Biomedical subjects

A M Leal

Publications and source records attributed to A M Leal.

17 recordsLinked to original sources

PubMed1999

Ontogenetic diurnal variation of adrenal responsiveness to ACTH and stress in rats.

We performed studies in 8-, 16-, 24-, 30 and 35-day-old Wistar rats at 8.00 h (AM) and 20.00 h (PM) to investigate the relationship between the diurnal variations of basal plasma corticosterone (compound B, CB) and its responses to ACTH and ether stress during the postnatal period. Basal plasma CB levels increased at PM from 8 to 35 days of age and an AM-PM difference was observed at 16 days. Although an AM-PM difference in CB responsiveness to ACTH was detected only at 24 and 35 days, ACTH induced an increasingly higher CB response at PM than at AM from 8 to 35 days. A stress-induced CB response was observed starting at 8 days of age and presented an age-dependent increase; however, no AM-PM difference was observed at any age. The stress-induced CB levels were higher than ACTH-induced CB values at all ages tested except at PM in 8-day old rats. These data demonstrate that the basal CB levels and adrenal sensitivity to ACTH rise during the evening as a function of neonatal development.

Adrenal Glands↗

PubMed1998

Cytoprotective actions of estrogens against tert-butyl hydroperoxide-induced toxicity in hepatocytes.

Estrogens are effective antioxidants in diverse biological systems. Despite their antioxidant activities, it is not known yet whether estrogens prevent or alleviate liver toxicity induced by oxidative stress. In the present work, we studied this possibility by examining in vitro the protective potential of different estrogen compounds (17beta-estradiol, 2-hydroxyestradiol, and diethylstilbestrol) against tert-butyl hydroperoxide-induced hepatocyte damage. Various parameters such as cell viability, lipid peroxidation, adenine nucleotide content, and thiol status were measured as an index of cytotoxicity. The protective effects of estrogens were compared to those of the iron chelator deferoxamine. The molecules tested prevented oxidant-induced cell death differently, showing variable degrees of protection. Deferoxamine was the most potent agent, followed by diethylstilbestrol and 2-hydroxyestradiol, 17beta-estradiol being the least efficient. The inhibitory effects on lipid and thiol oxidations paralleled the effects on cell viability. The molecules also reduced the oxidant-induced ATP depletion, except for 17beta-estradiol which had no effect on the decreased ATP levels. Our results suggest that the mechanisms of the preventive actions of estrogens may be related not only to their antioxidant activity against free radicals, but also and to a lesser extent to the maintenance of the normal redox status of the cell, which partially recovers the intracellular GSH levels.

Adenosine Diphosphate↗

PubMed1997

Daily variation of plasma testosterone, androstenedione, and corticosterone in rats under food restriction.

Food availability is an important synchronizer of the pituitary-adrenal axis and daytime restriction of food access phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, little is known about the synchronizers of circulating androgens in male rats. We studied intact and castrated male rats with free access to food (control groups, C) and with access to food only from 0900 to 1100 hr (food-restricted groups, FR) for 14 days. Blood samples were collected on the 15th day by decapitation at 4-hr intervals. Plasma B concentration in C groups presented diurnal variation with higher values at 2000 than at 0800 hr. In the FR groups there was a 12-hr shift of peak B values. Apparently, castration had no effect on plasma B diurnal variation. In intact rats, plasma testosterone presented similar diurnal variation in both the C and the FR groups. In castrated rats, plasma testosterone was undetectable. Plasma androstenedione similarly varied over time in both C and FR intact rats. However, in castrated animals, the diurnal variation of plasma androstenedione was abolished. Our results indicate that the daily variation of plasma testosterone and androstenedione is dependent on testicular secretion and is not influenced by food availability in the male rat.

Androstenedione↗

PubMed1997

Atrial natriuretic peptide and feeding activity patterns in rats.

