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Biomedical subjects

L M Gonçalves

Publications and source records attributed to L M Gonçalves.

At least 19 recordsLinked to original sources

beta 2-glycoprotein I (apolipoprotein H) modulates uptake and endocytosis associated chemiluminescence in rat Kupffer cells.

beta 2-Glycoprotein I (beta 2 GPI) is known to influence macrophage uptake of particles with phosphatidylserine containing surfaces, as apoptotic thymocytes and unilamellar vesicles in vitro. Nevertheless, effects upon macrophage activation induced by this interaction are still unknown. beta 2 GPI influence upon the reactive species production by Kupffer cells was evaluated in order to investigate whether beta 2 GPI modulates the macrophage response to negatively charged surfaces. Chemiluminescence of isolated non-parenchymal rat liver cells was measured after phagocytosis of opsonized zymosan or phorbolymristate acetate (PMA) stimulation, in the presence and absence of large unilamellar vesicles (LUVs) containing 25 mol% phosphatidylserine (PS) or 50 mol% cardiolipin (CL) and complementary molar ratio of phosphatidylcholine (PC). beta 2 GPI decreased by 50% the chemiluminescence response induced by opsonized zymosan, with a 66% reduction of the initial light emission rate. PMA stimulated Kupffer cell chemiluminescence was insensitive to human or rat beta 2 GPI. Albumin (500 micrograms/ml) showed no effect upon chemiluminescence. beta 2 GPI increased PS/PC LUV uptake and degradation by Kupffer cells in a concentration-dependent manner, without leakage of the internal contents of the LUVs, as shown by fluorescence intensity enhancement. LUVs opsonized with antiphospholipid antibodies (aPL) from syphilitic patients increased light emission by Kupffer cells. Addition of beta 2 GPI to the assay reduced chemiluminescence due to opsonization with purified IgG antibodies from systemic lupus erythematosus (SLE or syphilis (Sy) patient sera. A marked net increase in chemiluminescence is observed in the presence of Sy aPL antibodies, whereas a decrease was found when SLE aPL were added to the assay, in the presence or absence of beta 2 GPI. At a concentration of 125 micrograms/ml, beta 2 GPI significantly reduced Kupffer cell Candida albicans phagocytosis index and killing score by 50 and 10%, respectively. The present data strongly suggest that particle uptake in the presence of beta 2 GPI is coupled to an inhibition of reactive species production by liver macrophages during the respiratory burst, supporting the role of beta 2 GPI as a mediator of senescent cell removal.

Animals↗

In vitro response of the brown bullhead catfish (BB) and rainbow trout (RTG-2) cell lines to benzo[a]pyrene.

Established cell lines from rainbow trout (RTG-2) and brown bullhead catfish (BB) were evaluated as bioindicators of benzo[a]pyrene (B[a]P) toxicity with 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and neutral red (NR) uptake assays. Cytochrome P450 1A1 (CYP1A1) enzymatic activity was also evaluated, and taken as a biological indicator of the B[a]P induction power by ethoxyresorufin O-deethylase (EROD) and ethoxycoumarin O-deethylase (ECOD) assays. The BB and RTG-2 cells were compared after 1 and 6 days of exposure to B[a]P. The photoactivation of the compound (B[a]PUV) was another parameter taken into consideration. Cytotoxicity was not observed after 1 day of incubation with B[a]P in both cell lines, although the enzymatic activities of ECOD and EROD presented an induction. Apparently, after 1 day, cells did not metabolise sufficient amounts of B[a]P to cytotoxic metabolites. After 6 days of exposure to this compound a significant reduction in cell viability was observed, this reduction being superior to 50% at the highest B[a]P concentrations for the RTG-2 cell line. These results are in agreement with the values observed for the ECOD and EROD induction. The B[a]P cytotoxicity determined in both cell lines could be ascribed to the significant increase of EROD activity by 6 days of exposure. The photoactivation of B[a]P showed marked differences in both cytotoxic assays and CYP1A1 enzymatic activities, for both cell lines. After 1 day of exposure there was a significant reduction in cell viability, superior to 50% for the RTG-2 cell line. However, it was observed that no induction occurred but rather a decrease in ECOD and EROD activities. Six days of incubation with B[a]PUV showed a decrease in cell viability at the highest concentrations for the BB cells and at the lowest concentrations for the RTG-2 cell line, and the CYP1A1 enzymatic activity presented a significant induction. These results and those observed after 1 day of exposure suggest that B[a]PUV acts as a direct-acting toxicant as well as a metabolism-mediated toxicant-like B[a]P. The RTG-2 cells were more sensitive to B[a]P and its toxic metabolites as well as to the photoactivation of the compound, in both exposure times tested. The finding that the cell lines responded to the CYP1A1 induction in a very efficient way gives proof of the applicability of this system to environmental biomonitoring and toxicology.

