 125I-labeled albumin (a high-molecular-weight interstitial reference, included when albumin was present), and the time courses of their outflow into the hepatic venous blood were observed. The [3H]acetaminophen sulfate, which binds partially to albumin, emerged between albumin and sucrose in the presence of albumin, processed the upslope of the sucrose curve and showed a late low-in-magnitude tailing; the precession disappeared in the absence of albumin. Biliary excretion of [3H]acetaminophen sulfate was less than 1% of the dose. Quantitative evaluation with a barrier-limited, space-distributed variable transit time model (including rapidly equilibrating albumin binding) accounted for the albumin effect on [3H]acetaminophen sulfate behavior and demonstrated a low liver cell permeability for the acetaminophen sulfate and a small interstitial binding space for its nonalbumin-bound fraction in excess of that for sucrose, which in the absence of albumin was of similar dimensions.

Acetaminophen↗
PubMed1991

Esterases for enalapril hydrolysis are concentrated in the perihepatic venous region of the rat liver.

Perfusion of substrate via only the hepatic artery with simultaneous substrate-free perfusion of portal vein or hepatic vein [hepatic artery portal vein-hepatic artery hepatic vein] was used to examine the enzymic distribution of carboxylesterases towards the hydrolysis of enalapril to enalaprilat in the perfused rat liver preparation. In this single-pass method, [14C]enalapril was delivered by the hepatic artery at 2 ml/min into the liver, whereas drug-free perfusate entered the portal vein or hepatic vein at 10 ml/min for HAPV and HAHV perfusions, respectively. During steady state, a multiple indicator dose of 51Cr-labeled red blood cells (vascular marker), [58Co]EDTA (interstitial space marker, which behaves similarly to labeled tracer sucrose), and 3H2O was given into the hepatic artery. Labeled enalapril and the reference indicators entering via the hepatic artery will reach virtually all sinusoidal spaces during HAPV, and will be confined to the peripheral region during HAHV. By defining the steady-state extraction ratios of enalapril (Etot) and segregating the components of biliary excretion and metabolism, and by assessing the intracellular water spaces and the corresponding transit times during HPAV and HAHV, the metabolic sequestration rate constant (metabolic intrinsic clearance per unit accessible cell water space) for the periportal region/whole liver (HAHV/HAPV) was 0.344. The data suggest that the carboxylesterase activity for enalapril conversion to enalaprilat is primarily localized in the perihepatic venous region of the rat liver.

Animals↗
PubMed1990

Transfer of enalaprilat across rat liver cell membranes is barrier limited.

The liver cell entry of enalaprilat, the polar, pharmacologically active dicarboxylic acid metabolite arising from esterolysis of enalapril, a new angiotensin-converting enzyme inhibitor, was examined in the perfused rat liver by use of the multiple-indicator dilution technique. [Phenylpropyl-2,3-3H]enalaprilat was injected into the portal vein in a bolus of blood containing 51Cr-labeled red blood cells (a vascular reference) and 125I-labeled albumin and [14C]sucrose (interstitial references that do not enter cells), with observation of the time courses of their outflow into the hepatic venous blood. A quantitative evaluation of the data was carried out by use of the barrier-limited, space-distributed variable transit time model (C.A. Goresky, G.G. Bach, and B. E. Nadeau, J. Clin. Invest. 52:991-1009, 1973). For data up to 60 s after injection, the transfer coefficients for influx, efflux, and sequestration were 0.018 +/- 0.004 (means +/- SD), 0.044 +/- 0.017, and 0.033 +/- 0.007 s-1, respectively. The influx permeability surface area product (influx clearance) per gram was 0.0057 +/- 0.0013 ml.min-1.g-1, and the rapidly accessible cellular equilibrium distribution space for enalaprilat was 0.137 +/- 0.022 ml water/g wet wt. At times beyond 60 s, the fitted data deviated systematically from the experimental data, suggesting the presence of an additional intracellular pool. With this addition, the coefficients for transfer between the intracellular pools were 0.0150 +/- 0.0045 s-1 for the direction cytoplasmic pool (pool 1)----additional pool (pool 2) and 0.0234 +/- 0.0069 s-1 for the opposite direction, and the fitted volumes of pools 1 and 2 became 0.126 +/- 0.021 and 0.082 +/- 0.018 ml/g, the total accessible cellular distribution space became 0.208 +/- 0.036 ml/g wet wt, and the sequestration transfer coefficient became 0.027 +/- 0.007 s-1. The data indicate that, as previously postulated (I. A. M. de Lannoy and K. S. Pang, Drug Metab. Dispos. 14: 513-520, 1986), the enalaprilat flux across liver cell membranes is retarded by a diffusional barrier. The results also indicate that enalaprilat is excluded from part of the volume of hepatocytes, as expected for an anionic compound crossing the membrane in charged rather than protonated form, given the negative electrical potential of the cytosol vs. the extracellular space.

Animals↗
PubMed1990

[14C]urea and 58Co-EDTA as reference indicators in hepatic multiple indicator dilution studies.

The space distribution and the processes underlying uptake of tracer substrate may be appraised by the multiple indicator dilution technique, after the simultaneous injection of noneliminated vascular (51Cr-labeled red blood cells), extracellular (125I-labeled albumin and [14C]sucrose for high and low molecular weight interstitial space, respectively), and cellular (3H2O) indicators and tracer substrate. When tracer substrates and/or their metabolites containing 14C or 3H labels are being studied, it becomes necessary to find substitutions for the similarly labeled noneliminated indicators. In red blood cell-perfused rat livers, 58Co-EDTA is found to be a good replacement for the low molecular weight interstitial reference; it has a space distribution indistinguishable from that for [14C]sucrose. [14C]urea and 3H2O, which distribute similarly in red blood cells, have similar outflow dilution profiles. With corrections for minor deviations in recovery [a ratio of 0.936 +/- 0.024 (SD)] and transit time [a ratio of 0.962 +/- 0.008 (SD)], the cellular water space can be closely approximated from the [14C]-urea curve. 58Co-EDTA and [14C]urea are reasonable substitutes for [14C]sucrose and 3H2O, respectively, in multiple indicator dilution liver perfusion studies for investigating transfer and removal characteristics of tracer substrates.