This review presents historical data about atrial natriuretic peptide (ANP) from its discovery as an atrial natriuretic factor (ANF) to its role as an atrial natriuretic hormone (ANH). As a hormone, ANP can interact with the hypothalamic-pituitary-adrenal axis (HPA-A) and is related to feeding activity patterns in the rat. Food restriction proved to be an interesting model to investigate this relationship. The role of ANP must be understood within a context of peripheral and central interactions involving different peptides and pathways.

Adrenal Glands↗

PubMed1997

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis.

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.

Animals↗

PubMed1997

Antioxidant action of estrogens in rat hepatocytes.

The in vitro addition of 17 beta-estradiol (0-100 microM) to isolated rat hepatocytes efficiently prevented cellular lipid oxidation induced by the Fe(III)/ADP complex. 17 beta-estradiol was found to be less effective than its metabolic derivative 2-hydroxyestradiol. The presence of specific inhibitors of cytochrome P450 activity significantly diminished the antioxidant capacity of estradiol. These observations support the hypothesis that estradiol, in the micromolar range, inhibits iron-induced lipid peroxidation in liver cells by diverting reducing equivalents from the peroxidative process to its own metabolism.

Animals↗

PubMed1996

Feeding and the diurnal variation of the hypothalamic-pituitary-adrenal axis and its responses to CRH and ACTH in rats.

Daytime restriction of food availability phase-shifts the diurnal periodicity of plasma corticosterone (B) concentration in rats. However, the changes at the various functional levels in the hypothalamic-pituitary-adrenal (HPA) axis are not completely understood. We performed studies in two groups of Wistar rats, a control group with free access to food and a food-restricted group with access to food only from 09.00 to 11.00 h for 14 days. The basal plasma B and ACTH concentrations in the control group presented diurnal variation with higher values in the afternoon than in the morning. In the food-restricted group there was a 12-hour shift of peak B values. Plasma ACTH levels were high in the morning, but there was no significant difference between morning and afternoon values. Plasma AVP presented no diurnal variation in the control group. In the food-restricted group, the diurnal variations of plasma AVP and ACTH-B did not coincide. There was no detectable nycthemeral variation of pituitary ACTH or hypothalamic CRH and AVP contents in either group. Plasma ACTH did not exhibit any diurnal variation in response to CRH in free-fed or food-restricted rats anesthetized with chlorpromazine-morphine-pentobarbital. The administration of ACTH (1-24) resulted in higher B levels in the afternoon in control rats pretreated with dexamethasone once or twice. In the food-restricted group there was a 12-hour shift in the adrenal response to ACTH (1-24). These patterns of response were abolished in both groups when the rats were anesthetized. An in vitro study showed no diurnal variation in adrenal responsiveness to 10(-6) M-10(-9) M ACTH (1-24) stimuli. Our results suggest that anesthesia-related neural or humoral factor(s) other than ACTH are involved in the diurnal periodicity of the HPA axis in free-fed rats and in its shifts in food-restricted rats.

Adrenal Glands↗

PubMed1995

Protective effect of estrogens and catecholestrogens against peroxidative membrane damage in vitro.

The antioxidant effects of natural estrogens (estrone, E1; 17 beta-estradiol), synthetic estrogens (17 alpha-ethynylestradiol, EE2; mestranol, MES; diethylstilbestrol, DES) and catecholestrogens (2-hydroxyestradiol; 4-hydroxyestradiol, 4-OHE2) on lipid peroxidation induced by different means in rat liver microsomes were investigated. The extent of lipid peroxidation was determined by measuring thiobarbituric acid reactive substances. Prooxidants included Fe3+/ADP/reduced NADPH, Fe2+/ascorbate, tert-butyl hydroperoxide (t-BOOH) and 2,2'-azobis(2-amidinopropane) (AAPH). Estrogens and catecholestrogens decreased lipid peroxidation in all four systems tested. In the iron/ascorbate model it was shown that (i) 4-OHE2 and DES had analogous patterns of inhibition, irrespective of the presence of NADPH or the functional integrity of the microsomes, and (ii) the antioxidant activities of E1, EE2 and MES were dependent on the assay conditions with the activity being markedly higher when estrogen metabolism was favored. When peroxidation was initiated by the peroxyl radical generator AAPH, the inhibitory effects observed were least pronounced. Our data also showed that, in each of the systems, all inhibitors displayed the same order of inhibitory potency with DES and catecholestrogens being the most potent antioxidants under all experimental conditions used. The present results confirm earlier findings and point toward a link between estrogen metabolism and estrogen antioxidant activity. The data also indicate that estrogens and catecholestrogens interact with the peroxidative process at different levels with their interactions with iron or the metal-derived species being the most important modes of inhibition.

