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Biomedical subjects

K D Pettigrew

Publications and source records attributed to K D Pettigrew.

At least 55 records · Page 3Linked to original sources
PubMed1982

Drug entry into and distribution within brain and cerebrospinal fluid: [14C]urea pharmacokinetics.

A four-compartment model was derived to analyze drug exchange among cerebral capillary plasma, cerebrospinal fluid (CSF), and the brain extracellular and intracellular (or bound) compartments. Equations that were derived incorporated the factor of cerebral blood flow. They were fit by nonlinear least squares to measured brain, plasma, and CSF (when available) concentrations of [14C]urea in the rat, in response to a step increase in plasma concentration, to intravenous infusion, or to a bolus injection of tracer. Best-fit values for the transfer constants were consistent among the three administrative regimens and agreed with published values, when available. Expressions also were derived and numerically evaluated for the lower limit of the brain extracellular space, for half times of brain [14C]urea uptake, and for the steady-state brain/plasma distribution volume. The model should make it possible to use transfer constants obtained for a given drug from one study (e.g., constant plasma concentration) to predict brain concentrations from measured plasma concentrations in other acute or chronic studies.

Animals↗
PubMed1980

Entry of opioid peptides into the central nervous system.

Cerebrovascular permeability of four modified opioid peptides--[D-Ala2]methionine enkephalin amide, beta-[D-Ala62,14C-Homoarg69]lipotropin 61 -69, alpha-[D-Ala2,14C-Homoarg9]endorphin, and beta-[D-Ala2,14C-Homoarg]endorphin--ranged from 1.4 to 3.9 X 10(-6) centimeters per second in brain regions of the conscous rat. These significant permeabilities should allow the peptides to fill the extracellular brain space with a half time of 3 to 11 minutes, as a result of a step increase in plasma concentration of unbound peptide.

Animals↗
PubMed1980

Quantitative aspects of reversible osmotic opening of the blood-brain barrier.

Retrograde infusion of a hypertonic arabinose solution into the right external carotid artery of rats reversibly increases cerebrovascular permeability to [14C]sucrose in the right cerebral hemisphere. PA ([14C]sucrose permeability x capillary surface area) rises from a control mean of 11 x 10(-6) S-1 to above 200 x 10(-6) S-1. The rise correlates with an increased staining of the brain by intravascular Evans blue, and is followed by a transient, 1-1.5% increase in brain water content. At least 20 s of infusion is required for 1.6 M arabinose solution to effectively open the blood-brain barrier. The increase in cerebrovascular permeability is temporary, however, because PA remains slightly elevated 1-2 h after infusion and is normal 6 h after infusion. It is suggested that osmotic barrier opening is mediated by cerebrovascular dilatation as well as by shrinkage of the vascular endothelium. By quantitatively defining thresholds of infusate concentration and infusion time for osmotic barrier opening, and by characterizing the time course of increased PA, the experiments establish criteria for applying the osmotic method to experimental pharmacology of the central nervous system.

Animals↗
PubMed1979

Successful separation of depressed, normal, and insomniac subjects by EEG sleep data.

Data from all-night EEG sleep studies were used to distinguish normal subjects, primary depressed patients, and primary insomniac patients. In part 1, we compared 41 normal subjects, 56 depressed patients, and 18 insomniacs. In a univariate comparison with normal subjects, depressed patients showed less total sleep, longer sleep latency, more early morning awake time, more intermittent awake time, less delta sleep, less sleep efficiency, and shorter rapid eye movement (REM) latencies; compared with insomniacs, depressed patients showed greater early morning awake time, shorter REM latency, greater REM index, and greater REM density. Using multivariate discriminant analysis, 82% of the sample were correctly classified by diagnosis: 100% of the normal subjects, 72% of the depressed patients, and 77% of the insomniacs. Eight variables contributed to the multivariate separation of depressed individuals from insomniacs and normals: total sleep time, total recording period, sleep efficiency, sleep latency, early morning awake time, awake time, REM time and REM%. When the discriminant functions were applied to a second group of 18 primary depressed patients, 82% were correctly classified as depressed. These results suggest that primary depressed patients and primary insomniac patients may show relatively characteristic patterns of sleep abnormality.

Adult↗
PubMed1979

Blood-brain barrier permeability in senescent rats.

