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Biomedical subjects

M T Nunes

Publications and source records attributed to M T Nunes.

At least 19 recordsLinked to original sources
PubMed2004

Effects of ageing on the energy balance of food-restricted rats.

AIMS: Age can alter energy balance by decreasing the resting metabolic rate. Food restriction can also change energy balance by decreasing energy expenditure as a mechanism of energy conservation. We investigated the influence of food restriction on the energy balance of rats at different ages. METHODS: Wistar EPM-1 female rats were used at ages of 3, 9, 15 and 21 months. At each age, two food intake schedules were provided: control (ad libitum) and food restriction (50%). Animals remained under these schedules for 30 days, and throughout this period body weight, food intake, and stool collection were controlled daily. On the 30th day, animals were killed, blood was collected and the carcasses and faeces were processed for analysis by pump calorimetry. Blood glucose, T(3), T(4) and rT(3) levels were determined. RESULTS: Food restriction reduced energy gain and gross food efficiency of animals at different ages, but more so in older animals. Food-restricted rats also had lower energy expenditure than controls. This reduction was about 40% of the energy expenditure of control animals irrespective of age. Water content increased and fat content decreased in the carcass of food-restricted animals. Serum T(3) and T(4) levels were lower in food-restricted animals pointing out to a major role of thyroid hormones in the mechanism of energy conservation exhibited by food-restricted animals. CONCLUSIONS: The mechanism of energy conservation takes place in all restricted animals and is very important for survival and for species preservation, mainly in aged animals in which food restriction is frequently aggravated by senescence-related organic disorders.

Adipose Tissue↗
PubMed2001

Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat.

Renal glucose reabsorption is mediated by luminal sodium-glucose cotransporters (SGLTs) and basolateral facilitative glucose transporters (GLUTs). The modulators of these transporters are not known, and their substrates glucose and Na+ are potential candidates. In this study we examined the role of glucose and Na+ filtration rate on gene expression of glucose transporters in renal proximal tubule. SGLT1, SGLT2, GLUT1 and GLUT2 mRNAs were assessed by Northern blotting; and GLUT1 and GLUT2 proteins were assessed by Western blotting. Renal cortex and medulla samples from control rats (C), diabetic rats (D) with glycosuria, and insulin-resistant 15-month old rats (I) without glycosuria; and from normal (NS), low (LS), and high (HS) Na+-diet fed rats were studied. Compared to C and I rats, D rats increased (P < 0.05) gene expression of SGLT2 by approximately 36%, SGLT1 by approximately 20%, and GLUT2 by approximately 100%, and reduced (P < 0.05) gene expression of GLUT1 by more than 50%. Compared to NS rats, HS rats increased (P < 0.05) SGLT2, GLUT2, and GLUT1 expression by approximately 100%, with no change in SGLT1 mRNA expression, and LS rats increased (P < 0.05) GLUT1 gene expression by approximately 150%, with no changes in other transporters. In summary, the results showed that changes in glucose or Na+ filtrated rate modulate the glucose transporters gene expression in epithelial cells of the renal proximal tubule.

Animals↗
PubMed2001

Thyroid hormone stimulates myoglobin expression in soleus and extensorum digitalis longus muscles of rats: concomitant alterations in the activities of Krebs cycle oxidative enzymes.

Myoglobin (Mb) gene expression, Citrate Synthase (CS) and Succinate Dehydrogenase (SDH) activities of Soleus (S) and Extensorum Digitalis Longus (EDL) muscles were studied in intact, thyroidectomized and T3-treated (25 microg/100g, BW, ip, 15 days) rats. The fiber type composition of S muscle was also evaluated and used as control of the T3-induced effects. In the S muscle, the T3 treatment increased the Mb mRNA and protein expression, as well as the CS and SDH activity. These changes occurred parallel to the expected increase in type II (fast) and decrease in type I (slow)-fibers in S muscle. In the hypothyroid state, the Mb mRNA was decreased, while the Mb expression and CS activity tended to decrease. In contrast the SDH activity was increased, probably due to the enhanced motor activity that occurs as a short-term response to the hypothermia induced by hypothyroidism. In the EDL, the alterations were milder than those in S muscle in both thyroid states. These findings show that Mb gene expression is induced by T3. This is concomitant with the enhancement of Krebs Cycle enzyme activities and provides additional evidence that thyroid hormone increases the aerobic potential of skeletal muscles, as well as the speed of muscle contraction.

