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At least 811 records · Page 45Linked to original sources
PubMed1999

Interaction of a plasma-sprayed hydroxyapatite coating in contact with human osteoblasts and culture medium.

The loss of calcium from plasma-sprayed calcium phosphate ceramics (CPCs) on bioinert metal substrate (Ti-6Al-4V) immersed in cell culture medium with or without human osteoblast culture was measured. The ceramics were a CPC and a duplex system composed of a CPC layer on an alumina coating. The dissolution of calcium compounds was monitored by measuring the calcium leaked from the coatings into the culture medium in 15 days. Calcium was measured by flame photometry. The surfaces of the ceramics exposed to the culture medium and in contact with osteoblasts were analysed by X-ray diffraction (XRD). The dissolution process occurred in the first 6 days of contact, but the calcium released into the culture medium was only a small fraction of the calcium content of the coatings. The presence or absence of osteoblasts on the surface of the ceramics did not make significant difference for the calcium release. The XRD spectra of the ceramics before and after immersion and in contact with cells did not show a significant change in the compounds of the coatings.

Aerosols↗
PubMed1993

Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies.

BACKGROUND: The growth of microscopic tumor lesions at or beyond treatment field margins poses a major problem in the diagnosis and treatment of cancer. Early detection techniques that clearly define the location or field spread of disease may improve the planning of disease treatment. METHODS: In vivo fluorescence photometry is a non-imaging technique that digitally displays relative fluorescence values in volts proportional to the luminescence intensity detected by a silicon photodiode. The sensitivity of the instrument has allowed the detection of micrometastases in preclinical studies. RESULTS: Statistical analysis demonstrates that the photosensitizer Photofrin (dihematoporphyrin ether and/or ester) (Quadra Logic Technologies, QLT, Vancouver, B.C., Canada), currently used for photodynamic therapy, administered in doses lower than those used in clinical studies, is useful for the detection of occult disease. With the drug doses used, cutaneous photosensitivity was avoided in the animal models tested. The results in Lobund-Wistar rats with transplantable prostatic adenocarcinoma (PA-III) demonstrated the utility of this technique in detecting clinically occult disease, with a prediction rate of approximately 94% with drug doses as low as 0.25-0.5 mg/kg. CONCLUSIONS: With the use of the hamster buccal cavity model involving the initiation and promotion of premalignant and malignant conditions by 9,10 dimethyl-1,2-benzanthracene, the technique could discern these two stages of disease with significance levels that were less than 0.05 and 0.01, respectively.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2002

Influence of the emulsion components and preparation method on the laboratory-scale preparation of o/w emulsions containing different types of dispersed phases and/or emulsifiers.

Emulsification is a complex process, strongly influenced by emulsion composition as well as by preparation procedure, and the characterisation of emulsions with regard to their structure and stability can be carried out with many different methods. To evaluate the influences of emulsion composition and preparation procedure on the structure and properties, oil-in-water emulsions were prepared using the model dispersed phase dodecane and the surfactant Tween on the one hand and the real food components sunflower oil (dispersed phase) and casein (emulsifier) on the other hand. The emulsions were prepared in a small laboratory-scale with a turbo-mixer alone and in combination with ultrasonic treatment. The emulsion activity was measured by photometry, the emulsion stability was evaluated visually and the droplet size was determined by laser particle analysis. The results of the investigations made with the model substances agree only partly with those made with the real food substances. For the model emulsions strong correlation were found between the emulsion activity and the particle sizer data because of the high purity and the defined structure of the model substances. On the contrary, for the emulsions made with the real food components sunflower oil and sodium caseinate the correlation were much weaker. Therefore a proper characterisation of the structure and properties of food emulsions requires examinations with several methods which are independent from each other. Furthermore, for laboratory-scale emulsification the combination of turbo-mixer and ultrasonic treatment is suitable to obtain small droplets and a narrow droplet distribution also for very small emulsion volumes.

Emulsions↗
PubMed1999

Chloroquine uptake, altered partitioning and the basis of drug resistance: evidence for chloride-dependent ionic regulation.