Animals↗

PubMed1995

Diurnal variation of the pituitary-adrenal and AVP responses to stress in rats under food restriction.

In the present study plasma corticosterone (B), ACTH and vasopressin (AVP) were determined in 2 groups of Wistar rats, a control group (C) with free access to food, and a food restricted group (FR) with access to food only from 0900 to 1100 h for 14 days. Blood samples were collected by decapitation under unstressed (basal) conditions and immediately after 30 minutes of immobilization stress applied at AM (0800 h) and at PM (2000 h). The basal plasma B concentrations in C group presented diurnal variation with higher values at PM than at AM. The restricted feeding regimen resulted in a 12 hour shift of peak B values. Basal plasma ACTH rhythm in group C is parallel to diurnal B variation, attaining higher levels at PM. Rats under food restriction presented higher basal plasma ACTH levels at AM than C group, however there was no AM-PM difference. In both groups after stress plasma B concentrations increased in comparison to those in the unstressed rats. There was no significant AM-PM difference in the absolute B values attained in C or FR groups. The stress-evoked ACTH response was higher at AM than at PM in group C. In the FR group the ACTH response was similar in the morning and evening, although the ACTH concentrations achieved in the morning was lower than in group C. Basal plasma AVP levels were similar at AM and PM in both C and FR groups. Immobilization stress evoked no plasma AVP response in neither groups. Our results indicate that long term food restriction is able to modify the diurnal rhythms of both basal secretion and stress responsiveness of pituitary-adrenal axis by an as yet uncharacterized mechanism.

Adrenocorticotropic Hormone↗

PubMed1994

Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes.

In the present study, the antioxidant effects of estradiol (E2) and 2-hydroxyestradiol (2-OHE2) on microsomal lipid peroxidation induced by Fe3+/ADP/NADPH and Fe2+/ascorbate are described. The extent of lipid peroxidation was measured by thiobarbituric acid reactive substances (TBARS) detection, low-level chemiluminescence, and oxygen consumption. 2-OHE2 had a potent antioxidant activity, which in all cases was higher than that of E2. In the Fe2+/ascorbate model, 2-OHE2 showed a similar pattern of inhibition, irrespective of the presence of NADPH or the functionality of microsomes. However, E2 produced only a slight inhibition when either denatured microsomes or native microsomes without NADPH were used, whereas its protective effect increased considerably when microsomal E2 metabolism was favored. During enzymic Fe3+/ADP/NADPH-induced lipid peroxidation, both E2 and 2-OHE2 were found to provide good protection. Results underline the importance of the chemical structure of these compounds and the role of estradiol metabolism in its antioxidant effects.

Animals↗

PubMed1993

Circadian variations of plasma atrial natriuretic peptide and corticosterone in rats with continuous or restricted access to food.