Cerebrovascular permeability to 14C-sucrose was measured in 3-mo-old and 28-mo-old conscious, restrained Fischer 344 male rats. Tracer was injected intravenously in these animals and arterial plasma concentrations were followed for 50 to 240 min, when animals were killed and regional brain radioactivity was measured. Equations derived by a two-compartment diffusion model were fit to concentration data to estimate PA (product of cerebral capillary permeability and surface area) and Ve (cerebral distribution space of 14C-sucrose). PA in 3-mo-old rats averaged 7.53 x 10(-6) sec-1 in 14 cerebral regions, and was not significantly elevated in 28-mo-old rats except possibly at white matter. Ve fell from an average of 0.126 in control rats to 0.070 in 28-mo-old rats. This 45% reduction may reflect a reduced extracellular space in the older animals. The findings do not support the hypothesis that aging of the central nervous system is related to breakdown of the blood-brain barrier.

Aging↗
PubMed1979

REM architecture changes in bipolar and unipolar depression.

The authors compared total night sleep measures and REM sleep architecture values for normal control subjects (N = 36), unipolar depressed patients (N = 36), and bipolar depressed patients (N = 22). The unipolar and bipolar patients had significantly greater fragmentation of REM periods than control subjects, and bipolar patients showed greater fragmentation of REM periods than unipolar patients. In both the unipolar and bipolar samples, the duration of successive REM periods was related to the total number of REM periods during sleep.

Bipolar Disorder↗
PubMed1977

Osmotic opening of the blood-brain barrier in the rhesus monkey without measurable brain edema.

The blood-brain barrier in the rhesus monkey was opened to intravascular Evans blue-albumin, without causing brain edema or altering brain electrolytes, by perfusing 2.5 molal recrystallized D,L-lactamide into the internal carotid artery for 20--30 sec. Gross neurological and behavioral sequelae were absent in 7 of 8 animals with barrier opening, and 2 days after perfusion no statistically significant changes were observed in sodium, potassium or water contents of perfused as compared to unperfused gray and white matters of brains of the 7 normal animals. Brain endema may not have developed because parenchymal albumin was excreted or metabolized by 2 days. It is suggested also that closure of the barrier after several hours prevents salt from accompanying plasma fluid into the brain. Entry of fluid without salt would reduce, before measurable edema developed, any transcapillary osmotic gradient established by prior entry of plasma albumin.

Animals↗
PubMed1977

Quantitative evaluation of the loss of human platelet dense bodies following stimulation by thrombin or A23187.

1. Distributions of dense bodies per platelet were evaluated in unstimulated human platelets and in platelets stimulated to secrete by the addition of varying amounts of thrombin or the ionophore A23187. Since distributions were not Gaussian, they were compared by non-parametric methods. 2. Most distribution obtained following varying levels of dense-body release differed significantly from the control (unstimulated) distribution. In general, distribution from points widely separated in terms of per cent release of total dense-body content also differed significantly. Distributions obtained at points where the total number of dense bodies lost was approximately the same did not differ significantly, regardless of the drug and incubation conditions used to produce the dense-body loss. 3. Dense bodies were lose from platelets during the secretory process (measured as the release of either calcium or ATP), and the number of dense bodies lost correlated at a significant level with the amounts of both substances secreted. 4. Following maximal secretion produced by either thrombin or A23187, a population of dense bodies (refractory dense bodies) remained in platelets. The refractory dense bodies could not have been distributed uniformly among the control populations of either platelets or dense bodies. The distribution of refractory dense bodies could, however, be described by a model in which platelets containing large numbers of dense bodies had a greater proportion of their dense-body complement refractory than did platelets containing fewer dense bodies.

Adenosine Triphosphate↗
PubMed1976

A method to obtain infusion schedules for prescribed blood concentration time courses.

It is sometimes desirable to obtain a specified blood level which obeys a prescribed mathematical form. Following an approach based on impulse analysis via Laplace Transform techniques, a general method for an input injection schedule which will achieve this goal is derived. Specific infusion schedules are given which attain blood levels that are constant, increase linearly, decay exponentially, and increase exponentially. Further, simpler approximate infusion schedules are also derived whose outputs achieve the desired function after a short time. Two illustrative experimental examples-one for [14C]EDTA-Ca in anesthetized rhesus monkeys and the other for 2-deoxy-D-[1-14C]glucose in the conscious rat-are presented in detail. The assumptions are discussed and an error analysis is performed.

Animals↗