Relative toxicity of two different conditioning regimens in patients undergoing allogeneic bone marrow transplantation.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
A Machado
Publications and source records attributed to A Machado.
Effects of enucleation on postnatal development of catecholamines and serotonin metabolism in the superior colliculus of the rat.
We have measured the level of catecholamines and serotonin and their principal metabolites, and the activities of tyrosine hydroxylase, tryptophan hydroxylase and monoamine oxidase-A and -B in the rat superior colliculus during postnatal development after bilateral removal of the eyes. The visual deprivation has different effects on the catecholamines and serotonin metabolism. The major changes in both amines were at day 15. Tyrosine hydroxylase and tryptophan hydroxylase activities increased during postnatal development but this increase was higher in enucleated compared with controls. An increase of the MAO-B to MAO-A ratio during postnatal development was found. The significance of these changes has been discussed.
Aging↗
Possible involvement of NADPH requirement in regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenase levels in rat liver.
Previous studies examining regulation of synthesis of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase in rat liver have focussed on the induction of these enzymes by different diets and some hormones. However, the precise mechanism regulating increases in the activities of these enzymes is unknown and the factors involved remain unidentified. Considering that many of these metabolic conditions occur simultaneously with the increase of some NADPH consuming pathway, in particular fatty acid synthesis, we suggest that the activities of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase could be regulated through a mechanism involving changes in the NADPH requirement. Here, we have studied the effect of changes in the flux through different NADPH consuming pathways on the NADPH/NADP ratio and on Glucose-6-Phosphate and 6-Phosphogluconate levels. The results show that: i) an increase in consumption of NADPH, caused by activation of fatty acid synthesis or the detoxification system which consumes NADPH, is paralleled by an increase in levels of these enzymes; ii) when increase in consumption of NADPH is prevented, Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase levels do not change.
Animals↗
Determination of levels of biogenic amines and their metabolites and both forms of monoamine oxidase in prefrontal cortex of aged rats.
Levels of dopamine, noradrenaline and serotonin and their metabolites and the activities of monoamine oxidase A and B, have been determined in the prefrontal cortex of the rat during ageing. Serotonin turnover rate has been measured as 5-hydroxytryptophan accumulation rate after central decarboxylase inhibition. The major changes were an increase of dopamine and noradrenaline levels and a decrease of serotonin in aged animals compared with control animals. A decrease of the MAO-A to MAO-B ratio was found in aged rats.
Aging↗
Desipramine blocks stress-induced prolactin release in rats: role of central beta-2 adrenoceptors.
1. The present study was designed to examine the relationship between beta-adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. 2. Chronic administration of desipramine (15 mg kg-1 day-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. 3. Intracerebroventricular administration of the beta-2 adrenoceptor agonist salbutamol (1 microgram/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. 4. We conclude that beta-2 adrenoceptors play a role in the control of prolactin release in response to stress.
Albuterol↗
Implication of lysine residues in the loss of enzymatic activity in rat liver 6-phosphogluconate dehydrogenase found in aging.
During aging, there is a decrease in the activity of the 6-phosphogluconate dehydrogenase enzyme in rat liver. The "old" 6-phosphogluconate dehydrogenase enzyme is about 26% less active than the "young" enzyme. In this paper, some biochemical and chemical properties of this enzyme are studied. 2,4,6-Trinitro-benzenesulfonic acid measurements indicate that the old enzyme has 11 lysine residues less than the young enzyme. The proteolysis with trypsin produces more peptides in the young enzyme than in the old one. However, similar numbers of peptides were produced when endoproteinase Arg-C was used on both enzymes. Moreover, the treatment of the young enzyme with ascorbate for 15 min produces the loss of 8 lysine residues. These results suggest that during aging there is a modification of the lysine residue, and this could be involved in the loss of its enzymatic activity.
Aging↗
Inhibition of fatty acid biosynthesis by bezafibrate in different rat cells.
Bezafibrate is one of the main drugs used in the treatment of human hyperlipemic diseases. Its action on the biosynthesis of fatty acids has been studied and the following conclusions have been drawn: (1) Lipogenesis from glucose is inhibited in hepatocytes and adipocytes isolated from "refed" rats previously treated with bezafibrate. (2) Lipogenesis from glucose is inhibited by bezafibrate in hepatocytes and adipocytes isolated from "refed" rats. (3) Lipogenesis from glucose is also inhibited by bezafibrate in acini isolated from lactating rats. These results show that bezafibrate is an inhibitor of fatty acid synthesis.
Adipose Tissue↗
Determination of monoamines and both forms of monoamine oxidase in the rat's substantia nigra during postnatal development.
