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Biomedical subjects

F Brandão

Publications and source records attributed to F Brandão.

At least 19 recordsLinked to original sources
PubMed2000

Synaptic reorganization in the hippocampal formation of alcohol-fed rats may compensate for functional deficits related to neuronal loss.

We have examined the behavioral and neuroanatomical effects of long-term alcohol intake in rats ingesting a 20% solution of ethanol for 30 weeks. Previous studies have shown that this treatment provokes neuronal degeneration in the hippocampal formation, which occurs in parallel with remodeling processes. Spatial reference and working memory of alcohol-fed rats were evaluated during last 4 weeks of treatment by comparison of their performance with age-matched controls on the Morris water maze. Alcohol consumption did not affect the performance of rats in the reference memory task as indicated by the measures derived from the acquisition trials and from the probe-trial, which were highly similar for alcohol-fed and control animals. Also, performance in the working memory task was not significantly altered in alcohol-treated animals. No treatment-related changes in swim speed or impairments of sensorimotor abilities, tested in the visible platform task, were detected. Stereological methods were applied to evaluate the damage inflicted by alcohol intake in the structure of the hippocampal formation. In the alcohol-treated animals, there was a noticeable cell loss in the granular layer of the dentate gyrus (10%), and in CA3 (18%) and CA1 (19%) hippocampal subdivisions. In spite of the neuronal loss, the total number of synapses between mossy fibers and CA3 pyramids was unaffected by alcohol treatment suggesting that new synaptic contacts were formed between the surviving neurons. We show that, regardless the marked hippocampal cell loss in rats exposed to chronic alcohol intake, the reorganization that takes place at the synaptic level may alleviate the expected functional deficits.

Alcohol Drinking↗
PubMed1999

Brain natriuretic peptide as a marker of cardiac involvement in hypertension.

Hypertensive patients with heart abnormalities have increased risk of cardiovascular events. Brain natriuretic peptide is a natriuretic peptide mainly of ventricular origin produced in response to pressure and stretch. We hypothesise that brain natriuretic peptide could be a useful marker of cardiac remodelling in hypertensive patients. We studied 36 consecutive community mild-to-moderate hypertensive patients and 11 well-matched normotensive controls with respect to clinical characteristics, brain natriuretic peptide, creatinine and echocardiography parameters (M-mode, 2-D arid transmitral pulsed Doppler). Brain natriuretic peptide levels were significantly higher in hypertensive patients than in controls [36.54 (IQR: 38.61) vs. 10.30 (IQR: 13.20) pg ml(-1), p<0.0001] and it was correlated with left ventricular mass index. Hypertensive patients with impairment of diastolic filling had significantly higher brain natriuretic peptide concentrations than patients with no abnormalities on echocardiography [61.16 (45.38) vs. 31.27 (18.10) pg ml(-1), p=0.001]. Multivariate analysis showed that only diastolic dysfunction and left ventricular mass index were significantly and independently related with brain natriuretic peptide concentrations in this population. In conclusion, impairment of diastolic function and left ventricular mass index are related to brain natriuretic peptide levels, thus giving the insight that this peptide can be a marker of ventricular remodelling in hypertensive patients.

Aged↗
PubMed1999

GM1 and piracetam do not revert the alcohol-induced depletion of cholinergic fibers in the hippocampal formation of the rat.