The biochemical mechanism of chloroquine resistance in Plasmodium falciparum remains unknown. We postulated that chloroquine-resistant strains could alter ion fluxes that then indirectly control drug accumulation within the parasite by affecting pH and/or membrane potential ('altered partitioning mechanism'). Two principal intracellular pH-regulating systems in many cell types are the amiloride-sensitive Na+/H+ exchanger (NHE), and the sodium-independent, stilbene-sensitive Cl-/HCO3- antiporter (AE). We report that under physiological conditions (balanced CO2 and HCO3-) chloroquine uptake and susceptibility are not altered by amiloride analogues. We also do not detect a significant difference in NHE activity between chloroquine-sensitive and chloroquine-resistant strains via single cell photometry methods. AE activity is dependent on the intracellular and extracellular concentrations of Cl- and HCO3- ions. Chloroquine-resistant strains differentially respond to experimental modifications in chloride-dependent homeostasis, including growth, cytoplasmic pH and pH regulation. Chloroquine susceptibility is altered by stilbene DIDS only on chloroquine-resistant strains. Our results suggest that a Cl(-)-dependent system (perhaps AE) has a significant effect on the uptake of chloroquine by the infected erythrocyte, and that alterations of this biophysical parameter may be part of the mechanism of chloroquine resistance in P. falciparum.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1983

Time-dependent excretion of lithium, sodium, potassium, rubidium, magnesium and strontium in the urine of a multiple sclerosis patient.

Field desorption mass spectrometry and stable isotope dilution have been used for direct trace analysis of metals in urine. Samples were collected over 24 h at 2 h intervals from a hospitalized multiple sclerosis patient. Quantitative determinations of Li+, Rb+, Mg2+ and Sr2+ from individual samples have been made and correlated with the amounts of urine excreted as well as with the time of day. The concentrations of Na+ and K+ were determined by flame photometry. The quantities of metals excreted in urine during the course of 24 h were 0.0129 mg for lithium, 4700 mg for sodium, 2100 mg for potassium, 1.4 mg for rubidium, 78.8 mg for magnesium and 0.2356 mg for strontium. The maximal absolute quantities excreted of all metals determined correspond with the largest volume of urine. The highest amounts of potassium, rubidium and strontium were found in urine during the daytime (8.00-20.00), whilst magnesium was excreted increasingly during the night hours (20.00-8.00). The excretion of lithium and sodium is fairly even over the entire 24 h period. It is noteworthy that similarities in the excretion profile and the concentration course are observed between Li+ and Na+ on one hand and between K+ and Rb+ on the other. Moreover, the lower concentration of Rb+ ions in urine of multiple sclerosis patients, in comparison to healthy individuals and clinical controls as reported previously, was confirmed.

Adult↗
PubMed2003

Monitoring the cellular surface display of recombinant proteins by cysteine labeling and flow cytometry.

A general method is described that allows one to follow the surface display of recombinant proteins in Escherichia coli without having to use specific antibodies or enzymatic reactions. The method is based on cysteine-specific labeling through Michael addition to the double bond of maleimide and its derivatives, and takes advantage of the fact that naturally occurring surface proteins in E. coli contain no accessible cysteine residues. The method is easy to perform and could be simply applied to different analytic procedures including Western blot, spectral photometry, and flow cytometry. By using this new labeling method, single cells bearing a distinct protein at the surface could be selected by fluorescence-activated cell sorting. The data were obtained by using autodisplay, an efficient surface display system established for E. coli, but the method presented here represents rather a general solution for analyzing the surface display of recombinant proteins, independent of the cellular system used.

Adrenodoxin↗
PubMed1984

Nuclear DNA cytophotometry in prostate carcinoma.

Eighty patients with prostate carcinoma underwent fine-needle aspiration biopsy for cytologic grading and DNA-single-cell fluorescence photometry before and at 6-month intervals after endocrine treatment. The histograms of DNA values showed single peaks and bimodal and scattered distributions which correlated to the different tumor grades before therapy. The DNA values were significantly different from the controls with benign prostatic hypertrophy. After start of therapy, regressive changes of the DNA-histograms were increases of diploid and hypodiploid DNA values and disappearance of secondary peaks. Progressive changes were increased scattering of DNA values and appearance of secondary peaks. Progressive changes in the histograms were closely related to clinical remission and stable disease, but related poorly to clinical progression. The survival correlated with the pretherapeutic DNA-histograms and with the DNA-median, third-quartile, and maximum parameters.

DNA, Neoplasm↗
PubMed1990

Quantification of the DNA content of structurally abnormal X chromosomes and X chromosome aneuploidy using high resolution bivariate flow karyotyping.

