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Biomedical subjects

A M Mans

Publications and source records attributed to A M Mans.

At least 37 records · Page 2Linked to original sources
PubMed1987

Regional brain glucose use in unstressed rats after two days of starvation.

Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6-14C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation.

Animals↗
PubMed1987

Regional amino acid transport into brain during diabetes: effect of plasma amino acids.

Transport of phenylalanine and lysine into the brain was measured in 4-wk streptozotocin-diabetic rats to assess the effect on the neutral and basic amino acid transport systems at the blood-brain barrier. Amino acid concentrations in plasma and brain were also measured. Regional permeability-times-surface area (PS) products and influx were determined using a continuous infusion method and quantitative autoradiography. The PS of phenylalanine was decreased by an average of 40% throughout the entire brain. Influx was depressed by 35%. The PS of lysine was increased by an average of 44%, but the influx was decreased by 27%. Several plasma neutral amino acids (branched chain) were increased, whereas all basic amino acids were decreased. Brain tryptophan, phenylalanine, tyrosine, methionine, and lysine contents were markedly decreased. The transport changes were almost entirely accounted for by the alterations in the concentrations of the plasma amino acids that compete for the neutral and basic amino acid carriers. The reduced influx could be responsible for the low brain content of some essential amino acids, with possibly deleterious consequences for brain function.

Amino Acids↗
PubMed1986

Brain monoamines after portacaval anastomosis.

Norepinephrine, dopamine, and serotonin, as well as the serotonin metabolite, 5-hydroxyindoleacetic acid, were measured in whole-brain extracts from rats with a portacaval shunt or sham operation. Norepinephrine, serotonin, and 5-hydroxyindoleacetic acid were significantly higher after shunting. There was no difference in dopamine. The results support the idea that brain indole metabolism is increased during chronic hepatic encephalopathy. However, they provide evidence against suggestions that hepatic encephalopathy in general is accompanied by a shortage in the whole-brain content of the catecholamines norepinephrine and dopamine.

Animals↗
PubMed1986

Regional blood-brain barrier transport of glucose after portacaval anastomosis.

The regional influx of glucose across the blood-brain barrier was measured in rats 5 to 6 weeks after a portacaval anastomosis or sham operation. D-[14C]Glucose was infused intravenously for 15 sec while arterial blood was sampled continuously for measurement of plasma radioactivity and glucose concentration. Brain tissue radioactivity was measured by quantitative autoradiography. Glucose influx and plasma clearance (permeability times surface area; PS) were calculated from the net disintegrations per minute per gram in brain, the plasma radioactivity integral, and the plasma glucose concentration. In shunted rats influx was decreased by about 22% (in the brain as a whole) compared to that in controls. This decrease was almost entirely due to the decrease in plasma glucose concentrations (27%). The PS, normalized to take plasma concentrations into account, showed a slight decrease in most of the brain except the telencephalon. For the brain as a whole this decrease amounted to 11%. The regional PS and glucose utilization are known to be coupled and the relationship between these was the same in sham-operated and shunted rats. The decrease in PS observed in shunted rats was commensurate with their lower rates of glucose use; thus, the transport process of glucose from plasma to brain appeared to be unaffected by portacaval shunting.

Animals↗
PubMed1986

Regional brain glucose utilization in rats during etomidate anesthesia.

The influence of etomidate on regional cerebral function as reflected by regional cerebral glucose utilization (rCMRGlc) was studied. Three experiments were performed. In the first, rats had both left femoral vessels cannulated and were placed in restraining cages. Etomidate was infused intravenously (12 mg/kg) at a rate of 6 mg X kg-1 X min-1. This large dose had a modest effect on blood pressure and heart rate, which could be explained by the elimination of stress in restrained rats, and no effect on body temperature, Pao2, PaCo2, or pH. A second group of rats were used to determine the effect of etomidate on the ratio of brain glucose to plasma glucose, which is necessary for calculating rCMRGlc. In the third experiment rCMRGlc was measured in unstressed rats. The rats were anesthetized with an intravenous dose of 1, 2, 6, or 12 mg/kg etomidate infused at a rate of 6 mg X kg-1 X min-1. Etomidate had a marked effect on glucose consumption in many, but not all, cerebral structures. The forebrain (telencephalon and diencephalon) was most affected (-25% to -35%) while the hindbrain was minimally affected. There was no demonstrable dose dependency; 1 mg/kg depressed rCMRGlc as much as 12 mg/kg. The pattern of rCMRGlc depression is in accord with the minimal effects observed on physiologic variables and similar to that caused by the steroid anesthetic Althesin, although the depression seen was not as severe. The pattern of metabolic depression produced by etomidate differs markedly from that produced by barbiturates, which affect all brain regions to a similar degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1986

Failure of glucose and branched-chain amino acids to normalize brain glucose use in portacaval shunted rats.

