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Biomedical subjects

W M Williams

Publications and source records attributed to W M Williams.

At least 55 records · Page 3Linked to original sources
PubMed1984

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. A. Effect on the permeability to sodium fluorescein.

Significantly elevated levels of sodium fluorescein (MW 376) were found only in the brains of conscious rats made considerably hyperthermic (colonic temperatures greater than 41.0 degrees C) by exposure to ambient heat (42 +/- 2 degrees C) for 90 min or 2450 MHz CW microwave energy at 65 mW/cm2 (SAR approximately equal to 13.0 W/kg) for 30 or 90 min. For microwave-exposed rats, fluorescein levels within the cortex and hypothalamus appeared to increase with increasing duration of exposure. This trend was not apparent in the cerebellum or medulla. Exposure to ambient heat resulted in increased fluorescein with the cortex, hypothalamus and medulla, but not the cerebellum, and, in general, ambient heat was not as effective as microwave energy in raising tracer concentrations within the brain. By far the greatest elevation of fluorescein dye in the brain occurred in those animals whose blood-brain barrier had been opened osmotically by intracarotid injection of 10 M urea. It is suggested that increased levels of sodium fluorescein found in the brain tissue of ambient heat and microwave-exposed rats most likely represent technically derived artifact and not a breakdown of the blood-brain barrier.

Animals↗
PubMed1984

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. B. Effect on the permeability to HRP.

Alteration of blood-brain barrier (BBB) permeability by 2450 MHz CW microwaves was assessed semi-quantitatively after intravenous injection of horseradish peroxidase (HRP) and exposure of conscious, unrestrained rats to incident power densities of 0, 20 or 65 mW/cm2 for 30, 90 or 180 min. Additional rats were exposed to ambient heat (42 +/- 2 degrees C) for 30 or 90 min. None of the brain regions studied, with the exception of the normally leaky pineal gland, showed extracellular HRP leakage attributable to microwave or thermally-induced breakdown of the blood-brain barrier. The mean ratio of HRP-labeled microvessel endothelium/total number of microvessels counted was determined for each brain region. Mean values for the cortex, hypothalamus, cerebellum and medulla of microwave-exposed and heated rats were consistently below those of corresponding sham levels. This decrease appeared to correlate inversely with power density and duration of exposure. Statistically significant deviation (P less than 0.05) from sham mean values occurred in the cortex, hypothalamus, cerebellum and medulla of animals made hyperthermic with ambient heat or exposure to microwaves at 65 mW/cm2 (specific absorption rate approximately equal to 13.0 W/kg) for 30 or 90 min. Additionally, electron microscopic evaluation of ultrathin sections taken from each of the 4 brain regions revealed no significant extravasation of HRP indicative of microwave or ambient heat-induced disruption of the blood-brain barrier.

Animals↗
PubMed1984

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. C. Effect on the permeability to [14C]sucrose.

Intravenously injected [14C]sucrose was used as a small molecular weight (342 daltons), hydrophilic tracer for determination of 2450 MHz CW microwave and ambient heat effects on rat blood-brain barrier permeability in the cerebral cortex, hypothalamus, cerebellum and medulla. The tracer was injected 4 min following exposure of conscious, unrestrained rats to microwaves at 0 or 65 mW/cm2 for 30 or 90 min (SAR approximately equal to 13.0 W/kg) or to ambient heat (42 +/- 2 degrees C) for 90 min. Comparison of mean permeability-surface area products (PA) and uptake ratios between sham and microwave-exposed animals revealed a statistically significant (P less than 0.05) decrease of both PA and uptake ratios for the hypothalamus, cerebellum and medulla of rats exposed to microwaves for 30 min. This decrease was not apparent for rats exposed to microwaves for 90 min. A pertinent observation, with regard to this latter group of animals, was the increased circulating levels of the tracer when colonic temperature was raised to approximately 41.4 degrees C or higher.