Changes in biogenic amine content in the substantia nigra and in both forms of monoamine oxidase in substantia nigra and striatum of the rat during postnatal development (15-180 days) have been studied. Dopamine and serotonin had the same levels at day 15, however, each monoamine showed a different developmental profile. Dopamine levels and their metabolites (except 3-methoxytyramine) decreased during postnatal development. Serotonin levels and their main metabolite, 5-hydroxyindolacetic acid, underwent an increase during all stages studied. There were no statistically significant changes in noradrenaline levels until day 180 when they increased with respect to day 15. The highest activity of the monoamine oxidase-A in substantia nigra coincided with the highest 5-hydroxyindolacetic acid:serotonin ratio. Monoamine oxidase-A in the striatum did not change contrary to that which happened in substantia nigra. The monoamine oxidase-B:monoamine oxidase-A ratio increased during development both in the substantia nigra and the striatum. The significance of these changes is discussed.
Aging↗
Age-related changes of catecholamines and their metabolites content in the visual system of the rat.
The changes in the content of the catecholamines in each structure of the geniculate and extrageniculate visual system of the rat during the aging period (6-30 months) have been studied. Dopamine was found at lower levels than noradrenaline in all the structures. The dopamine and noradrenaline showed different developmental profiles. Dopamine and its metabolite levels decreased in the lateral geniculate and visual cortex and increased in superior colliculus and posterior thalamus. Noradrenaline and its metabolites increased in all structures during the aging period. However, 3-methoxy-4-hydroxyphenylglycol/noradrenaline and normetanephrine/noradrenaline ratios decreased in all structures except in superior colliculus. These results suggest age-related changes in the catecholamines in the visual system of the rat.
3,4-Dihydroxyphenylacetic Acid↗
Changes in monoamines and their metabolite levels in substantia nigra of aged rats.
A decrease in the monoamine and monoamine metabolite contents in the substantia nigra of aged rats vs. controls has been found. Hence, it can be speculated that this decrease may play a role in the multiple alterations in dopaminergic functions observed in aged rats.
Age Factors↗
Operant conditioning of behavioral variability using a percentile reinforcement schedule.
The present investigation developed and tested a new percentile reinforcement schedule suited to study pattern variability, whose main feature was the relative dissociation it provided between the variability requirement defining criterional responses and overall probability of reinforcement. In a discrete-trials procedure, pigeons produced patterns of four pecks on two response keys. If the pattern emitted on the current trial differed from the N preceding patterns, reinforcement was delivered with probability mu. The schedule continuously adjusted the criterion N such that the probability of a criterional response, estimated from the subject's recent behavior, was always constant. In these circumstances, the criterion corresponded to an invariant percentile in the distribution of recent responses. Using a between-subjects design, Experiment 1 manipulated the variability requirement--the percentile--while keeping overall reinforcement probability constant. The degree of variability varied directly with the requirement. In addition, an inverse relationship existed between the requirement and within-group variance. Experiment 2 manipulated probability of reinforcement while maintaining the variability requirement constant. No consistent relationship was found between variability and reinforcement probability. A tentative hypothesis was advanced ascribing the operant conditioning of behavioral variability to a process of probability-dependent selection.
Animals↗
Possible involvement of histidine residues in the loss of enzymatic activity of rat liver malic enzyme during aging.
During aging there is a decrease in activity of the malic enzyme in rat liver. The "old" malic enzyme is about 36% less active than the "young" enzyme. Some properties and modifications of amino acid residues are studied here (--SH, arginine, methionine, histidine, lysine) to try and check on the existence of any relationship between them and the loss of enzymatic activity during aging. Diethyl pyrocarbonate measurements indicate that the old enzyme has 1 histidine residue less than the young enzyme. Moreover, the treatment of the young enzyme with ascorbate for 15 min produces the loss of 36% of the enzymatic activity and the loss of 1.2 histidine residues. These results suggest that during aging the modification of the histidine residue could be involved in the loss of its enzymatic activity.
Aging↗
Changes in biogenic amines in rat hippocampus during development and aging.
The effects of postnatal development and aging on the concentration of dopamine, noradrenaline, serotonin and their principle metabolites have been studied in the hippocampus of the rat. During development the concentration of dopamine increases 1.5 fold during the first 90 days. 3-methoxytyramine was found in low concentrations. The homovanillic acid and DOPAC concentrations showed no changes apart from a decrease at day 15 and an increase at day 8, respectively. From birth up to 30 months, the noradrenaline concentration increased by a factor of about 10. Their metabolites each showed a different profile. The concentration of tryptophan was always the highest among the compounds studied. It decreased from birth to day 15, while the concentration of serotonin and 5-hydroxyindolacetic acid increased 3 and 5 fold respectively during this time. However, 5-hydroxytryptophan and 5-hydroxytryptophol concentrations were very low and unchanged at all stages. These findings led to the conclusion that the neurotransmitters: noradrenaline and serotonin, are developed in the hippocampus during the first three months. During aging, the serotonin concentration is increased without significant change in the other compounds studied.
3,4-Dihydroxyphenylacetic Acid↗
Changes in some hepatic enzyme activities related to phase II drug metabolism in male and female rats as a function of age.