Several abnormalities in brain and plasma amino acid concentrations caused by portacaval shunting in rats return toward normal after 4 days of intravenous infusion with either glucose or glucose with branched-chain amino acids. To assess the effect of such treatment on brain energy metabolism, regional brain glucose use was measured using [14C]glucose and autoradiography, 5 weeks after portacaval shunting. In one experiment intravenous glucose or glucose with branched-chain amino acids was given for 4 days. In a separate experiment the treatment was given orally for 2 weeks, and in addition to glucose use, brain monoamines and amino acids were measured. No other food was provided; the rats had free access to water. Normally fed shunted rats and sham-operated rats served as controls. Both types of oral treatment lowered the high concentrations of tyrosine, phenylalanine, and glutamine in plasma and brain. Glucose without amino acids normalized brain tryptophan. Levels of brain norepinephrine, 5-hydroxytryptamine (serotonin), and 5-hydroxyindoleacetic acid were significantly raised after shunting. Treatment had no effect on norepinephrine but the glucose diet brought the indoles into the normal range. In contrast, neither intravenous nor oral treatment affected brain glucose use, which remained depressed by 25-30% in all brain areas examined.

Amino Acids↗
PubMed1986

Regional ketone body utilization by rat brain in starvation and diabetes.

The rate of ketone body (beta-hydroxybutyrate and acetoacetate) metabolism was measured in individual cerebral structures of fed, starved, and diabetic rats. This was done by infusing beta-[3-14C]hydroxybutyrate intravenously and measuring the incorporation of 14C into brain by quantitative autoradiography. The capacity of the brain to use ketone bodies, expressed as plasma clearance, increased in starvation and diabetes by approximately 50-60%. Plasma clearance was near maximal after 2 days starvation and was not significantly increased after 4 days starvation, 6 days of diabetes or 28 days of diabetes. In all situations the ketone bodies provided only a modest amount of fuel for brain energy metabolism; 3.2% after 2 days starvation and 6.5 and 9.9% after 6 and 28 days of diabetes. The fraction of their energy requirement which the various structures could derive from the ketone bodies differed widely. In general the telencephalon made greatest use of ketone bodies, whereas the hindbrain used least. There was no correlation between the energy requirement of structures (estimated from glucose use in fed rats) and the fraction of energy they could derive from ketone bodies.

3-Hydroxybutyric Acid↗
PubMed1985

Cerebral glucose use measured with [14C]glucose labeled in the 1, 2, or 6 position.

The efficacy of [14C]glucose molecules labeled in various positions as tracers of regional cerebral glucose utilization (rCMRGlc) was examined in rats. Arteriovenous differences of different [14C]-glucose species and 14CO2 were measured across brain to determine the relative rates of 14CO2 loss. As anticipated, 14CO2 evolution decreased in the order: [U-14C]glucose greater than [2-14C]glucose greater than [1-14C]glucose greater than [6-14C]glucose. Release of 14CO2 from [6-14C]glucose was undetectable at 5 min and barely detectable at 10 min, and release from [1-14C]glucose, which includes the pentose phosphate pathway, was only slightly greater. rCMRGlc was measured with [1-14C]-,[2-14C]-, or [6-14C]glucose in 5-min experiments. The results of [1-14C]- and [6-14C]glucose were indistinguishable; no difference due to the activity of the pentose phosphate pathway was found. Both [1-14C]- and [6-14C]-glucose gave values similar to, but on the whole slightly higher than, [2-14C]glucose. It was concluded that when knowledge of total rCMRGlc is required, [6-14C]glucose is the labeled substrate of choice. When the experimental objective is measurement of energy metabolism, use of [1-14C]glucose avoids inclusion of the nonenergy-yielding pentose phosphate pathway.

Animals↗
PubMed1984

Regional cerebral glucose utilization during Althesin anesthesia.