Animals↗
PubMed1986

Semi-quantitative gallium-67 lung scanning as a measure of the intensity of alveolitis in pulmonary sarcoidosis.

Gallium-67 (67Ga) lung scanning has been applied for some years in pulmonary sarcoidosis to assess the activity of the alveolitis. Interpreting the scans, however, is difficult due to the low uptake of 67Ga in the disease process relative to background activity. In this study we have measured the mean parenchymal lung activity of 67Ga and have compared the lung activity to that at three remote sites, the liver, the abdomen and the thigh. The results obtained were compared with the percentage of lymphocytes in broncho-alveolar lavage fluid. There was a very good correlation with the lung-to-thigh uptake measurements and a much poorer correlation with the lung-to-liver and the lung-to-abdomen measurements. It was observed that steroid therapy reduced dramatically the correlation between the broncho-alveolar lavage findings and the 67Ga scan measurements. The results suggest that in patients not on steroid therapy, the 67Ga lung-to-thigh measurements may be used, similarly to the broncho-alveolar lavage lymphocyte counts, to identify those with high-intensity alveolitis from those with low-intensity alveolitis.

Adult↗
PubMed1986

A comparison between four simple methods for measuring glomerular filtration rate using technetium-99m DTPA.

Numerous centers perform glomerular filtration rate (GFR) measurements on patients undergoing renal imaging with Tc-99m DTPA. GFR measurement, however, does involve multiple blood samples taken over a 4-hour period, and this has led to attempts to simplify the technique by reducing the number of blood samples required and hence diminish the time taken to perform the test and the inconvenience to the patient. Four different simplified techniques for measuring GFR that have been reported in the literature are compared with a reference 2 blood sample method. Three of the methods do not require any blood samples but have standard errors of greater than 20 ml/min in adults and greater than 14 ml/min in children. The other method requires one blood sample, and if this is taken at 2 hours postinjection, the standard error is 9 ml/min in adults and 5 ml/min in children. The latter method is suitable for routine use in renography when accuracy is not of paramount importance.

Adult↗
PubMed1986

GFR measurement by simulating constant infusion with data acquired using a CdTe detector. A feasibility study.

Conventional nuclear medicine methods for measuring glomerular filtration rate, GFR, are invalidated if the initial injection of radiopharmaceutical is tissued. An analytical method proposed by Veall and Gibbs in 1982 overcomes this difficulty but does require multiple blood samples. This paper investigates whether it is feasible to use the analytical method on data acquired with a CdTe detector system and thereby reducing to one the number of blood samples required. Synthetic data were used to investigate the effect of (a) duration of sampling (b) statistical noise and (c) non-stationarity on the GFR values derived by the Veall and Gibbs method. A sampling duration of 100 min is shown to be adequate and statistical noise is not a limiting factor. However, data fluctuations, mainly due to detector motion, do reduce the accuracy of the method. When the analytical technique is applied to data obtained using a CdTe detector on 40 patients the GFR values are similar to those derived by the conventional method (r = 0.957, Syx = 9.1 ml min-1). The technique is sufficiently attractive to warrant further studies to establish its absolute accuracy.

Computer Simulation↗
PubMed1981

Implementing a competency-based orientation program.

Competency-based orientation is efficient and effective. It allows individual learning needs to be met without sacrificing achievement of consistent standards. The system does require a large initial investment in the development of learning options and assessment of evaluation tools. It also requires the commitment of nurse managers and administrators to the concept and the implementation process. Orientation is still complex and expensive at Maryland General, but now it meets individual needs and is cost-effective.

Clinical Competence↗
PubMedDate not supplied

The effect of chilli ingestion on gastrointestinal mucosal proliferation and azoxymethane-induced cancer in the rat.

Of the three main races of Singapore, Malays and Indians are less susceptible to gastric and colorectal carcinoma and peptic ulcer when compared with Chinese. Racial differences in dietary habits include a smaller amount of chilli consumed by the Chinese when compared with the other two races. Chilli may be expected to accelerate gastrointestinal transit and hence to inhibit colonic carcinogenesis, while its active ingredient capsaicin protects against experimental gastric mucosal injury. The effect of chilli consumption was studied in relation to: (i) gastrointestinal crypt cell production rate and nucleic acid content as indices of mucosal proliferation, which is related to the risk of development of gastrointestinal cancer and peptic ulcer; and (ii) azoxymethane-induced intestinal cancer. Sprague-Dawley rats (n = 102) received either standard powdered chow or chow supplemented with 100 or 200 mg of chilli powder daily for 1, 18 or 24 weeks. Gastric, small-bowel and colonic crypt cell production rates were studied at all three time periods, while mucosal DNA, RNA and protein contents were measured at 1 and 24 weeks. While crypt cell production rates were unaffected by chilli ingestion, mucosal contents of nucleic acid and protein were mostly increased in chilli-fed animals compared to controls, especially in the colon at 24 weeks. A further 99 rats received subcutaneous injections of either azoxymethane 15 mg/kg/week x 6 or sterile water and were randomized to the same three dietary groups for 26 weeks. The number, size and location of benign and malignant duodenal and colonic tumours were unaffected by chilli intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