Quantification of the Hoechst and chromomycin A3 fluorescence intensities of mitotic human chromosomes isolated from karyotypically normal and abnormal cells was performed with a dual beam flow cytometer. The resultant flow karyotypes contain information about the relative DNA content and base composition of chromosomes and their relative frequencies in the mitotic cell sample. The relative copy number of X and Y chromosomes was determined for 38 normal males and females and 6 cell lines with X or Y chromosome aneuploidy. Flow karyotype diagnoses corresponded with conventional cytogenetic results in all cases. We show that chromosome DNA content can be derived from peak position in Hoechst vs. chromomycin flow karyotypes. These values are linearly related to propidium iodide staining intensity as measured with flow cytometry and to the binding of gallocyanin chrome alum to phosphate groups as measured with slide-based scanning photometry. Cell lines with deleted or dicentric X chromosomes ranging in length from 0.53 to 1.95 times normal were analyzed by using flow cytometry. The measured difference in DNA content between a normal X and each of the structurally abnormal chromosomes was linearly correlated to the difference predicted from cytogenetics and/or probe analyses. Deletions of 3-5 Mb, which were at and below the detection limits of conventional cytogenetics, could be quantified by flow karyotyping in individuals with X-linked diseases such as Duchenne muscular dystrophy, choroideremia, and ocular albinism/ichthyosis. The results show that the use of flow karyotyping to quantify the size of restricted regions of the genome can complement conventional cytogenetics and other physical mapping techniques in the study of genetic disorders.

Aneuploidy↗
PubMed2003

Characterization and quantitation of mixtures of alkyl ether sulfates and carboxylic acids by capillary electrophoresis with indirect photometric detection.

The separation, characterization, and determination of mixtures of alkyl ether sulfates (AES) and fatty acids (C10-C16) in background electrolytes (BGEs) containing acetonitrile (ACN)-water mixtures is addressed. Due to inhibition of the ionization of the carboxylate groups, the migration time and the resolution between the fatty acids decreased when the water content of the BGE was reduced, but efficiency and resolution between the AES oligomers improved. The migration times increased and resolution improved by substituting 5% ACN by an equivalent amount of dioxane. A complete separation of the two surfactant classes, up to the AES oligomers with 8 ethylene oxide units (EOs) with respect to C10, with excellent resolution between the AES oligomers, while preserving a satisfactory resolution between the fatty acids, was achieved with a BGE containing 5 mM trimethoxybenzoic acid, 7 mM dipentylamine, 85% ACN, 5% dioxane, and 10% water. The two surfactant classes were increasingly resolved by further reducing the water content of the BGE. Thus, C2 (acetate) was resolved from the AES oligomers up to 7 EOs using 90% ACN and 5% dioxane, but the resolution between the heavier fatty acids was poor with this BGE. Identification of the AES oligomers was eased by the excellent regularity of the successive migration times; thus, within each AES subclass or series of oligomers with the same number of carbon atoms in the alkyl chain, the migration times decreased following a mild curve as the number of EOs increased. The way how the data obtained by indirect photometry (corrected peak areas that are proportional to the molar concentrations) should be managed to avoid systematic error when the calibration curve is constructed using an AES standard with an oligomer distribution different from that of the samples is discussed and equations are given. Decyl sulfate was successfully used as internal standard. The detection limits (S/N = 3) were of ca. 2 microM for individual AES oligomers.

Alkanesulfonates↗
PubMed1992

Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver.

