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Biomedical subjects

A Machado

Publications and source records attributed to A Machado.

At least 163 records · Page 9Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Measurement ex-vivo of the inhibition of fatty acid biosynthesis by bezafibrate administration in different rat tissues.

The action of bezafibrate on fatty acid biosynthesis pathways has been examined in rat tissues. The drug abolished the induction of fatty acid synthesis that occurs on refeeding the animals with a high carbohydrate diet and by insulin administration in liver and adipose tissue. The rates of fatty acid biosynthesis in these tissues were estimated from the incorporation of 3H into lipids from 3H2O.

Adipose Tissue↗
PubMed1987

The NADPH-producing pathways (pentose phosphate and malic enzyme) are regulated by the NADPH consumption in rat mammary gland.

We have studied 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. Kynurenate, an acetyl-CoA-carboxylase inhibitor produced a decrease in the flux through the NADPH-producing pathways pentose phosphate cycle and malic enzyme. Acini (isolated from mammary gland) incubated in the presence of ter-butyl-hydroperoxide, a compound which is metabolized via a NADPH-consuming pathway, showed a substantial increase in the pentose phosphate cycle and the malic enzyme pathways.

Animals↗
PubMed1986

Malic enzyme levels are increased by the activation of NADPH-consuming pathways: detoxification processes.

The administration to rats of either t-butyl hydroperoxide or phenobarbital, compounds that are metabolized through detoxification processes, produces an increase in specific activity of the NADPH-consuming enzymes, glutathione reductase and NADPH-cytochrome c reductase. These compounds also produce a very significant increase in the specific activity of malic enzyme. Immunoprecipitation with a specific antibody for malic enzyme indicates that specific activity changes are the result of corresponding changes in the amounts of enzyme protein present. The administration of 1,3-bis(chloroethyl(-1-nitrosourea (a glutathione reductase inhibitor) together with t-butyl hydroperoxide abolishes any stimulation of malic enzyme activity. These results indicate that an increase in NADPH consumption induces the synthesis of malic enzyme. Alternatively, a protection of enzyme degradation cannot be rigorously excluded.

Adipose Tissue↗
PubMed1986

Increased basal gluconeogenesis in the aged rat.

Post-absorptive gluconeogenesis from lactate measured in vivo increases 3-fold in 24-month-old rats compared to 3-month-old animals. Fractional lactate turnover rates showed no significant differences between the two groups of animals. Lower plasma glucose concentrations and insulin-glucagon ratios may explain the increase in gluconeogenesis observed in aged rats.

Aging↗
PubMed1986

Morphological changes in the retina of ageing rats.

This paper deals with the morphological changes in the retina with ageing. The most significant result was a decrease in the thickness of the aged retina compared to that of the controls. Although all layers underwent reduction, the most affected were the outer nuclear layer (that was reduced to 90%) and the ganglion cell number (which was reduced to 40%). The surviving photoreceptors and ganglion cells showed structural changes. In the photoreceptors we found a disappearance of the outer segments, and in many instances the inner segment was in direct contact with microvilli from the pigment epithelium. In the ganglion cells we found an increase in Golgi apparatus, however, not at a uniform rate but to different degrees in the different cells.

Aging↗
PubMed1986

Age and sex related differences in some rat renal NADPH-consuming detoxification enzymes.

Age- and sex-associated changes in some renal drug-metabolizing enzyme activities (NADPH-cytochrome c reductase, the glutathione peroxidase-glutathione reductase system, and thioredoxin reductase) were investigated using male and female Wistar rats (ages ranging from -4 days to 24 months). During aging the activities of NADPH-cytochrome c reductase and thioredoxin reductase showed a marked decrease (approximately 50% in both enzymes compared to adult stage). Glutathione reductase activity presented similar values in adulthood and aging, and glutathione peroxidase activity showed an increase with age (30% compared with the adult values). A marked sex difference was observed in young rats for glutathione peroxidase and thioredoxin reductase activities. However, during aging this difference disappears for glutathione peroxidase activity, but it remains for thioredoxin reductase activity (the specific activity in male old rats was approximately two-fold that obtained from female old rats). The variations in these enzymatic activities may be important when determining the changes in susceptibility of the kidneys to toxic chemicals with aging.

Aging↗
PubMed1986

The change with age in biogenic amines and their metabolites in the striatum of the rat.