Animals↗
PubMed2001

Functional evidence for the presence of type II 5'-deiodinase in somatotropes and its adaptive role in hypothyroidism.

The anterior pituitary contains abundant type II iodothyronine 5'-deiodinase (D2). The role of this enzyme in mediating thyroid hormone action in the pituitary has been proven only for thyrotropes, although there is evidence that it exists in other cell types, including somatotropes and lactotropes. Here we investigated the potential of D2 to mediate thyroid hormone regulation of growth hormone (GH). Using GH mRNA as an end point, we demonstrate that in hyperthyroid states GH mRNA levels are stimulated by triiodothyronine (T(3)) generated via D1, whereas in hypothyroidism, when D2 activity is markedly increased, GH mRNA is more responsive to tetraiodothyronine (T(4)) in a propylthiouracil-insensitive, reverse T(3)-suppressible manner. Under short-term hyperthyroid conditions, GH levels correlate with plasma T(3); in contrast, the correlation is not observed in hypothyroidism, a condition in which plasma T(3) levels are too low to account for the response. These results add support to the concept that D2 is present in the pituitary and that the enzyme plays an important role in mediating stimulation of GH by thyroid hormones, particularly in hypothyroid states in which they could alleviate the impact of hypothyroxinemia on GH secretion.

Adaptation, Physiological↗
PubMed2001

GLUT4 protein expression in obese and lean 12-month-old rats: insights from different types of data analysis.

GLUT4 protein expression in white adipose tissue (WAT) and skeletal muscle (SM) was investigated in 2-month-old, 12-month-old spontaneously obese or 12-month-old calorie-restricted lean Wistar rats, by considering different parameters of analysis, such as tissue and body weight, and total protein yield of the tissue. In WAT, an approximately 70% decrease was observed in plasma membrane and microsomal GLUT4 protein, expressed as microg protein or g tissue, in both 12-month-old obese and 12-month-old lean rats compared to 2-month-old rats. However, when plasma membrane and microsomal GLUT4 tissue contents were expressed as g body weight, they were the same. In SM, GLUT4 protein content, expressed as microg protein, was similar in 2-month-old and 12-month-old obese rats, whereas it was reduced in 12-month-old obese rats, when expressed as g tissue or g body weight, which may play an important role in insulin resistance. Weight loss did not change the SM GLUT4 content. These results show that altered insulin sensitivity is accompanied by modulation of GLUT4 protein expression. However, the true role of WAT and SM GLUT4 contents in whole-body or tissue insulin sensitivity should be determined considering not only GLUT4 protein expression, but also the strong morphostructural changes in these tissues, which require different types of data analysis.

Adipose Tissue↗
PubMed1996

Facilitatory role of serotonin (5-HT) in the control of thyrotropin releasing hormone/thyrotropin (TRH/TSH) secretion in rats.

In order to investigate the role of serotonin in the regulation of thyrotropin (TSH) secretion, control and propylthiouracil (PTU)-treated male Wistar rats weighing approximately 250 g were subjected to ip injections of methysergide (MET, 10 micrograms/100 g body weight), a serotonergic receptor blocker, and killed 60 min later by decapitation. Serum and pituitary concentrations of TSH were measured by radioimmunoassay. An addition, the pituitary release of TSH was estimated in an in vitro system in which pituitary glands were incubated with hypothalamic extracts. MET treatment led to a decrease in pituitary (94.12 +/- 18.55 vs 199.30 +/- 31.47 micrograms/mg, N = 20), and serum (1.95 +/- 0.92 vs 4.26 +/- 1.40 ng/ml, N = 20) TSH concentration (P < 0.001) and also to a decreased in vitro pituitary response to control hypothalamic extracts (55 +/- 8 vs 78 +/- 7%, N = 5, P < 0.005). In addition, hypothalamic extracts of MET-treated rats significantly facilitated in vitro pituitary TSH secretion, suggesting an enhanced hypothalamic thyrotropin releasing hormone (TRH) activity (347 +/- 62 vs 78 +/- 7%, N = 5, P < 0.001). These results suggest that serotonin participates in the physiological control of TRH/TSH secretion, probably by increasing TRH production/secretion, and/or by facilitating the pituitary TSH response to TRH.