Animals↗
PubMed1984

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. D. Brain temperature and blood-brain barrier permeability to hydrophilic tracers.

Measurement of temperature within the cerebral cortex, hypothalamus, cerebellum and medulla of rats sham-, heat- or microwave-exposed revealed the presence of a thermal gradient within the brain. In all groups, cerebral cortex and the cerebellum were cooler than the deeper hypothalamus and medulla. Exposure to 2450 MHz CW microwaves or ambient heat (42 +/- 2 degrees C) resulted in measurable elevation of regional brain temperature, but without alteration of temperature gradients normally observed within the brain. Exposure to 20 mW/cm2 (SAR approximately equal to 4 W/kg) for 30, 90 or 180 min induced a small, but significantly (U = 0, P less than 0.05) increased temperature of the colon, and in each region of the brain studied. Exposure to an incident power density of 65 mW/cm2 (SAR approximately equal to 13.0 W/kg) for 30 or 90 min or to ambient heat (42 +/- 2 degrees C) for 90 min resulted in a substantially greater thermal response as indicated by higher colonic and brain temperatures. Comparison of regional brain temperature with individual colonic temperatures is expressed as delta T = t degrees Cbrain--t degrees Ccolon. In general delta T values for ambient heat or microwave-exposed rats did not differ significantly from those of sham-exposed animals. Exposure to microwaves or ambient heat did not alter the general relationships between regional brain and colonic temperatures, i.e., cortical and cerebellar temperatures were always below and hypothalamic and medullary temperatures always above corresponding colonic temperatures. The plotted temperature data (brain vs colonic temperature) indicate a linear relationship between brain and colonic temperatures. Levels of sodium fluorescein (NAFl), horseradish peroxidase (HRP) and [14C]sucrose (described in preceding papers) within the brain show a high correlation (P less than 0.05) with brain temperature. Suppression of blood-brain barrier permeability to hydrophilic tracers was most pronounced at brain temperatures exceeding approximately 40 degrees C and is demonstrated to be temperature dependent.

Animals↗
PubMed1984

Effect of penicillin on the renal tubular secretion of methotrexate in the monkey.

The effect of penicillin on the renal tubular secretion of methotrexate (MTX) in rhesus and cynomolgus monkeys was studied in vivo and in vitro. In stop-flow experiments in ketamine-anesthetized monkeys, the ratios of urine/plasma MTX concentration to urine/plasma inulin concentration of proximal tubular samples were about 2-fold greater than the base-line free-flow values of 3.3 to 4.8, indicating net proximal tubular secretion. MTX secretion was inhibited by penicillin, which lowered the base-line U/PMTX/U/Pinulin ratios to 0.8 to 1.3; the effect persisted over a 30-min period after discontinuation of penicillin administration. Penicillin also slowed the disappearance of MTX from plasma over a 2-hr period after i.v. bolus administration of MTX. In experiments with renal cortical slices, MTX uptake at 25 degrees was linear over the initial 30 min. The uptake Km and Vmax were 0.09 mM and 0.11 mumol/g of tissue/30 min, respectively. Penicillin competitively inhibited MTX uptake; the Ki was 0.83 mM. MTX efflux from preloaded slices (incubated with 0.5 mM MTX for 45 min) was a first-order process with an initial t1/2 of 7.1 min, which decreased to 2.0 min in the presence of 1.36 mM penicillin. It was concluded that MTX and penicillin share a common secretory system in the kidney and that penicillin blocks MTX secretion by inhibiting cellular uptake and stimulating efflux.

Animals↗
PubMed1982

Effects of cimetidine on caffeine disposition in smokers and nonsmokers.