The changes in the content of the biogenic amines and their metabolites in the striatum of the rat during the aging period (3-30 months) have been studied. The maximum levels of dopamine (DA) have been found at 6 months of age and this concentration is maintained until 24 months. Between 24 to 30 months there is a decrease in the concentration of this compound. At that time, there is a slight increase in 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) concentration, the main metabolites of DA, which suggests a slight increase in DA metabolism. The 3-methoxytyramine (3-MT) concentration also increases at this time. The maximum concentration of noradrenaline (NA) was also found at 6 months of age. Tryptophan has the maximum concentration after DA and this is maintained over the life-span of the rat. The concentration of serotonin (5-HT) is high and does not change during this period. However, the concentration of 5-HT, as occurred with DA, decreased between 24 and 30 months. Also the DA/5-HT ratio does not change during the period studied.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

The pentose phosphate cycle is regulated by NADPH/NADP ratio in rat liver.

The changes in the activity of the pentose phosphate cycle produced by the activation or inhibition of different NADPH-consuming pathways have been studied. The inhibition of fatty acid synthesis by kynurenate produced to the same extent, inhibition of the pentose phosphate cycle activity and an increase (about twofold) in the NADPH/NADP ratio. The addition of ter-butyl-hydroperoxide or paraquat, which is metabolized via NADPH-consuming pathways, produced the activation of the pentose phosphate cycle and a decrease in the NADPH/NADP ratio (about threefold). The plot of the NADPH/NADP ratio versus the pentose phosphate cycle activity gave a straight line with a regression index of 0.999. The regulation of the pentose phosphate cycle mainly by the intracellular NADPH/NADP ratio is discussed.

Animals↗
PubMed1985

Impairment of glutamate uptake and absence of alterations in the energy-transducing ability of old rat brain mitochondria.

The proton electrochemical gradient has been measured in old brain mitochondria isolated from 2- or 24-month-old rats with the use of different respiratory substrates. With succinate as substrate, neither the respiratory rate, membrane potential or delta pH varied with age, indicating that the dielectric strength of the mitochondrial membrane was unaltered in old animals. The ohmic behavior of the membrane was tested in experiments in which the respiratory rate was partially inhibited by malonate, and was found to be unchanged with age. When glutamate plus malate were used as substrates, the respiratory rate was substantially reduced, and a drastic decrease in glutamate uptake was observed in old rat brain mitochondria.

Aging↗
PubMed1985

Age-dependent modifications of rat heart succinate dehydrogenase.

The activity of rat heart succinate dehydrogenase (SDH) increases 1.7-fold in old animals (Vitorica, J., Cano, J., Satrústegui, J. and Machado, A., Mech. Ageing Dev., 16 (1981) 105-116). This increase is due to an increase in enzyme protein itself because: (a) the activation state of the enzyme does not vary with age; and (b) the increase of activity is paralleled by an increase in immunoprecipitable SDH in old rat heart mitochondria. SDH from old rat heart mitochondria differs in a number of ways from that of young animals: (a) The km value for succinate increases with age. (b) The thermostability decreases, and the activation energy in the 20-40 degrees C interval is higher in old animals. (c) The breaking points of the Arrhenius plots of SDH are shifted to higher values. (d) Reactivity towards N-ethylmaleimide in succinate protected mitochondria decreases with age.

Aging↗
PubMed1985

Regulation by ammonium of glutamate dehydrogenase (NADP+) from Saccharomyces cerevisiae.

The activity of glutamate dehydrogenase (NADP+) (EC 1.4.1.4; NADP-GDH) of Saccharomyces cerevisiae is decreased under conditions in which intracellular ammonia concentrations increases. A high internal ammonia concentration can be obtained (a) by increasing the ammonium sulphate concentration in the culture medium, and (b) by growing the yeast either in acetate + ammonia media, where the pH of the medium rises during growth, or in heavily buffered glucose + ammonia media at pH 7.5. Under these conditions cellular oxoglutarate concentrations do not vary and changes in NADP-GDH activity appear to provide a constant rate of oxoglutarate utilization. The following results suggest that the decrease in NADP-GDH activity in ammonia-accumulating yeast cells is brought about by repression of synthesis: (i) after a shift to high ammonium sulphate concentrations, the number of units of activity per cell decreased as the inverse of cell doubling; and (ii) the rate of degradation of labelled NADP-GDH was essentially the same in ammonia-accumulating yeast cells and in controls, whereas the synthesis constant was much lower in the ammonia-accumulating cells than in the controls.

Acetates↗