The effects of increases in cytosolic Ca2+ on hepatocyte bile secretion are unknown. A number of agents that alter levels of cytosolic Ca2+ in the hepatocyte also produce hepatic vasoconstriction and activate protein kinase C, which complicates interpretations of their effects on bile secretion. To better understand the role of cytosolic Ca2+ in bile secretion, we examined the effect of the Ca2+ ionophore A23187 (0.1 mumol/L), the Ca2+ agonist vasopressin (10 nmol/L) and the Ca(2+)-mobilizing agent, 2,5-di(tert-butyl)-1,4-benzohydroquinone (25 mumol/L) on cytosolic Ca2+ in isolated hepatocytes and on bile flow in the isolated perfused rat liver, using vasodilators and inhibitors of protein kinase C and Ca2+ influx. Single-pass perfused livers were used, and cytosolic Ca2+ was measured by luminescent photometry in isolated hepatocytes loaded with the Ca(2+)-sensitive photoprotein aequorin. After A23187 perfusion, a sustained 74% +/- 10% (mean +/- S.D.) decrease in bile flow and a sustained 271% +/- 50% increase in perfusion pressure was observed. Simultaneous pretreatment with the vasodilator papaverine (25 mumol/L) and the protein kinase C inhibitor H-7 (50 mumol/L) abolished the pressure increase but not the decrease in bile flow, whereas pretreatment with Ni2+ (25 mumol/L) to block the influx of extracellular Ca2+ markedly reduced both the pressure increase and the decrease in bile flow. Vasopressin produced a transient (mean = 6 min) 75% +/- 4% decrease in bile flow and a sustained 7% +/- 4% increase in perfusion pressure. Pretreatment with H-7 alone corrected the vasopressin-induced pressure increase but also failed to eliminate the decrease in bile flow, whereas pretreatment with Ni2+ decreased the magnitude of the decrease by two-thirds without affecting the increase in perfusion pressure, 2,5'-di(tert-butyl)-1,4-benzohydroquinone produced a transient 65% +/- 20% decrease in bile flow and a transient 56% +/- 15% increase in perfusion pressure. In isolated hepatocytes, bromo-A23187, the nonfluorescent form of the ionophore, produced a sustained 56% +/- 32% increase in the cytosolic Ca2+ signal, whereas vasopressin resulted in a transient 241% +/- 75% increase and 2,5-di(tert-butyl)-1,4-benzohydroquinone resulted in a sustained 149% +/- 66% increase. The ionophore-induced increase in Ca2+ was abolished completely by pretreatment of the hepatocytes with Ni2+, whereas the vasopressin-induced increase was reduced by 38%.(ABSTRACT TRUNCATED AT 400 WORDS)

Aequorin↗
PubMed2003

Formation and growth of clusters in conventional and new kinds of simulated body fluids.

Simulated body fluid (SBF) with ion concentrations approximately equal to those of human blood plasma has been widely used for the in vitro assessment of the bioactivity of artificial materials and for the formation of bonelike apatite on various substrates. Ion concentrations of conventional SBF (c-SBF) are, however, not exactly equal to those of blood plasma, and hence the apatite formed in c-SBF is not the same as bone apatite in its composition and structure. Recently, the present authors prepared new kinds of SBFs (r-SBF, i-SBF, and m-SBF) with ion concentrations nearer to those of blood plasma. The r-SBF and i-SBF have ion concentrations equal to those of blood plasma in total and dissociated amounts, respectively. The m-SBF has ion concentrations equal to those of blood plasma in total amount except for the HCO(-) (3) concentration, which was set to the saturated level with respect to calcite. In the present study, the stabilities of c-SBF, r-SBF, i-SBF and m-SBF were examined in terms of cluster formation in the fluids by means of dynamic light scattering photometry. The c-SBF and m-SBF were found to form only calcium phosphate clusters, whose initial hydrodynamic diameter was approximately 1 nm, and this did not change with storage time at 36.5 degrees C. Besides the calcium phosphate clusters, r-SBF and i-SBF formed calcium carbonate clusters, whose initial hydrodynamic diameters were 10-30 nm, and these increased significantly with storage time. The formation and growth of calcium carbonate clusters in r-SBF and i-SBF can be attributed to their supersaturation with respect to calcite. These indicate that r-SBF and i-SBF lack long-term stability. The m-SBF is recommended for the assessment of bioactivity of artificial materials as well as the formation of bonelike apatite on various substrates from the viewpoint of stability as well as similarity to blood plasma.

Apatites↗
PubMed1982

Ion regulation in potassium-sensitive mutants of Paramecium tetraurelia.

Two recessive mutations of Paramecium tetraurelia confer sensitivity to potassium: While wild-type cells survive when up to 30 mM KCl is added to their growth medium, mutants cease to grow and die when levels of added KCl reach 20-25 mM. Similar sensitivities are seen to Rb+ and Cs+, but not to Na+. Swimming behavior of mutants is indistinguishable from wild type when placed in stimulating solutions containing Na+, K+, or Ba2+. Behavioral adaptation to low levels of K+ also is indistinguishable from wild type. Flame photometry reveals that one mutant is unable to keep out K+ and Na+ when those ions are at low levels in the medium. Both mutants have markedly lower internal Na+ than does wild type. Problems with K+ permeability account for the sensitivity of the one mutant to elevated external K+, but the basis of sensitivity in the other mutant is unclear. These mutants expand the range of ion regulation mutants in Paramecium and demonstrate that lesions in cellular ion regulation in this organism need not result in changes in swimming behavior.