Chronic alcohol consumption causes a depletion of the cholinergic fiber network in the rat hippocampal formation, which is not ameliorated by alcohol withdrawal. Following withdrawal from alcohol, there is a further loss of intrinsic hippocampal cholinergic neurons. In this study, we investigated whether treatment with putative neuroprotective agents during the entire withdrawal period would have beneficial effects upon the hippocampal cholinergic innervation. Adult male rats were alcohol-fed for 6 months and subsequently withdrawn from alcohol for 6 months. Some animals were treated with either ganglioside GM1 (35 mg/kg body weight s.c.), vehicle (saline s.c.), or piracetam (800 mg/kg body weight p.o.) for the entire withdrawal period. Choline acetyltransferase (ChAT) immunoreactive (IR) fibers and neurons were analyzed quantitatively in all four animal groups. There were no significant differences in the density of the ChAT-IR hippocampal fiber network when the pure withdrawal and withdrawal + vehicle groups were compared to the withdrawal + GM1 or withdrawal + piracetam groups. In contrast, the number of ChAT-IR interneurons in the hippocampal formation was higher in the withdrawal + GM1 or withdrawal + piracetam groups than in the pure withdrawal and withdrawal + vehicle groups. These results indicate that, in the doses used, neither neuroprotective agent had an effect upon the extrinsic cholinergic innervation, but they had a beneficial effect upon the hippocampal intrinsic cholinergic system.

Animals↗
PubMed1997

Intracerebral grafts promote recovery of the cholinergic innervation of the hippocampal formation in rats withdrawn from chronic alcohol intake. An immunocytochemical study.

We have previously found that alcohol withdrawal aggravates the neuronal cell loss induced by chronic alcohol consumption in the rat hippocampal formation. We have also shown that intracerebral grafts of immature hippocampal tissue could reverse the progressive degeneration that occurs during this withdrawal. Furthermore, we have shown that chronic alcohol consumption reduces the areal density of choline acetyltransferase-immunoreactive neurons and the density of choline acetyltransferase-immunoreactive fibres in the hippocampal formation. Thus, we thought it would be of interest to investigate the effects of alcohol withdrawal in the hippocampal cholinergic innervation and to determine whether the intracerebral grafting of immature hippocampal tissue would have beneficial effects upon the cholinergic system in this condition. Choline acetyltransferase-immunoreactive fibres and perikarya were analysed in 14-month-old control, alcohol-fed, withdrawal and withdrawal-grafted groups of rats. The areal density of choline acetyltransferase-immunoreactive neurons was reduced in all experimental groups when compared to controls. The density of choline acetyltransferase-immunoreactive fibres was lower in the alcohol-fed and withdrawal groups than in the control and withdrawal-grafted groups. We conclude that the grafted tissue probably produced neurotrophic factors which allowed a recovery of the hippocampal cholinergic fibre network. This recovery might be of importance to reverse the cognitive dysfunction described after chronic alcohol consumption and withdrawal.

Animals↗
PubMed1996

Homogeneous or heterogeneous distribution of systemically administered adrenaline: organ dependence.

In incubation experiments it was shown that exogenous adrenaline or noradrenaline does not distribute homogeneously into the adrenergic varicosities of the rat vas deferens (wall with thick and compact muscle layer) but does distribute homogeneously in the rat spleen capsule (thin and loose muscle layer, containing more extracellular space than the vas deferens). To circumvent any hypothetical role of the muscular layer in the distribution of the amine, 100 micrograms.kg-1.h-1 adrenaline was administered to rats in vivo either i.v. (during 90 min) or i.p. (under pentobarbital anaesthesia, an Alzet minipump was implanted which delivered that dose during 6 days). The rats also received 100 mg.kg-1 pargyline (to inhibit MAO) and 100 mg.kg-1 tropolone (to inhibit COMT). At the end of adrenaline administration, vasa deferentia and spleen capsule were removed, washed and then exposed to 100 mumol.l-1 tyramine for 20 min. At the end of this exposure, the ratio noradrenaline/adrenaline in the tissue and in the medium was compared. In the vas deferens both after i.v. and i.p. administration of adrenaline, the ratio noradrenaline/adrenaline was about 3 times higher in the medium than in the tissue, while in the spleen capsule the ratio noradrenaline/adrenaline was not significantly different in the medium and in the tissue. We conclude that, even when the amine reaches the storage sites from the blood, it distributes homogeneously in the spleen capsule and heterogeneously in the vas deferens, perhaps because there are more than one kind of storage vesicles in the vas deferens.