In the present study plasma Atrial Natriuretic Peptide (ANP) and Corticosterone (B) levels were determined in 2 groups of Wistar rats, a Control group (C) with free access to food, and a Food Shift group (FS) with access to food only from 0900 to 1100 h for 2 weeks. Blood samples were collected by decapitation at 4 hour intervals. ANOVA indicated that B varied over time in both groups (F (6.46) = 10.14, p < 0.0001 for C and F (6.5) = 5.10, p = 0.0005 for FS). There was also time variation in plasma ANP levels in both groups (F (6.54) = 3.78, p = 0.003 for C and F (6.48) = 2.73, p = 0.02 for FS group). Plasma B presented circadian variations from 78 +/- 17 nmol/l (mean +/- SEM) at 0800 h to 339 +/- 79 nmol/l at 2000 h. The day peak plasma ANP level (pmol/l) was also attained at 2000 h (68 +/- 19). This value was higher than all others measured throughout the day. The restricted feeding regimen resulted in a 12 hour shift of peak B values (395 +/- 39 vs 125 +/- 24). The FS rats presented the highest ANP level at 0800 h. The present study indicates similar circadian variations of plasma ANP and B in rats on an ad lib or restricted feeding regimen. ANP and B secretion may occur in anticipation of the feeding period or day activity.

Analysis of Variance↗

PubMed1992

Adrenocorticotropin-corticosterone relationship during dexamethasone therapy in 17 alpha-hydroxylase deficiency.

A previous study in an untreated girl with 17 alpha-hydroxylase deficiency syndrome (17-OHDS) indicated that in the absence of cortisol production, ACTH and corticosterone (B) may interact to modulate the brain-pituitary-adrenocortical system. The ACTH-B interplay was further examined in this patient under dexamethasone therapy and after withdrawal of treatment. Plasma ACTH and B were highly correlated (r = 0.89) during two different schedules of dexamethasone treatment and two weeks off treatment at all blood sampling times (morning, afternoon or 24-h period). A logarithmic-sigmoidal relationship seems to exist between ACTH and B secretion. The time course of ACTH-B relationship early after withdrawal of therapy showed good parallelism between these two variables. Plasma B may be a useful guide for monitoring therapy in 17-OHDS. The present study also indicates the ACTH-B interplay feedback set-points.

Adolescent↗

PubMed1990

Characterization of adrenocorticotropin secretion in a patient with 17 alpha-hydroxylase deficiency.

17 alpha-Hydroxylase deficiency (17-OHDS) is a peculiar type of adrenal insufficiency because of elevated corticosterone (B) production. Episodic and circadian ACTH secretion and the responses to ovine CRH and metyrapone were examined in a female with 17-OHDS under conditions of normal sodium (NSI) and low sodium (LSI) intake. Plasma ACTH and B were higher on LSI than on NSI (mean +/- SD: ACTH, 58 +/- 20 vs. 33 +/- 14 pmol/L; B, 508 +/- 107 vs. 381 +/- 69 nmol/L). ACTH pulses were concomitant with or followed by B pulses. An increase in the amplitude, but not the number, of ACTH and B pulses was found on LSI. Circadian ACTH and B rhythms persisted on LSI. Aldosterone levels were higher on LSI than on NSI. After metyrapone, plasma B decreased in the afternoon (NSI, 220 +/- 10; LSI, 275 +/- 35 nmol/L) and rose on the following morning. Plasma ACTH increased substantially on the following morning (NSI, 135 +/- 47; LSI, 307 +/- 77 pmol/L). The ACTH peak levels after ovine CRH increased after metyrapone administration. These data indicate that B may also have a negative feedback effect at the pituitary level. In all maneuvers, there were no changes in PRA, plasma sodium and potassium, or cortisol. We conclude that in 17-OHDS, in the absence of cortisol production, ACTH and B may interact to modulate the brain-pituitary-adrenocortical system.

Adolescent↗

PubMed1989

The effects of posture changes on blood pressure and heart rate of anesthetized and reserpinized sloths.