The effect of Althesin, an anesthetic comprising two steroids, on regional cerebral function was determined by measurement of regional cerebral glucose utilization. Rats were anesthetized with an intravenous dose of 4, 8, or 20 mg total steroid/kg. These doses produced anesthesia for 12, 18, and 37 min, respectively. There were no physiologically significant effects of Althesin (20 mg/kg) on body temperature, blood pH, or blood gases. Blood pressure and heart rate decreased slightly after administration of Althesin. Althesin had a profound effect on glucose consumption in many, but not all, cerebral structures. The forebrain (especially cerebral cortex) was affected most, while the hindbrain was much less so or not at all. This pattern of functional depression is in accord with the minimal effects observed on physiologic variables. The effects of Althesin differ from those of other known anesthetics and suggest a unique mechanism. The possibility of action through naturally occurring steroid receptors is considered.

Alfaxalone Alfadolone Mixture↗
PubMed1984

Portacaval anastomosis: brain and plasma metabolite abnormalities and the effect of nutritional therapy.

Rats with portacaval shunts were used as a model of hepatic encephalopathy and compared to shamoperated controls. First, the changes in intermediary metabolites and amino acids in blood and whole brain were characterized and found to be similar at 4 and 7 weeks after shunting. Second, the effects of nutritional therapy on selected metabolites and tryptophan transport into brain were assessed in rats 5 weeks after surgery. Ordinary food was removed and the rats were treated with glucose given either by mouth or intravenously, or intravenous glucose plus branched chain amino acids. Several abnormalities in plasma amino acid concentrations were reversed by treatment. The abnormally high brain uptake index of tryptophan, a consequence of portacaval shunting, was not lowered by any of the treatment regimens; it was even higher in the groups given glucose by mouth and glucose plus amino acids. Calculated competition for entry of tryptophan, phenylalanine, and tyrosine into brain was unchanged (glucose plus amino acids), or reduced (glucose alone). Brain glutamine content was brought to near normal by all treatments. Infusion of glucose plus branched chain amino acids normalized brain content of tryptophan, phenylalanine, and tyrosine, even though the brain uptake index of tryptophan was higher in this group. Thus, partial or complete reversal of several abnormalities found after portacaval shunting was achieved by removal of oral food and administration of glucose. The addition of branched chain amino acids to the glucose infusion restored brain content of three aromatic amino acids to near normal, by a mechanism which appeared to be unrelated to transport across the blood-brain barrier.

Amino Acids↗
PubMed1984

Effect of bedding changes and room ventilation rates on blood and brain ammonia levels in normal rats and rats with portacaval shunts.

Normal rats and rats with portacaval shunts were exposed to low concentrations of atmospheric ammonia generated from decomposing urine and feces. The ammonia concentration in the atmosphere was varied by altering the effective ventilation rate, animal density in the enclosure, and bedding change frequency. Atmospheric ammonia concentrations in the animal holding areas varied inversely with the frequency of bedding change and the rate of air exchange. Significant differences were found between normal and shunted animals in blood ammonia and alkaline phosphatase; brain ammonia, glutamate, and glutamine; and body weight. However, these alterations were the same regardless of the atmospheric ammonia concentration; there were no differences within the control group or shunted group housed in the different conditions. The findings suggest that in the range of ammonia concentrations in this study (0 to 9 ppm), ammonia taken in through the respiratory tract is not accumulated in the body to any significant extent.

Air Pollutants↗
PubMed1983

Regional cerebral glucose utilization in rats with portacaval anastomosis.

Regional cerebral glucose utilization was measured using [2-14C]glucose in rats with an end-to-side portacaval anastomosis. The experiments were conducted in two groups of rats 4 to 8 weeks after portacaval shunting was established. One group was paralyzed and given N2O:O2 (70:30), whereas the other was conscious, unstressed, and unaware of the experiment. In both groups the rate of glucose utilization was decreased in almost all brain structures by an average of 20% after portacaval shunting. The results showed definitively that cerebral energy metabolism was reduced at a time when there were no obvious neurological abnormalities.

Animals↗
PubMed1983

Glucose availability to individual cerebral structures is correlated to glucose metabolism.

Regional cerebral glucose influx was measured using quantitative autoradiography after the intravenous infusion of [2-14C]glucose for a period of 10 or 20 s. Glucose influx varied considerably among structures over an almost threefold range. When compared with rates of regional glucose utilization, a significant correlation by region was found between glucose influx and utilization, demonstrating that the glucose supply to individual cerebral structures is closely matched to their metabolic needs.

Animals↗
PubMed1983

Cerebral glucose utilization in awake unstressed rats.

