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Biomedical subjects

R Guillet

Publications and source records attributed to R Guillet.

At least 19 recordsLinked to original sources
PubMed1991

Neonatal exposure to therapeutic caffeine alters the ontogeny of adenosine A1 receptors in brain of rats.

Caffeine is a methylxanthine, commonly used in the premature neonate to treat apnea of prematurity. It is efficacious and appears to have few short-term side effects. An animal model, designed to mimic the developmental period in brain and level and duration of exposure in humans, was used to investigate possible long-term effects of early developmental exposure to caffeine on the ontogeny of the adenosine receptor to which caffeine binds. Specific binding at the adenosine A1 receptor, in five distinct regions of the brain was determined in rats, 14-90 days old, as a function of early postnatal exposure to caffeine, over days 2-6. In cortex, cerebellum and hippocampus but not in the brain stem or hypothalamus, there was an increase in specific binding, following neonatal exposure to caffeine, compared to specific binding in control animals. Kinetic analysis of binding to the A1 site in cortical tissue suggests that this increase was due to an increased maximum binding density (Bmax); binding affinity (Kd) did not change. Thus, limited exposure to caffeine, in the early neonatal period, may result in up-regulation of the adenosine A1 receptor that persists to young adulthood in the rat.

Animals↗
PubMed1991

Neonatal caffeine exposure alters developmental sensitivity to adenosine receptor ligands.

Studies were done to determine whether the apparent changes in behavioral sensitivity to adenosine receptor ligands that occur with age and with neonatal caffeine exposure were due to a change in sensitivity of the receptor for the ligand or to a more fundamental change in the receptor. Using an animal model that mimics the brain developmental period and level of caffeine exposure in human premature neonates treated with caffeine for apnea of prematurity, behavioral and neurochemical investigations were undertaken. The locomotor responses to acute challenge with caffeine (15, 30 and 60 mg/kg) and with D-phenylisopropyladenosine (D-PIA) (0.038 and 0.38 mg/kg), an adenosine receptor agonist, were measured in control and neonatally caffeine-exposed rats at 12, 15, 18, and 28 days of age. The dissociation constants (Kd) and maximal binding densities (Bmax) for agonist binding at the adenosine A1 receptor site were determined over a similar time period. Caffeine displacement of an adenosine A1 agonist was also measured to examine in vitro sensitivity to caffeine as a function of age and neonatal caffeine exposure. Our studies demonstrated that the differential responses to adenosine receptor ligands seen as a function of both age and neonatal caffeine exposure could not be overcome by merely increasing the doses of ligand administered. In addition, the results of the binding studies indicated that changes in the adenosine receptor are occurring as a function of age in different regions of the brain of control animals and that this development is influenced by neonatal caffeine exposure.

Adenosine↗
PubMed1991

Ultrasonic interferometry: study of particle sedimentation in liquid.

An ultrasonic interferometry method was designed to study sedimentation of particles in liquid. The method, based on A mode echography, measures the amplitude of ultrasonic waves reflected (echo E1) by a fixed interface I1 called "solid plate-sediment" interface formed when particles are sedimenting on a solid plate. The amplitude of the echo depends both on mechanical properties of the three media (solid plate, sediment and suspension) on the thickness of the sediment and on the presence of a second mobile interface I2 called "sediment-suspension" interface. In the first phase of sedimentation when the second interface is very close to the first, two reflected waves interfere. Then, in the second phase of sedimentation when the sediment is thick enough, the amplitude of the echo E1 depends only on the sediment and solid plate properties. The first phase will give information on the sedimentation rate of particles (SR). We have compared SR of particles determined by this method with SR measured in a cylindrical tube of the same geometry as the ultrasonic measurement cell and with theoretical values of the sedimentation rate given by theoretical models.

Interferometry↗
PubMed1991

Assessment of red blood cell aggregation with dextran by ultrasonic interferometry.

Aggregation of human red blood cells (RBCs) induced by dextrans of various molecular weight has been studied by using a new ultrasonic interferometry method. This method, based on A-mode echography, allowed for the measurement of the accumulation rate of particles on a solid plate which is related to their sedimentation rate (i.e., to their mean size). The initial aggregation process, the mean and the maximum sedimentation rate of aggregates and the packing of the sedimented RBCs have been investigated. Effects of hematocrit, molecular weight of dextrans and inhibition by dextran 40 on the RBC aggregation induced by dextran of higher molecular weight have been determined by analysing variations of the aggregate size. Results obtained confirm the aggregation effect of dextrans of molecular weights equal or higher than 70,000 dalton and disaggregation effect of dextran 40,000 dalton on aggregation by dextrans of higher molecular weight.

Dextrans↗
PubMed1990

Early developmental exposure to benzodiazepine ligands alters brain 31P-NMR spectra in young adult rats.

