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Biomedical subjects

R Dyer

Publications and source records attributed to R Dyer.

14 recordsLinked to original sources
PubMed1991

5-lipoxygenase inhibitory activity of zileuton.

Zileuton [N-(1-benzo[b]thien-2-ylethyl)-N-hydroxyure] inhibited 5-hydroxyeicosatetraenoic acid synthesis by rat basophilic leukemia cell 20,000 x g supernatant and rat polymorphonuclear leukocytes (PMNL) (IC50 = 0.5 and 0.3 microM) respectively. It also inhibited leukotriene (LT)B4 biosynthesis by rat PMNL (IC50 = 0.4 microM), human PMNL (IC50 = 0.4 microM) and human whole blood (IC50 = 0.9 microM). Inhibition of human PMNL LTB4 biosynthesis was removed readily by a simple wash procedure. At concentrations up to 100 microM, the compound produced little or no inhibition of several related enzymes, such as platelet 12-lipoxygenase, soybean and rabbit reticulocyte 15-lipoxygenase and sheep seminal vesicle cyclooxygenase. At p.o. doses from 0.5 to 5 mg/kg in the dog, zileuton produced a rapid and sustained inhibition of ex vivo blood LTB4 biosynthesis which correlated with the pharmacokinetic behavior of the compound. In a similar ex vivo study in the rat, the compound displayed an p.o. ED50 of 2 mg/kg. Zileuton was highly effective in preventing 6-sulfidopeptide LT formation in the rat peritoneal cavity triggered by an antigen-antibody reaction with an ED50 of 3 mg/kg. In experimental models of inflammation, zileuton significantly reduced arachidonic-acid induced mouse ear edema (ED50 = 31 mg/kg) and also attenuated inflammatory cell accumulation in the rat pleural Arthus reaction. The effectiveness of this compound for preventing LT formation in vitro, ex vivo and in vivo suggests its utility for preventing the pathophysiological effects of the LTs and other 5-lipoxygenase products in animals and in humans.

Administration, Oral↗
PubMed1990

Fluid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.

Animals↗
PubMed1988

Electrophysiological measures of visual and auditory function as indices of neurotoxicity.

The application of auditory and visual evoked potentials (VEP) to neurotoxicity testing of humans and animals is reviewed. VEPs elicited by flash, reversing-checkerboard patterns, and sine wave grating are described. The flask evoked potential in rats is altered by exposure to many heavy metals, pesticides and solvents. The brainstem auditory evoked potential also appears to be sensitive to neurotoxic chemicals, but the evidence available is limited. The homology of auditory and visual evoked potentials in rats and humans is useful for cross-species extrapolation in neurotoxicology research.

Animals↗
PubMed1987

Experiential factors in the expression of hypermotility produced by intradentate colchicine: lack of effect of GM1 ganglioside on colchicine-induced loss of granule cells and mossy fibers.

Adult male Fischer-344 rats were given bilateral injections of 2.5 micrograms colchicine or artificial cerebrospinal fluid into caudal and rostral sites of the dentate gyrus of the hippocampus. One group of rats received 21 consecutive daily injections of 20 mg/kg GM1 gangliosides, i.p., beginning the day prior to surgery. Another group received saline. Colchicine-induced hypermotility was not seen in animals repeatedly handled 21 d after surgery, in spite of significant decreases in granule cell number and decreases in the volume of hippocampal mossy fibers. Pretreatment with GM1 had no effect on behavior and it did not protect against the hippocampal damage produced by colchicine. Rats given colchicine, but not handled for 21 d, showed significant hypermotility, which was associated with decreases in hippocampal granule cells. These data underscore the importance of handling in postlesion functional recovery.

Animals↗
PubMed1987

Radiation exposure to patients during extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy is rapidly becoming an accepted treatment of renal calculi. Since fluoroscopy is involved to image the stones it is important to know how much radiation the patient receives during this proCedure. Surface radiation exposure to the patient was measured in more than 300 fluoroscopic and radiographic procedures using thermoluminescent dosimeters. Initial results showed an average skin exposure of 10.1 rad per procedure for each x-ray unit, comparing favorably with exposure rates for percutaneous nephrostolithotomy and other routine radiological procedures. Factors influencing exposure levels include stone characteristics (location, size and opacity), physician experience and number of shocks required. Suggestions are given that may result in a 50 per cent reduction of radiation exposure.

Humans↗
PubMed1985

Balloon dilatation of the prostatic urethra. Work in progress.

Balloon dilatation of the prostatic urethra was performed in eight dogs and one human with benign prostatic hyperplasia. This was done in vivo in six dogs and in vitro in two dogs and one human. Follow-up study at 1-23 weeks showed persistent dilatation, which was documented both radiographically and pathologically. Technical improvements limited complications to the early phase of the study. While results are encouraging, extrapolation to humans is difficult.

Animals↗
PubMed1975

An electron microscopic study of the effects of portacaval shunts on the ultrastructure of the rat liver after partial hepatectomy.

The normally quiescent stable adult liver has a generous capacity for reparative hypertrophy and hyperplasia after loss of functional tissue. The large reserve of the liver's functional capacity permits survival of the animal even if over 70 per cent of its liver is removed. It retains an inherent capacity for regenerative growth which subsides once the original organ deficit is restored. This study attempted to resolve the question of whether alteration in hepatic hemodynamics affects the regenerative stimulus of the liver after partial (70 per cent) hepatectomy. It has shown that the liver remnant regenerates after reduction of portal blood flow by construction of a portacaval anastomosis. The diversion of blood from the liver exerts its own histologic and electron microscopic effects on the liver. Reduction of portal blood flow affects the temporal patterns of regeneration after partial hepatectomy but does not prevent completion of the regenerative process. Correlation of this study with the biochemical data available in the literature indicates that the structural changes in the cellular organelles during the process of regeneration reflect dynamic biochemical events that are based on a predetermined genetic code representing the key to life that is uniquely found in the liver.

Animals↗
PubMedDate not supplied

A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium.

A single and multiple oral dose administration study of meclofenamate sodium (Meclomen) was conducted in ten healthy male volunteers. An initial 300 mg oral dose on day 1 was followed by a 100 mg every 8 h dosage regimen on study days 4 through 18. Intensive plasma and urine sample collection was carried out over the first three study days, and for 120 h following administration of the final dose on day 18. Plasma and urine specimens were analyzed by a specific HPLC assay for unconjugated meclofenamic acid and metabolites I and II of meclofenamic acid before and after sample incubation with beta-glucuronidase. Meclofenamic acid was rapidly absorbed following oral dose administration. Concentrations of meclofenamic acid existed primarily as unconjugated drug in plasma, with only a small amount present in the conjugated form. Meclofenamic acid was rapidly eliminated, with an elimination half-life of approximately 1.3 h. This resulted in no detectable accumulation upon multiple dose administration. Metabolite I, which is one-fifth as active as meclofenamic acid in in vitro inhibition of cyclooxygenase, was present in unconjugated form at steady state in concentrations approximately 50 per cent of those of meclofenamic acid, as unconjugated drug. The majority of metabolite I in plasma existed as glucuronide conjugate. Metabolite II, which is inactive, was present in very significant concentrations in unconjugated form. Plasma protein binding determinations conducted on meclofenamic acid and metabolite I indicated that the free fraction of metabolite I was 8.7 to 10.9 times higher than that of meclofenamic acid. When the lower activity and lower steady state concentrations, but higher free fraction, are considered, it would appear that metabolite I may contribute significantly to the in vivo inhibition of cyclooxygenase activity seen after administration of meclofenamic acid.

Adult↗