Adrenergic Agents↗
PubMed1996

Lisinopril and diltiazem reduce left ventricular mass without changing blood pressure in normotensive subjects with exaggerated blood pressure response to exercise.

OBJECTIVE: To determine whether high left ventricular mass may be reduced by antihypertensive drugs in normotensives with exaggerated blood pressure response to exercise as it occurs in hypertensive patients. DESIGN AND METHODS: Randomized, single blind, controlled parallel study evaluating the influence of placebo; lisinopril 20 mg/day, diltiazem 180 mg/d for 5-6 months on left ventricular mass (LVM), evaluated by echo and on "casual" and 24-h ambulatory blood pressure (24-h BP) in normotensive subjects with exaggerated blood pressure response to exercise (Group I) and in weight--and age--matched mild-moderated hypertensive patients (Group II), all with high left ventricular mass. PATIENTS: Placebo, lisinopril and diltiazem, were administered for 5-6 months in respectively 8+9+9 subjects of Group I and 8+9+10 patients in Group II. RESULTS: Placebo did not change either LVM index or 24-h BP values in Group I and Group II. Diltiazem and lisinopril reduced LVM index in both Groups I and II but 24-h BP values were only reduced in Group II. Lisinopril appeared to be more potent than diltiazem on LVM regression. Slopes of LVM index regression were not different between Groups I and II for each drug. Drug-induced changes of LVM index did not correlate with blood pressure changes. CONCLUSIONS: Drug-induced regression of LVM may be achieved in man (Group I) without any reduction of blood pressure. This may be explained by interference with growth-promoting systems other than with cardiac unloading. Also, the similar pattern of LVM regression that was observed in both Groups I and II suggests that similar underlying mechanisms may be involved in the LVH regression in these two populations.

Adult↗
PubMed1996

[Epidemiologic features of congestive heart failure. Retrospective analysis of 2561 hospitalizations].

OBJECTIVES: The aim of this study was to characterise the epidemiology of congestive heart failure namely assessing demographic, etiologic and prognostic aspects, and the hospital admission trends in the last 6 years. METHODS: Retrospective analysis of computerised data concerning patients with congestive heart failure admitted to the department of Internal Medicine. LOCATION: A central hospital in the North of Portugal. SUBJECTS: Two thousand five hundred and sixty-one patients older than 10 years, admitted to the Internal Medicine Department of a central hospital in the North of Portugal between January 1, 1989 and December 31, 1994 and discharged with the principal or first listed diagnosis of congestive heart failure (ICD-9-CM code 4280). RESULTS: Eighty per cent of the patients had more than 60 years of age and the mean age was 69 years (female: 70.40 +/- 12.65; male: 66.24 +/- 12.25; p < 0.0001). Fifty-four per cent were females and 46 per cent males. The prevalence of congestive heart failure in the Internal Medicine Department was 4.8%. Between the ages of 15 and 44 years the hospital age-specific prevalence was between 16.1/10,000/year and 26.7/10,000/year for women and between 14.5/10,000/year and 16.1/10,000/year for men. For ages equal or greater than 75 years it was between 508.9/10,000/year and 561.3/10,000/year for women and between 300.2/10,000/year and 421.8/10,000/year for men. Possible causes of congestive heart failure were: valve disease in 26 per cent of patients, coronary artery disease in 24 per cent and hypertension in 20 per cent. The average case-fatality rate was 15.15% (female: 15.54%; male: 14.69%; chi 2 = 0.36; p > 0.55) evolving from 19.45% in 1989 to 12.59% in 1994 (chi 2 = 6.85; p < 0.01). Between the ages of 15 and 44 years the hospital cause-specific mortality rate was 16.2/100,000 and for ages equal or greater than 75 years it was 743.6/100,000. Stepwise logistic regression produced the following odds ratios for the variables significantly associated with dead during hospital admission: age (> or = 70 years)--1.48; infectious diseases--1.37; central nervous system diseases--2.28; chronic renal diseases--1.96; cardiac arrest--24.1; pulmonary embolism--2.26; acute renal failure--7.93; clinical signs of severe sodium and water retention--1.49; hyponatremia--3.39; other electrolyte abnormalities and acid-base balance disturbances--1.78. The simple linear regression of daily admissions on time produced a positive slope of 0.0002 (p < 0.002). CONCLUSIONS: The hospital prevalence of congestive heart failure is identical to other Western countries and is greater among the elderly patients. Valve disease, coronary artery disease and hypertension are the most frequent causes of congestive heart failure. An increasing trend in hospital admissions for congestive heart failure was observed. The hospital mortality was reduced in the last 6 years and was greater among the elderly patients. Age (> or = 70 years), the presence of comorbidity (infectious disease, central nervous system disease, acute renal failure, chronic renal disease and pulmonary embolism), hyponatremia, other electrolyte abnormalities and acid-base balance disturbances, resuscitated cardiac arrest and the presence of severe sodium and water retention have prognostic significance.