Alterations in brain high energy phosphate compounds, using 31P-NMR (nuclear magnetic resonance) spectroscopy, were measured in vivo in young adult (3-4 months) rats following prenatal exposure to ligands acting specifically at benzodiazepine (BDZ) binding sites. The exposure induced a decrease in intracellular pH that indicated a predominant interaction of the drugs in utero with central-type BDZ receptor sites. Late gestational exposure to BDZ ligands also induced changes in brain phosphocreatine (PCr) utilization. Exposure to the lowest dose of DZ (1.0 mg/kg) but not the higher dose (2.5 mg/kg) induced a significant change in PCr utilization. Exposure to the central-type BDZ receptor antagonist RO15-1788 alone clearly altered PCr utilization in adult offspring, and DZ (2.5 mg/kg) when administered concurrently was not able to prevent this effect. Though exposure to a peripheral-type ligand (PK11195) had no effect by itself, it converted the effect of the high dose of DZ to that of the low dose. Together, these results indicate an interaction during development between the central and peripheral-type BDZ binding sites on organization and/or regulation of cellular energy metabolism. Normalized ATP levels were not changed by any prenatal treatment indicating adequate buffering of intracellular ATP by phosphocreatine. The dopaminergic antagonist haloperidol did not alter intracellular pH or any index of phosphate metabolism indicating a selective receptor mediated role for BDZ ligands in influences on the long term organization of intracellular phosphate metabolism.

Animals↗
PubMed1990

Neonatal caffeine exposure alters adenosine receptor control of locomotor activity in the developing rat.

An animal model was developed to approximate the magnitude and brain developmental period of caffeine exposure experienced by the human infant receiving caffeine for apnea of prematurity. Serum levels of caffeine of 5-15 mg/l over the 24-hour period were achieved by administering to rat pups a loading dose of 20 mg/kg p.o. on day 2, followed by 15 mg/kg p.o. on days 3-6 of life. Locomotor activity, both spontaneous and following an acute challenge with D-phenylisopropyl adenosine (an adenosine receptor agonist, 10 mumol/kg i.p.) or caffeine (an adenosine receptor antagonist, 100 mumol/kg i.p.), was measured in 12-to 28-day-old native rat pups or pups neonatally exposed to caffeine. The stimulatory effect of acute caffeine on locomotor activity was developmentally delayed in neonatally exposed pups. It is postulated that early exposure to caffeine in some way altered the development of the central adenosine receptor control over locomotor activity.

Administration, Oral↗
PubMed1989

Determination of erythrocyte transit times through micropores. II. Influence of experimental and physicochemical factors.

A new red blood cell filtration system, termed the Cell Transit Time Analyzer (CTTA), has been developed in order to measure the individual transit times of a large number of cells through cylindrical micropores in special "oligopore" filters; the system operates on the electrical conductometric principle and employs special computer software to provide several measures of the resulting transit time histogram. Using this system with filters having pore diameters of 4.5 or 5.0 microns and length to diameter ratios of 3.0 to 4.7, we have evaluated the effects of several experimental factors on the flow behavior of normal and modified human RBC. Our results indicate: 1) linear RBC pressure-flow behavior over a driving pressure range of 2 to 10.5 cm H2O with zero velocity intercepts at delta P = 0, thus suggesting the Poiseuille-like nature of the flow; 2) resistance to flow or "apparent viscosities" for normal RBC which are between 3.1 to 3.9 cPoise and are independent of driving pressure and pore geometry; 3) increased flow resistance (i.e., increased transit times) for old versus young RBC and for RBC made less deformable by DNP-induced crenation or by heat treatment at 48 degrees C; 4) increased mean transit time and poorer reproducibility when using EDTA rather than heparin as the anticoagulant agent. Further, using mixtures of heat-treated and normal RBC and various percentile values of the transit time histogram, we have been able to demonstrate the presence of sub-populations of rigid cells and thus the value of measurements which allow statistical analyses of RBC populations.

2,4-Dinitrophenol↗
PubMed1988

Determination of erythrocyte transit times through micropores. I--Basic operational principles.

To study the transit times of each red blood cell passing through cylindrical micropores and in order to evaluate sub-population of cells with regard to their deformability, we have developed a new system called the cell transit time analyser (CTTA). By using an AC voltage (100 KHz) across a special filter, we measure the electrical conductance change produced by the cells passing through the pores under a known driving pressure. This computer based device provides the distribution of transit times tau for 2000 cells in 1 minute and as a result the mean transit time [tau]. Experiments with red cells were designed to evaluate the flow behavior of both normal cells and cells whose mechanical properties were artificially altered. Cell volume was changed by use of non-isotonic media. Cell shape and cell volume were modified by varying the pH of the suspending buffer. Results of these experiments are: 1) a skew distribution of transit times towards high tau values for both control cells and artificially altered cells is observed: 2) [tau] is minimum for isotonic conditions and increases sharply for either hypotonic or hypertonic media: 3) [tau] is minimum at physiological pH and increases for either acid or alcaline changes of pH.