Analysis of Variance↗
PubMed1995

[Neonates born to drug-addicted mothers].

A test was carried out involving 94 newborn babies whose birth occurred in Alfredo da Costa Maternity between November 1991 and February 1994. The aims of this study were to find out the frequency of social and obstetric risks, to assess the neonatal, mobility, namely as regards the withdrawal syndrome, and also the repercussion of drug-addiction in the children's development. The frequency was 1 newborn baby of a drug-addicted mother for 106 pregnant women. In 67 out of 94 cases there was pre-natal follow-up. In such cases, the frequency of prematurity, of the withdrawal syndrome, and the possibility of preventive treatment of sexually contagious illnesses (Syphilis, hepatitis B, and aids) decreased. 8.5% of the 94 newborn babies were handed over to relatives or for adoption. Only in a small number of cases was it possible to keep the babies under regular observation. However, all of them showed hypertony and bulimia, which disappeared between the 8th and 9th months.

Adolescent↗
PubMed1994

Role of thyroid hormone in the control of growth hormone gene expression.

Growth hormone (GH) gene expression was examined in male Wistar rats (200 g) subjected to different manipulations of thyroid status. Thyroidectomy followed by 10 days of treatment with 0.03% methimazole added to drinking water caused a marked decrease in GH mRNA levels estimated by Northern Blot analysis. T3 administration (100 micrograms/100 g body weight, ip, twice daily) to euthyroid rats for one week caused a substantial increase in GH mRNA levels. In another set of experiments, thyroidectomized methimazole-treated rats were killed at different times after a single T3 injection (100 micrograms/100 g body weight, ip). T3 induced a prompt response in GH gene expression by 15 min that reached a maximum after 1 h, remaining so up to 4 h. We conclude that in the rat, GH gene expression is highly dependent on thyroid hormones. Because of the rapidity of the response, the effect is probably mediated by a transcriptional mechanism.

Animals↗
PubMed1992

The role of histamine on the control of thyrotropin secretion in rats.

The presence of histamine (HA) in the hypothalamus, especially in its median eminence, as well as results of previous studies from this laboratory, suggest a participation of this amine in the regulation of TSH (thyroid stimulating hormone, thyrotropin) secretion. In the present investigation, rats were treated with a single injection of cimetidine (CIM - 100 mg/kg ip), an H2-HA receptor antagonist. In vitro release of TSH in response to hypothalamic extracts from control animals, was approximately 20% smaller when evoked from pituitaries obtained from CIM-treated, rather than control animals. The addition of hypothalamic extracts from CIM-treated rats to incubates of pituitaries from either control or CIM treated rats did not significantly change basal TSH secretion, suggesting that TRH (thyrotropin releasing hormone) content was decreased by the anti-histamine treatment. These results point towards a facilitatory role of HA on TSH secretion both at the hypothalamic level where it may interfere with TRH synthesis, as well as at the pituitary level where it may modify TSH response to TRH.

Animals↗
PubMed1989

Hyperthyroid-like metabolic changes induced by chronic administration of compound BW 48/80.

The present study examines the metabolic changes caused by chronic mast cell degranulation in rats. Three groups of 5 adult rats each were used: 1) rats treated with increasing doses of BW 48/80 (2 to 6 mg kg-1 day-1, ip, for 4 days); 2) a control group receiving daily saline injections, and 3) rats treated with disodium chromoglycate (DCG) (40 mg kg-1 day-1,ip, for 4 days). The third group was included as a control since DCG blocks mast cell degranulation. Saline- and DCG-treated rats showed little differences except for an increase in spleen wet weight and liver glycogen content in the latter. Chronic treatment with compound BW 48/80 resulted in statistically significant changes such as body weight loss, reduction in thymus and spleen wet weights, decrease in spleen protein content, liver glycogen and blood insulin concentrations, increase in plasma free fatty acids concentration and adrenal wet weight compared to control rats. These metabolic changes are similar to those reported for hyperthyroidism and support previous findings on the possible role of mast cells in the control of thyroid function.