Aged↗
PubMed1996

[Pharmacologic treatment of acute myocardial infarction: 2 large clinical trials at a central hospital].

OBJECTIVES: To analyse the clinical practice concerning the pharmacological therapy of acute myocardial infarction (AMI), comparing it with the guidelines for the management of AMI and exploring the reasons for its under use or over use. METHODS: Retrospective analysis of clinical records of patients with the discharge diagnosis of AMI. LOCATION: A central hospital in the North of Portugal. SUBJECTS: One hundred and ninety-one patients admitted to the Internal Medicine Department of a central hospital in the North of Portugal between January 1, 1993, and December 31, 1994. RESULTS: Thrombolytic therapy was performed in 24.1% of the patients. At discharge 32.6% of the patients were on therapy with beta blockers, 68% with angiotensin converting enzyme inhibitors (ACEI) and 88.4% with aspirin. Stepwise logistic regression produced the following odds ratios for the variables significantly associated with: a) thrombolytic therapy: hypertension - 0.38; non-Q wave infarction - 0.17; time between onset of symptoms and hospital admission greater than 6 hours - 0.18; admission to coronary unit - 14.72; b) beta blocker therapy: age > 60 years - 0.23; serum LDH > 1000 U/L - 0.41; diastolic blood pressure > 85 mmHg - 3.73; Killip > 1 - 0.08; concomitant therapy with calcium antagonist - 0.33; previous therapy with beta blocker - 14.87; hospital stay greater than 10 days - 2.67; c) ACEI therapy: anterior wall infarction - 3.07; non Q wave infarction - 0.13; congestive heart failure - 9.36; serum creatinine > or = 15 mg/dl - 0.03. CONCLUSIONS: Beta blockers and thrombolytic are under used and ACEI overused. The delay in hospital admission is the most important factor opposing the use of thrombolytic therapy, imposing the need for measures that ean reduce this delay. Therapy with beta blockers (highly cost-effective) can be increased by educational intervention among the physicians. The overuse of ACEI can be ascribed to the good results of randomised trials.

Adrenergic beta-Antagonists↗
PubMed1995

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. DESIGN AND METHODS: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. CONCLUSIONS: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Release and disposition of 3H-noradrenaline in the saphenous vein of neonate and adult dogs.