Regional cerebral glucose utilization (rCMRGlc) was measured in awake unstressed rats by use of [2-14C]glucose autoradiography. Rats prepared by chronic catheterization of the jugular and epigastric veins were placed in specially designed chambers after surgery. The catheters were passed through the top of the chambers. Seven days after surgery, plasma glucose was normal (7.5 mM), plasma ketone bodies were low (0.13 mM), and body weight was maintained. Plasma epinephrine was 31 pg/ml; approximately 3% of the level for stressed (immobilized) rats. Injections and blood sampling through the catheters did not produce changes in heart rate, blood pressure, plasma catecholamines, or blood metabolites. Visual observations did not reveal any signs that the rats were aware of the [2-14C]glucose injections and the subsequent blood sampling. The rCMRGlc in stressed rats was significantly greater than in unstressed rats. This method provides a model for physiological studies in unstressed unanesthetized rats.

Animals↗
PubMed1983

Ammonia selectively stimulates neutral amino acid transport across blood-brain barrier.

The response to increased blood NH4+ of three blood-brain barrier transport systems, which are altered after portacaval anastomosis, was studied. NH4+ acetate was infused for 4 or 22 h to raise blood and brain NH4+, and brain glutamine, to levels similar to those observed after portacaval anastomosis. While brain glutamine content was much higher (16-20 mumol/g) than normal (6 mumol/g) at both times, the permeability of the blood-brain barrier to the neutral amino acid [14C]tryptophan was greater only after 22 h of infusion. After discontinuing the infusion for 5 h, tryptophan transport returned to normal, whereas brain glutamine remained elevated (13 mumol/g). Thus there seemed to be no relationship between the rate of transport and glutamine content. The permeability to [14C]sucrose was unaltered, showing that the integrity of the blood-brain barrier was maintained. Other changes that are characteristic of portacaval shunting, such as decreased basic amino acid ([14C]lysine) and monocarboxylic acid (3-[14C]hydroxybutyrate) transport, were not reproduced by 22 h of infusion. The results demonstrated that the continued presence of NH4+ could be responsible for the change in at least one of the transport systems that are affected by portacaval shunting.

Amino Acids↗
PubMed1983

Regional cerebral glucose utilization measured with [14C]glucose in brief experiments.

A method was developed to measure regional cerebral glucose utilization (rCMRGlc) in very short times using autoradiography and [2- 14C]glucose. It includes a more comprehensive mathematical treatment than prototypes and allows greater experimental flexibility. The current model takes into account the exchange of glucose between plasma and brain as a function of the plasma glucose concentration and rCMRGlc. The loss of 14C as 14CO2, although relatively small, is also calculated and the results corrected accordingly. Fully metabolizable radiolabeled glucose was chosen as the tracer, because it most closely resembles the natural substrate. Glucose is more rapidly phosphorylated than analogues such as 2-deoxyglucose and the 14C accumulated within intermediary metabolites soon account for most of the radioactivity in cerebral tissue. Furthermore, no special constant is necessary to adjust the rates as is the case when analogues are used. Excellent anatomic resolution was achieved when the technique was used to determine rCMRGlc in experiments as short as 5 min. By taking this approach, more short-lived phenomena may be studied under more diverse conditions than was previously possible.

Animals↗
PubMed1982

Regional blood-brain barrier permeability to amino acids after portacaval anastomosis.

The influx of phenylalanine, tryptophan, leucine, and lysine across the blood-brain barrier of individual brain structures was studied in rats 7--8 weeks after a portacaval shunt or sham operation. The method involved a brief infusion of labeled amino acid in tracer quantity and quantitative autoradiography. The clearance rates of phenylalanine, tryptophan, and leucine were increased in proportion to each other in every region examined, but not by the same factor. Tryptophan clearance increased the most (about 200%) and leucine the least (about 30%), compared with phenylalanine (about 80%). This was unexpected, as all three amino acids are believed to be transported by the same mechanism. The changes were most marked in several limbic structures and the reticular formation, whereas the hypothalamus was least affected. Plasma clearance of lysine was decreased in all areas by about 70%. Since the circulating lysine concentration was decreased by 13%, the actual rate of lysine influx was even more reduced. The results demonstrate specific alterations in two different amino acid transport systems. The resulting excess brain neutral amino acids, some of which are neurotransmitter precursors, as well as reduced basic amino acid availability, may be of etiological significance in heptic encephalopathy.

Amino Acids↗