Animals↗
PubMed1987

The role of glucocorticoids in the stress-induced reduction of extrathyroidal 3,5,3'-triiodothyronine generation in rats.

Serum concentrations of T4, T3, and rT3 as well as liver and kidney 5'-deiodinase activity, have been examined in rats stressed by restraint. After immobilization, serum concentrations of T3 decreased significantly (6 hr, -33 +/- 1%; 8 h, -42 +/- 3%), while serum rT3 increased (6 h, +55 +/- 3%; 8 h, +75 +/- 5%). In the same or similarly treated animals, there was a time-dependent reduction in T4 5'-deiodinase activity in both liver (4 h, -23 +/- 2%; 8 h, -43 +/- 3%) and kidney (4 h, -18 +/- 1%; 8 h, -42 +/- 3%) homogenates. The reduction in hepatic and renal T3 production was due to reduced enzyme activity and not to reduced substrate availability. In spite of reductions in serum TSH (4 h, -9 +/- 1%; 8 h, -51 +/- 5%), the serum T4 concentration did not fall. The serum concentration of corticosterone reached 30 times the basal level after 8 h of restraint. Either adrenalectomy or metyrapone treatment, followed by replacement with nonstress doses of B, completely prevented the alterations of iodothyronine metabolism induced by restraint. These results indicate that the stress-induced elevation of plasma glucocorticoids plays a key role in the pathogenesis of the low T3 syndrome in this model. The reduction in serum T3 may be accounted for by a reduction in T3 production by liver and kidney, adding support to the concept that these organs are an important source of plasma T3 in the rat.

Animals↗
PubMed1986

Extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine in cold-acclimated thyroxine-maintained thyroidectomized rats.

Chronic exposure of rats to cold (4 degrees C) leads to thyroid gland hyperactivity as a compensatory mechanism for activating body heat production. There is increased extrathyroidal production of T3 from T4 in parallel to thyroid hormone hypersecretion. Since the 5'-deiodination (5'-D) of T4 can be modulated by thyroid hormones, it has been suggested that the increased thyroid hormone secretion may activate the 5'-D enzymatic pathway leading to increased extrathyroidal T3 production. In an attempt to explore this possibility, T4 to T3 conversion was studied in liver and kidney homogenates of thyroidectomized rats which received T4 (0.5 to 50 micrograms/100 g body weight per day) for 10 days. Tissue homogenates were incubated with T4 (5 micrograms) for 2 h and the T3 generated was measured by RIA as an index of the activity of the 5'-D pathway. A direct relationship between T4 dose and the production of T3 by the homogenate was observed. 5'-D activity was significantly decreased in hypothyroid rats and greatly increased in hyperthyroid rats. Thyroidectomized rats treated with a replacement dose of T4 (1 microgram/100 g body weight/day) were exposed to 4 degrees C for 60 days. Despite the absence of the thyroid gland, increased 5'-D activity was observed in both liver and kidney homogenates compared to both intact and T4-treated thyroidectomized rats maintained at 25 degrees C. We conclude that chronic cold exposure of rats stimulates 5'-D activity which is independent of the concomitant thyroid gland hyperactivity.

Acclimatization↗
PubMed1985

Conversion of thyroxine (T4) to T3 and rT3 in human leucocyte suspension: its application to clinical investigation.

The generation of T3 and rT3 from added nonradioactive T4 in human polymorphonuclear leucocytes was measured. The amounts of the T3 and rT3 generated were estimated by radioimmunoassay in healthy volunteers and patients suffering of thyroidal and nonthyroidal diseases. Under the incubation conditions employed an increase of in vitro generation of T3 and rT3 was observed in suspensions of hyperthyroid patients, while a significant decrease was found when leucocytes from hypothyroid patients were employed. These alterations were apparently due to either the excess or lack of thyroid hormones, respectively, since they could be restored in both cases by specific clinical treatment. Furthermore, the patients suffering from nonthyroidal illnesses showed decreased T3 generating activity in their leucocyte suspensions, while increased amounts of rT3 could be detected in the same test tube. These results showed that the leucocyte incubation system is a suitable method for investigations of the extrathyroidal metabolism of thyroid hormones in humans.