Animals↗
PubMed1986

Volume changes in activated human neutrophils: the role of Na+/H+ exchange.

The apparent volume of neutrophils, as measured electronically with the Coulter counter, has been reported to increase upon treatment with chemotactic factors. The occurrence of a volume change was confirmed by forward angle light scattering and by isotopic measurements of intracellular water space in cells treated with 12-O-tetradecanoylphorbol 13,acetate (TPA) or formyl-methionyl-leucyl-phenylalanine (FMLP). Cell swelling was associated with an increase in the osmotic content of the cells, determined from Boyle-van't Hoff plots, and with an increase in Na+ content, measured by flame photometry. The volume change was inhibited by replacement of extracellular Na+ with K+ or N-methyl-D-glucamine+, or by addition of amiloride. Swelling was also inhibited by the 5-N-substituted analogs of amiloride, which are potent specific inhibitors of the Na+/H+ antiport. This pathway is activated in neutrophils by both TPA and FMLP. Activation of Na+/H+ exchange, determined as a Na+ -dependent and amiloride-sensitive cytoplasmic alkalinization, was also found when neutrophils were treated with hypertonic solutions. The hypertonic activation of the antiport was similarly followed by cell swelling, detectable by electronic sizing. The results indicate that activation of Na+/H+ exchange can lead to significant cell swelling in neutrophils.

Calcium↗
PubMed2004

Age-dependent changes of the periodontal ligament in rats.

Even after the end of the natural tooth eruption, there is a continuous renewal of the periodontal collagenous fiber system, depending on functional demands. The aim of this study was to analyse the age-dependent changes and regional differences of the collagen renewal rate of the periodontal ligament in healthy rats. The study was performed by autoradiography of the molars of rats aged 1, 8, and 18 months, where collagen was labelled by intravenously applied 3H-proline. After an 8-hour incorporation period, the animals were killed. For comparative examinations, molar roots were subdivided into cervical, middle, and apical thirds. Structural and quantitative analyses were performed by light microscopy and autoradiography, using an image-analysing computer-assisted operating unit that determined the 3H-proline-labelled collagen by photometry based on extinction measurement. With increasing age of the animals, the number of silver grains (3H-proline-blackened collagen) was reduced and the quantitative evaluation indicated a reduction of 3H-proline in the periodontal ligament. The lowest level of 3H-proline activities was observed in the middle, and the highest level in the apical root third, independent of age. All preparations revealed condensations of silver grains, which were located in the region of the periodontal ligament adjacent to the alveolar bone, but did not reveal any preferred position with regard to the dental topography. With progressive age, the uptake of 3H-proline in the periodontal ligament was reduced by about 20 to 30%, a result that corresponds to a decrease in collagenous fiber production. Collagen was mainly formed in the apical and cervical root third, starting from the alveolar bone side, presumably in response to functional strain.

Aging↗
PubMed2003

The fall and rise of active chloride transport: implications for regulation of intraocular pressure.

Early study of transepithelial salt transfer focused on Cl(-) and not Na(+), partly because Cl(-) was readily measureable. The advent of flame photometry and tracer techniques brought Na(+) to the fore, especially since short-circuited frog skin (Rana temporaria) produces baseline net movement of Na(+) and not of Cl(-). Zadunaisky was among the first to describe what is currently termed secondary active Cl(-) transport, helping stimulate interest in Cl(-) handling by other tissues, notably the thick ascending limb of the loop of Henle important in renal counter-current multiplication. More recently, molecules responsible for electroneutral and electrogenic Cl(-) transfer have been cloned, and specific diseases resulting from their faulty expression have been identified. The clinical importance of transepithelial Cl(-) transfer is illustrated by studies of aqueous humor formation by the eye's bilayered ciliary epithelium. NaCl is taken up from the stroma by the pigmented ciliary epithelial (PE) layer, diffuses through gap junctions into the nonpigmented ciliary epithelial (NPE) layer, and is released into the aqueous humor largely through Na(+) pumps and Cl(-) channels. ATP released by NPE cells can be ecto-enzymatically metabolized to adenosine. Adenosine can mediate paracrine/autocrine stimulation of Cl(-) channels and aqueous humor secretion by occupying A(3) adenosine receptors (ARs). A(3)AR agonists indeed elevate, and A(3)AR antagonists lower, intraocular pressure (IOP) in wild-type mice. A(3)AR knockout mice have low IOP and their responses to A(3)AR agonists and antagonists are blunted; this suggests that reducing Cl(-)-channel activity with A(3)AR antagonists may provide a novel approach for treating glaucoma.