The absorption, distribution, and elimination of caffeine, 2 mg/kg by mouth, were evaluated in six smokers and six nonsmokers before and on the fourth day of administration of cimetidine, 300 mg by mouth every 6 hr. Caffeine absorption, assessed by the maximal serum caffeine concentration (C max) and the time to reach Cmax (t max), was very rapid relative to elimination. The total body clearance (TBC) of caffeine was higher (2.49 +/- 0.35 and 1.59 +/- 0.19 ml/kg/min, P less than 0.05) and the elimination half-life (t1/2) shorter (190 +/- 15 and 276 +/- 30 min, P less than 0.05) in smokers than nonsmokers, but Cmax, tmax, and the apparent volume of distribution (Vd, app) did not differ (P greater than 0.05). Cimetidine decreased the TBC of caffeine by 31% (to 1.73 +/- 0.28 ml/kg/min, P less than 0.05) and by 42% (to 0.92 +/- 0.11 ml/kg/min, P less than 0.01) in smokers and nonsmokers. The increases in t1/2 were 45% (to 276 +/- 25 min, P less than 0.05) and 96% (to 542 +/- 123 min, P less than 0.05). Cmax, tmax, and Vd, app were unaffected by cimetidine. Caffeine induced similar slight increases in blood pressure and pulse rate in smokers and nonsmokers both before and during cimetidine dosing.

Adult↗
PubMed1982

Renal tubular transport of folic acid and methotrexate in the monkey.

The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.

Animals↗
PubMed1981

Structural specificity in the renal tubular transport of tyrosine.

The structural requirements for aromatic amino acid reabsorption and secretion in the dog were investigated using a series of tyrosine analogs. In clearance experiments, l-tyrosine and l-phenylalanine underwent net reabsorption at rates 5 to 6 times greater than those of the corresponding d-enantiomers and about 1.5 time those of o- and m-dl-tyrosine. 3-(p-hydroxyphenyl)Propionic acid underwent net secretion under conditions of polyuria and high urinary pH and net reabsorption under conditions of oliguria and low pH. In stop-flow experiments, (U/Pl-amino acid)/(U/Pln) ratios, where U/P = concentration in urine and plasma and In = inulin, of proximal tubular samples were 1.5 to 5-fold greater than the control (free-flow) values of 0.1 to 0.3, indicating tubular secretion. Secretion was inhibited, and net reabsorption enhanced, by probenecid, p-aminohippuric acid and 2,4-dinitrophenol. (U/Pd-amino acid)/(U/PIN) ratios of proximal tubular samples were below the control values of 0.6 to 0.8, indicating tubular reabsorption. Probenecid had no effect on the overall pattern but caused a slight decrease in the relative clearance values. The stop-flow pattern of 3-(p-hydroxyphenyl)propionic acid excretion was similar to that of the I-amino acids. It was concluded that the I-amino acids undergo bidirectional transport and that the I-configuration and amino group are required for optimal active reabsorption, whereas ring hydroxylation has little effect on reabsorption transport. No absolute structural requirements for active secretion were elucidated.

Absorption↗
PubMed1977

Urinary prostaglandins: site of entry into renal tubular fluid.

The stop-flow technique was used in dogs to determine the site of entry of urinary prostaglandins (PG) into tubular fluid. The proximal tubule was localized by the peak (U/PPAH)/(U/PIn) and the distal tubule and collecting duct by the peak U/PIn and the minimum (U/PNa)/(U/PIn). The peak of prostaglandin E (PGE) concentration was located 4.8+/-0.8 (SEM) ml distal to the proximal tubule and 4.6+/-0.8 (SEM) ml proximal to the distal nephron. At its peak, PGE was concentrated 6.3-fold over baseline, whereas inulin was concentrated 1.4-fold at its peak. The height of the PGE peak but not its location was increased by an i.v. infusion of angiotensin II at 20 ng/kg of body wt per min. Indomethacin abolished the PG peak. In a single experiment, prostaglandin F2alpha (PGF2alpha) exhibited an excretion pattern similar to PGE. These data indicate that the site of entry of PG into tubular fluid is most likely in the loop of Henle. This is consistent with the hypothesis that PG synthesized in the medulla can be transported to the cortex via tubular fluid. Whether PG in the tubular fluid can influence renal function remains to be determined.

Animals↗