Adolescent↗
PubMed1983

Influence of mast cells on thyroid function.

The role of mast cells on thyroid gland function was studied with respect to two sites of thyroid control: 1. the thyroid gland; 2. the hypothalamus pituitary system. It was observed that the treatment with disodium cromoglycate (mast cells stabilizer) partially blocked the TSH actions on thyroid gland, thus evidencing the thyroidal mast cells as an intermediary factor of TSH actions on thyroid gland. Furthermore, both T4 and T3 serum concentrations were increased after compound BW48-80 (mast cells disrupter polymer) was administered, concomitantly with increased 1 and 24 h radioiodine uptake, T/S ratio, PB131I and TSH serum concentration. The alterations were not observed in the rats pre-treated with disodium cromoglycate and administered with BW48-80. Finally, BW48-80 promoted an elevation of TSH serum concentration in T4-primed thyroidectomized rats. This phenomenon was completely prevented by the pretreatment with cromoglycate, which confirmed the active participation of mast cells on TRH and/or TSH secretion.

Animals↗
PubMed1981

Possible mechanism of action of cholesterol enriched diet on the thyroid.

Groups of male Sprague Dawley rats aged 60 days were fed either a control diet (CD) or the same diet enriched with 1% cholesterol (CHD) for 30 days. In CHD fed animals an increase of 131I uptake by thyroid, PB131I and TSH level in plasma was found, while the level of thyroxine (T4) was unchanged and that of triiodothyronine (T3) was decreased. In the animals treated with T3 (20 micrograms i.p. daily) a decrease of 131I uptake by thyroid and of T4 and TSH level in plasma was found irrespectively of a cholesterol content in the diet. However, PB131I level was decreased in CHD fed and T3 treated animals compared to those fed CD under the same treatment. Finally, in the animals treated with cimetidine (10 mg i.p. daily) no changes of any measure was found after CD feeding as compared to untreated ones, while CHD in such animals resulted in a decreased of T3 level. The site of cholesterol action appears to be at the hypothalamus-pituitary system since TSH suppressed animals (i.e. T3 treated) did not show any thyroid stimulation when fed with a cholesterol excess. Furthermore, thyroidectomized animals showed increased TSH in plasma after cholesterol feeding. In the present study, chronic administration of cimetidine completely abolished thyroid gland stimulation promoted by cholesterol feeding thus suggesting that central histamine may play a considerable role in this process.

Animals↗
PubMedDate not supplied

Thyroxine induced transformation in sarcoplasmic reticulum of rabbit soleus and psoas muscles.

The properties of the sarcoplasmic reticulum membranes isolated from slow-twitch type I soleus and fast-twitch type II psoas muscles of control and thyroxine treated rabbits were comparatively studied. Membrane yield, maximal calcium storing capacity, ATP-supported calcium uptake, calcium-dependent ATPase activity and calcium-dependent phosphoprotein formation were found to be 3-10 fold higher in psoas than in soleus preparations. Membrane yield, calcium-dependent ATPase activity, ATP-supported calcium transport and calcium-dependent phosphoprotein are at least twice enhanced in the membranes from soleus muscles of animals treated for 14-21 days with thyroxine. The corresponding capacities of the membranes from psoas muscles are not further augmented by the same thyroxine treatment. The maximal calcium storing capacity of the psoas membranes is their sole specific property which is significantly increased. The changes in the properties of the soleus muscles' sarcoplasmic reticulum membranes are engendered by an increase from 5 to 30-50% in the number of type II fibres. Since the calcium transporting properties of the sarcoplasmic reticulum membranes from type II fibres qualitatively differ from those of type I fibres, thyroxine does not only affect quantitative but also qualitative parameters of the muscles' sarcoplasmic reticulum membrane system.

Adenosine Triphosphatases↗