Changes in activity of some hepatic enzymes related to UDP-glucuronic acid conjugation (UDP-glucose dehydrogenase and UDP-glucuronyl transferase) and glutathione-related enzymes (glutathione reductase and glutathione peroxidase) were investigated in male and female Wistar rats as a function of age. UDP-glucose dehydrogenase activity showed a decrease in the ageing period in both sexes (26.4% and 37.7% in males and females respectively), and no sex differences were found in all the ages studied. The UDP-glucuronyl transferase (using p-nitrophenol as substrate) showed an age-dependent decrease in its activity for males, but an increase for female rats. A sex difference (male values were higher than female values) was observed only in young rats (1 and 3 months old). Glutathione peroxidase activity increased with age in both sexes (the activity found in male and female old rats was about 162% and 149% respectively to those found in adulthood), and a marked difference was observed between sexes in young and old rats (57.8% and 45.4% higher in females in young and old rats respectively). In contrast, the glutathione reductase activity showed a decrease in the ageing (39% in male and 35.5% in female) and the highest levels during lifetime was found in males.
Aging↗
Short-term control of the pentose phosphate cycle by insulin could be modulated by the NADPH/NADP ratio in rat adipocytes and hepatocytes.
The short-term activation of the pentose phosphate cycle by insulin in rat adipocytes and hepatocytes has been studied. This NADPH-producing pathway is regulated by the activation or inhibition of different NADPH-consuming pathways. The stimulation of the fatty acid synthesis by insulin produced an increase in the flux through the pentose phosphate cycle. Kynurenate produced a decrease in the fatty acid synthesis and, consequently a diminution in the flux through the pentose phosphate cycle. Incubation of adipocytes and hepatocytes in presence of kynurenate (10 mM and 3 mM respectively) and insulin (5 nM), prevents both insulin activation on fatty acid synthesis and pentose phosphate cycle. These results suggest that insulin activates the pentose phosphate cycle through the activation of fatty acid synthesis.
Adipose Tissue↗
The NADPH consumption regulates the NADPH-producing pathways (pentose phosphate cycle and malic enzyme) in rat adipocytes.
The changes in the activity of the pentose phosphate cycle and the malic enzyme produced by the activation or inhibition of different NADPH-consuming pathways have been studied. The inhibition of the fatty acid synthesis by kynurenate produced a decrease in the flux through the pentose phosphate cycle and a diminution in the malic enzyme pathway. The incubation of the adipocytes in the presence of ter-butyl-hydroperoxide, a compound which is metabolized via a NADPH-consuming pathway, produced a big increase in the pentose phosphate cycle and the malic enzyme activities. The regulation of these NADPH-producing pathways by the NADPH/NADP ratio is discussed.
Adipose Tissue↗
Age-related changes of serotonin and its metabolites content in the visual system of the rat.
Measurements have been taken of the serotonin and its metabolites (tryptophan, 5-hydroxytryptophan, 5-hydroxy-3-indolacetic acid and 5-hydroxytryptophol) in each structure of the geniculate and extrageniculate visual system of rats aged between 3 and 30 months. The concentration of tryptophan was the highest of all compounds studied. Its increase during ageing is statistically significant in the lateral geniculate and posterior thalamus. 5-HTP concentration was very low and in some cases not detectable. 5-HT concentrations and its principal metabolite, 5-HIAA, showed a different profile in each brain structure. The lateral geniculate and visual cortex showed statistically significant changes, but with opposite results. In the lateral geniculate the 5-HT and 5-HIAA concentrations were increased during the ageing period. However, in the visual cortex the 5-HT and 5-HIAA concentrations decreased in the same period. These age-related changes were not seen in the superior colliculus and posterior thalamus as in the 5-HT levels as in the 5-HIAA. 5-hydroxytryptophol was always found in low concentration. These results suggest age-related changes in the geniculate visual system.
Aging↗
Variations due to hyperoxia and ageing in the activities of glutathione S-transferase and NADPH-cytochrome c reductase.
We have studied the influence of hyperoxia and ageing on the activities of NADPH-cytochrome c reductase and glutathione S-transferase in different rat organs. Lung glutathione S-transferase activity increases markedly in 5-day-old pups exposed to hyperoxia, as observed for the O2- scavenging enzyme, superoxide dismutase. The levels of NADPH-cytochrome c reductase increase as well but after a 3-day lag period. In the liver, there is a pronounced decrease of both activities in 24-month-old rats, but at 12 months the activity of glutathione S-transferase increases whereas that of NADPH cytochrome c reductase activity decreases with respect to 3 months. The pattern of variations with age of NADPH cytochrome c reductase is similar in liver and brain. However the behaviour of brain glutathione S-transferase parallels that of the liver enzyme only up to 12 months. Thereafter the brain activity is maintained at a high level. These observations open the possibility that the high glutathione S-transferase levels in the old rat brain might be involved in protection towards oxidative alterations during ageing.
Aging↗