Release of 3H-noradrenaline and formation of 3H-metabolites were studied in the saphenous vein of newborn (mean age, 18 h) and adult dogs. Vein strips were incubated with 0.23 mumol/l of 3H-noradrenaline during 1 h and washed out for 110 min; thereafter, the perifusion fluid was collected in 5-min samples. Electrical stimulation was applied at 120 min (1 Hz, 2 ms, 100 V, for 5 min). In some experiments the tissues were preincubated with 1 mmol/l pargyline (to inhibit monoamine oxidase). In these experiments, 12 mumol/l cocaine (to inhibit uptake1), 41 mumol/l hydrocortisone (to reduce uptake2) and 50 mumol/l U-0521 (to inhibit COMT) were present during the perifusion. 3H-noradrenaline, 3H-DOPEG, 3H-NMN, 3H-DOMA and 3H-OMDA were separated by column chromatography. The noradrenaline content of the tissue was estimated by HPLC followed by electrochemical detection. A morphological study was also carried out by light and electron microscopy. The endogenous noradrenaline content of the saphenous vein was 4.3 times higher in adults than in neonates. The number of varicosities was similar in adults and newborns but the number of vesicles per varicosity profile was 5 times higher in adults. Hence, the endogenous noradrenaline content per vesicle was about the same in adults and newborns. The accumulation of 3H-noradrenaline per vesicle was about 5 times higher in newborns than in adults. On the other hand, the vein wall media of neonates was about 3 times thinner than that of adults. The evoked fractional release of tritium was about 10 times higher in neonates than in adults, whether the inactivation pathways were blocked or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

A comparative study of the distribution of tritiated and endogenous noradrenaline in the rat vas deferens and in the dog spleen capsule.

The aim of the present work was to study the influence of tissue morphological characteristics on the neuronal release (and by inference the distribution) of tritiated and endogenous noradrenaline. Rat vas deferens and dog spleen capsule were loaded with 0.2 mumol/l 3H-noradrenaline, after inhibition of the noradrenaline metabolizing enzymes. Some preparations were washed out under control conditions (spontaneous efflux) and others were washed out in the presence of the releasing agents: 40 mumol/l of Ro 4-1284 (a reserpine-like compound), 100 mmol/l potassium or 100 mumol/l tyramine. The fractional rate of loss (efflux/tissue content) of each amine was determined and the ratio "endogenous amine/3H-noradrenaline" in the efflux and in the tissue were also calculated. The results showed no preferential release of one of the amines in the spleen capsule, whereas a preferential release of tritiated noradrenaline was observed in the vas deferens. The smooth muscle layer in the vas deferens was much thicker and more compact than that of the spleen capsule. The 3H-sorbitol space was smaller in the former than in the latter. We conclude that the morphological characteristics of the tissues contribute to the differences in 3H-noradrenaline distribution in the adrenergic varicosities of these preparations.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1993

Structural changes in the hippocampal formation after long-term alcohol consumption and withdrawal in the rat.

The effects of long-term alcohol consumption and withdrawal upon the structure of the rat hippocampal formation were studied by applying morphometric methods to material processed for light and electron microscopy. The somatostatinergic neurons of the hilus were also studied. Groups of 6 rats were treated as follows: (a) given alcohol for 6, 12 and 18 months; (b) paired controls; and (c) rats switched to a normal diet in the 6 months after 6 and 12 months of alcohol intake. A progressive loss of hippocampal neurons after chronic alcohol consumption was found. The loss was aggravated during withdrawal from alcohol, with the exception of the hilar cells. The dendrites of granule cells from the alcohol-treated rats displayed signs of regrowing, but they did not do so in rats withdrawn from alcohol. The synapses between mossy fibre terminals and CA3 dendrites appear to be rather resistant to alcohol insult, and evidence of morphological plasticity was found in withdrawn rats. If an homology can be established between humans and rodents then the changes observed in alcohol-fed rats can be regarded as underpinning some of the functional and behavioural alterations depicted under these circumstances. The peculiar changes found in some nerve cell populations after withdrawal of alcohol could be related to the deficient or incomplete functional recovery often seen after abstinence from alcohol.

Alcohol Drinking↗
PubMed1991

Intracerebral grafting impedes hippocampal cell loss during withdrawal after long-term alcohol consumption in rats.