Blood Flow Velocity↗
PubMed1988

Determination of erythrocyte transit times through micropores. II-- Influence of experimental and physicochemical factors.

A new red blood cell filtration system, termed the Cell Transit Time Analyzer (CTTA), has been developed in order to measure the individual transit times of a large number of cells through cylindrical micropores in special "oligopore" filters: the system operates on the electrical conductometric principle and employs special computer software to provide several measures of the resulting transit time histogram. Using this system with filters having pore diameters of 4.5 or 5.0 cm and length to diameter ratios of 3.0 to 4.7, we have evaluated the effects of several experimental factors on the flow behavior of normal and modified human RBC. Our results indicate : 1) linear PBC pressure - flow behavior over a driving pressure range of 2 to 10.5 cm H2O with zero velocity intercepts at delta P = 0, thus suggesting the Poiseuille - like nature of the flow; 2) resistance to flow or "apparent viscosities" for normal RBC which are between 3.1 to 3.9 cPoise and are independent of driving pressure and pore geometry; 3) increased flow resistance (i.e., increased transit times) for old versus young RBC and for RBC made less deformable by DNP-induced crenation or by heat treatment at 48 degrees C; 4) increased mean transit time and poorer reproducibility when using EDTA rather than heparin as the anticoagulant agent. Further, using mixtures of heat-treated and normal RBC and various percentile values of the transit time histogram. We have been able to demonstrate the presence of sub-populations of rigid cells and thus the value of measurements which allow statistical analyses of RBC populations.

Anticoagulants↗
PubMed1988

Anesthetic-induced corneal lesions in developmentally sensitive rats.

Developmental critical periods for the induction of abnormalities by exposure to exogenous substances need not be confined to the early embryonic stage of organogenesis. The combination of ketamine hydrochloride and xylazine, two commonly used anesthetic agents, resulted in a corneal epithelial calcium deposition in 84% of rat pups whose exposure was limited to a single injection during the third postnatal week only. Concurrent exposure to ketamine hydrochloride, xylazine, and yohimbine, an alpha 2 adrenergic receptor antagonist, resulted in corneal lesions in only 6% of rat pups so exposed. The etiology is presently not understood but may involve interference with neurally directed corneal development. Corneal desiccation may also play a role. Altered drug metabolism, and toxic interactions resulting from a changing oxygen or light milieu are less likely etiologic mechanisms. Aspects of corneal development and mechanisms by which drugs can interact with and disturb normal maturational sequences can now be approached.

Anesthetics↗
PubMed1988

In vivo 31P nuclear magnetic resonance measurement of chronic changes in cerebral metabolites following neonatal intraventricular hemorrhage.

The purpose of this study was to determine whether cerebral metabolic changes occur after intraventricular hemorrhage in the newborn. Five babies with bilateral grade 3 to 4 intraventricular hemorrhage were compared with 15 preterm infants without intraventricular hemorrhage. Cerebral high-energy phosphorus metabolites and intracellular pH were measured with in vivo 31P nuclear magnetic resonance spectroscopy. Spectra were collected initially within the first 2 weeks of life, and then every other week until discharged from the hospital. The phosphocreatine to inorganic phosphate ratio and the phosphocreatine to adenosine triphosphate ratio were significantly lower in the group with intraventricular hemorrhage, but differences in intracellular pH were not significant. Differences between babies with and without intraventricular hemorrhage varied with postconceptional age: in those with intraventricular hemorrhage, the phosphocreatine to adenosine triphosphate ratio was decreased at all postconceptional ages, and the phosphocreatine to inorganic phosphate ratio was lower in babies with intraventricular hemorrhage and younger than 30 weeks. Results of this study confirm the presence of chronic metabolic changes following intraventricular hemorrhage which may exacerbate neurologic damage after intraventricular hemorrhage in the newborn.

Adenosine Triphosphate↗
PubMed1978

Corticotropin responsiveness in the neonatal rat.

Plasma ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, subjected to treatment with either a median eminence extract with corticotropin releasing factor (CRF) activity or to ether exposure. 'CRF' injection elevated plasma ACTH levels on all days tested. Ether exposure elevated ACTH levels on days 14 and 21, but not on days 1 or 7. These results indicate: (1) that there is no diminution of responsiveness of the pituitary to direct stimulation by CRF as a function of age, and (2) that the mediators of the stress response above the level of the pituitary are not functionally mature until approximately day 14. Correlations with previous studies also indicate that there is a delay in the return of adrenal responsiveness until some time after these mediators attain maturity.

Adrenal Cortex↗