Animals↗
PubMedDate not supplied

Oligonucleotide labelled lipase as a new sensitive hybridization probe and its use in bio-assays and biosensors.

Radiolabelled polynucleotide probes have been employed extensively for the detection of complementary nucleic acids by specific hybridization. Within the last few years, various methods have been developed using enzyme-labelled probes to avoid unstable and hazardous isotopes. These assays, based on photometry, fluorescence, and chemiluminescence, have helped to overcome the use of radioactive probes. To increase the performance of a non-radioactive DNA detection system, the labelling enzyme should remain stable under hybridization conditions which allow the formation of a 15-25 bp long DNA-DNA duplex (Tm = 50-70 degrees C). Therefore, the use of unstable phosphatase and peroxidase conjugates must be avoided due to the composition of the hybridization mixture and the high temperature. By screening various hydrolytic enzymes to fit the special demands, fungal lipases turned out to be the most practical. They offer high sensitivity due to an extremely high turnover number, stability at room temperature for several years, thermostability under working conditions and an easy design of various chromogenic, fluorescent and electrochemical active substrates. Several types of silanized, oxidized and unmodified metal sensors and also standard microtitre plates modified with amino groups were used for the immobilization of oligonucleotides. A sandwich hybridization using the lipase-labelled oligonucleotide probe and a terminal immobilized capture DNA on a microtitre plate or sensor surface combined with a rapid hybridization in solution simplifies and improves the performance of the DNA detection system.

Alkaline Phosphatase↗
PubMedDate not supplied

Clearance of gadolinium chelates by hemodialysis: an in vitro study.

Although the gadolinium (Gd)-chelates currently approved for clinical use in the United States are considered "readily dialyzable," the actual clearance rates have not been published. The purpose of this study was to establish in vitro dialysis clearance rates of Gd-chelates to develop rational strategies for removing the agents with dialysis. Three agents, Gd-diethylenetriaminopentaacetic acid (Gd-DTPA), Gd-HP-DO3A and Gd-DTPA-BMA were diluted separately in plasma and saline and were dialyzed by using a clinical dialyzer unit with a commercially available capillary filter at rates of 0-300 cc/min. Predialyzer and postdialyzer concentrations were determined by inductively coupled atomic emission photometry. Urea and creatinine clearance rates also were determined. The clearance rate for Gd-chelates were considerably lower than that of urea and creatinine, which are generally considered benchmarks of dialysis efficiency. At 300 cc/min flow rates, the clearances were (clearance in cubic centimeters per minute with 95% confidence interval): Gd-DTPA-74 cc/min (68-80 cc/min) delta-HP-DO3A 67 cc/min (63-71cc/min); and Gd-DTPA-BMA 67 cc/min (63-71cc/min). In comparison, urea and creatinine were 180 cc/min (178-181 cc/min) and 142 cc/min (124-131 cc/min), respectively. There was no difference between clearance rates of Gd-chelates in saline and plasma, implying there was no protein binding. By using a first order kinetic model of dialysis time, more than 12.2 to 14.7 hours of dialysis would be necessary to remove 97% of the injected dose of Gd-chelate.(ABSTRACT TRUNCATED AT 250 WORDS)

Contrast Media↗
PubMed1980

Preliminary evaluation of furosemide-probenecid interaction in humans.

The pharmacokinetics and pharmacodynamics of intravenous furosemide, 40 mg, were studied in four healthy male subjects in a crossover fashion with and without probenecid pretreatment. In each study, 16 plasma and 10 urine samples were collected over 24 hr. Fluid and electrolyte urinary losses were replaced orally throughout the study. Unchanged furosemide and probenecid were measured using high-pressure liquid chromatography; urinary sodium was measured by flame photometry. Although probenecid caused marked changes in the pharmacokinetic parameters of furosemide (increased area under the curve, decreased plasma and renal clearance, increased half-life, and decreased fraction excreted unchanged in the urine), there was no significant difference in its gross 8-hr natriuretic and diuretic effect. However, analysis of the time course of natriuresis showed a pattern similar to that of the urinary furosemide excretion rate, whereas the plasma concentration was poorly correlated over the entire dose-response curve.

Adult↗