1. Tilting sloths anesthetized with chloralose from erect to supine or supine to erect produced little or no effect on heart rate. 2. Tilting anesthetized sloths from erect to supine increased both systolic and diastolic pressures significantly and by about the same amounts. The maximum effect was produced in 20 sec. 3. Pressures stabilized at a higher level than in the erect posture but below the maximum reached in tilting. 4. Tilting these sloths from the supine to the erect posture resulted in a rapid (20 sec) and dramatic fall in pressures to below the initial erect pressure levels. Return to initial erect levels took place slowly. 5. Tilting reserpinized sloths from erect to supine or supine to erect produced little or no effect on heart rate. 6. Tilting reserpinized sloths from erect to supine increased both systolic and diastolic pressures materially and by similar amounts. The maximum effect took 50 sec. 7. Pressures stabilized at higher levels than in the erect posture but less than maximum reached with tilting. 8. Tilting these sloths from supine to erect caused significant falls in pressure to slightly below the initial erect pressure, with maximum effect reached in 30 sec and eventual return to control level. 9. Pressure changes were almost entirely the result of altered venous return. 10. Neither chloralose nor reserpine completely blocked vascular control but reduced it materially.

Anesthesia↗

PubMed1989

Responses of the three-toed sloth, Bradypus tridactylus, to some commonly used pharmacologic agents. II. Chloralose and reserpine.

1. Chloralose, 50 mg/kg i.v., is a safe effective anesthetic for sloths and reduces incidence of cardiac arrhythmias. 2. However, chloralose blocks baroreflexes and may reduce the sensitivity of beta 1 cardiac receptors. 3. Reserpine, 0.70 mg/kg given i.v. in divided doses, blocks the hypertensive effect of 100 micrograms/kg of tyramine in sloths. 4. Reserpine in this dosage materially reduces arterial pressure and heart rate; these effects last at least 7 days. 5. Reserpine potentiates the hypertensive effects of epinephrine and norepinephrine materially. 6. In sloths reserpine increases cardiac irritability but does not block baroreflexes. 7. As is true with most other drugs sloths are more sensitive to chloralose and reserpine than most common laboratory animals.

Animals↗

PubMed1987

Responses of the three-toed sloth, Bradypus tridactylus, to some commonly used pharmacologic agents. I. Autonomic drugs.

1. Sloths are very responsive to epinephrine and norepinephrine; i.v. injection of 1 microgram/kg elevates systolic pressure 80 and 90% respectively. 2. Doses as low as 0.01 microgram/kg of epinephrine as well as norepinephrine raise diastolic pressure. 3. Similarity of effects of these catecholamines can be explained on the basis of the low proportion of skeletal muscle (35 vs 45% in most mammals) and a small liver which reduces the proportion of beta 2 dilators to alpha constrictors responding to epinephrine. 4. Slowness of reflexes allows clear separation of early (0-20 sec), direct accelerating heart rate effect (up 15% with 1 microgram/kg of norepinephrine) and later (20-60 sec), reflex bradycardia (down 30% from control level). 5. Sloths are more sensitive to the vasodilating effects of isoproterenol or less sensitive to beta 1 cardiac stimulating effects than most laboratory mammals; doses as low as 0.1 microgram/kg cause a fall in mean arterial pressure not overcome by increased heart rate.

Animals↗

PubMedDate not supplied

[Urinary lithiasis].

The introduction of extracorporeal shock wave lithotripsy (ESWL) and the development of "minimally invasive" endourological procedures have completely changed the management of urinary calculi. Nevertheless, some aspects in this field still remain controversial. Conservative management is the first option, when the stone can pass spontaneously. The majority of the patients can be successfully treated with ESWL without anaesthesia and in an ambulatory setting or with a 24 H admission. ESWL failures (1 to 2%) and some difficult calculi (cystine calculi, staghorn calculus, stones of great volume and some ureteral stones) can benefit with endourological or percutaneous procedures alone or in association with ESWL. The classical indication for open surgery has changed significantly and surgery is now considered only in some difficult cases and with the failure of minimally invasive procedures. Uric acid calculi, that usually respond to medical treatment, must be treated with alkalinization therapy as the first option.

Humans↗