We previously found that, in the hippocampal formation as well as other central nervous system regions, withdrawal from alcohol following long periods of ingestion did not impede the ethanol-induced degenerative changes, including cell loss: on the contrary, neuronal degeneration was found to be increased in withdrawn rats. By grafting withdrawn rats either with immature hippocampal blocks or with suspensions of cultured astrocytes, we hoped to arrest the process of cell loss or even reverse it, because it is known that grafted material might display trophic and eventually protective effects in conditions of brain damage. The dentate granule and hippocampal CA3 pyramidal cells were counted both in the grafted hemisphere and in the contralateral one. Grafts of astrocyte suspensions did not interfere with the ongoing process of cell death in withdrawn rats. Conversely, grafts of hippocampal tissue impeded the degeneration observed in the granule and pyramidal cells of the grafted hemisphere, although in the contralateral one the cell loss persisted. We therefore conclude that the protective effect displayed by solid grafts might be a local process dependent on the release of diffusible trophic agents. We cannot explain the absence of any effect displayed by astroglial grafts, inasmuch as in different experimental situations such an effect was described.

Alcohol Withdrawal Delirium↗
PubMed1991

The effects of piracetam on lipofuscin of the rat cerebellar and hippocampal neurons after long-term alcohol treatment and withdrawal: a quantitative study.

There is a growing body of evidence indicating that chronic alcohol consumption induces morphological changes in the central nervous system (CNS) similar to those observed during brain senescence, including an increased formation of lipofuscin. In addition, it was also found that alcohol withdrawal does not reverse these changes. On the contrary, most of the alterations observed during alcohol consumption worsen as happens with the increased lipofuscin formation. Thus, using our model of alcohol feeding and withdrawal, we decided to examine the effects of different drugs said to offer neuronal protection during CNS degenerative processes. The action of piracetam, a cyclic derivate of GABA and commonly used as a nootropic agent, was tested by studying the lipofuscin accumulation on the cerebellar Purkinje and hippocampal CA3 pyramidal cells in alcohol-treated and withdrawn rats. Piracetam was found to markedly decrease the formation of neuronal lipofuscin. Whatever the functional implications of this pigment, its reduction in piracetam-treated animals might be related either to a protective effect on the intraneuronal membranous system or to an antioxidant property of this molecule.

Alcohol Withdrawal Delirium↗
PubMed1989

The influence of monoamine oxidase activity on the release of noradrenaline by tyramine.

The influence of monoamine oxidase (MAO) activity on the kinetic characteristics of noradrenaline (NA) release evoked by tyramine has been examined. Dog splenic artery strips were incubated with [3H]NA after inhibition of catechol-O-methyl-transferase (COMT) and of extraneuronal uptake. In some experiments MAO was also inhibited. The strips were then perifused for 200 min. Some strips were exposed to tyramine (1.5, 40 and 3240 mumols L-1) from the 100th to the 200th min of perifusion. In control experiments (i.e. in the absence of tyramine) most of the [3H]NA accumulated in the strips (83% of tissue activity) and did not contribute to the efflux. The value of this "bound fraction" (the NA located at a site(s) from which it could not be displaced by a simple concentration gradient) was the same whether or not MAO was inhibited. At all concentrations, tyramine mobilized only one NA compartment. Increasing the concentration of tyramine resulted in a decrease of the "bound fraction", which became negligible for the highest concentration of tyramine used (3240 mumols L-1), regardless of MAO being inhibited or not. However, for the lower concentrations of tyramine, MAO inhibition resulted in an increase in the amine's releasing effect. The formation of 3,4-dihydroxy-phenylglycol (DOPEG) increased with increase of tyramine from the 1.5 to 40 mumols L-1 concentration, but not beyond. The ratio NA/DOPEG increased for all concentrations of tyramine. Thus, it was not possible to exclude an inhibitory effect of tyramine on MAO activity with the highest concentration used.

Animals↗