7-Alkoxycoumarin O-Dealkylase↗

Angiogenic growth factors: potential new treatment for acute myocardial infarction?

In models of hind-limb ischemia and progressive coronary artery occlusion, angiogenic growth factor proteins and genes expressing growth factors have been shown to induce the development of collateral vessels and remodeling of existing collaterals. The therapeutic potential of growth factors in the setting of acute myocardial infarction may be related to non-angiogenic properties of growth factors as well, and is the focus of this review.

Animals↗

Identification of an Arg403Gln beta myosin heavy chain gene mutation in a Portuguese family with hypertrophic cardiomyopathy.

INTRODUCTION: The etiology of Familial Hypertrophic Cardiomyopathy (HCM) is attributed to the mutation of genes that encode sarcomeric proteins in the heart. Until now no gene mutations had been identified in Portuguese families with HCM. OBJECTIVE: The main objective of this study is to describe a Portuguese family with HCM carrying an Arg403Gln mutation in the beta myosin heavy chain gene. METHODS: With the help of several Molecular Biology tools, 40 families with HCM were studied. In all these families, one member was identified as carrying an Arg403Gln mutation in the beta myosin heavy chain gene. All family members were submitted to a physical exam, EKG and echocardiography. Those carrying a gene mutation were also submitted to Holter monitoring and to magnetic ressonance imaging. RESULTS: Molecular biology techniques are extremely important for the diagnosis of HCM, particularly in healthy carriers. CONCLUSION: The use of molecular diagnostic tools in HCM is very useful because it allows us to identify the healthy carriers and establish earlier clinical and prevention programs for these individuals.

Amino Acid Substitution↗

Left ventricular dysfunction and cytoprotection.

With the projections of increasing aging of the population, heart failure is expected to become a major health problem for most Western societies. Therefore, the study of the pathophysiological mechanisms involved in heart failure should be one of the main priorities of cardiovascular research. A substantial amount of knowledge has been gathered in the recent years on the mechanisms involved in the development of heart failure. One such mechanism is the development of myocyte's apoptosis. This apoptotic mechanism is responsible for a substantial decrease in the number of cardiac myocytes, and therefore for the worsening of heart failure. This apoptotic mechanism can be triggered by a number of mechanisms such as the adrenergic stimulation, the angiotensin II production, changes in calcium homeostasis, and changes in cellular metabolism. At least in theory, the development of therapies (such as beta blockers, ACE inhibitors, calcium channel blockers and trimetazidine) that can inhibit these mechanisms can have a cytoprotective role and therefore reduce the development of heart failure. Because of its main role in the production of energy for the cell, the mitochondrion is one of the mainframes of cell viability. If the mitochondrial function is decreased the myocyte will be in jeopardy. Therefore, drugs that can prevent mitochondrial dysfunction will obviously have a cytoprotective role in heart failure.

Cytoprotection↗

[Left ventricular filling in young patients with systemic lupus erythematosus in stable phase].

OBJECTIVE: The aim of this study was to evaluate the left ventricle filling pattern in patients with stable systemic lupus erythematosus (SLE). METHODS: This prospective study was performed in 22 healthy controls and in 24 patients with stable SLE. These two groups were submitted to a clinical, electrocardiographic and echocardiographic evaluation. RESULTS: Gender distribution and mean age were similar in both groups (p = NS). Patients with SLE were more symptomatic (21%) than control patients (0%) (p < 0.01). Left ventricular dimensions, wall thickness, and systolic function were not significantly different between the two groups. However, pericardial effusion was more frequently found in patients with SLE (21%) when compared to the control group (0%) (p < 0.05). When compared to the control group, patients with SLE showed an abnormal left ventricular filling pattern. Peak late mitral flow velocity was 0.45 +/- 0.2 m/sec in SLE patients and 0.36 +/- 0.1 m/sec in the control group (p = 0.001). CONCLUSION: These results demonstrate that patients with stable SLE, when compared to healthy controls, are frequently associated with cardiovascular symptoms, asymptomatic pericardial effusion, and an abnormal left ventricular filling pattern.

Adult↗

[Changes in the geometry of the heart cavities in patients with cardiac tamponade undergoing pericardial drainage].

OBJECTIVES: The objective of our study was to evaluate the changes in cardiac chamber dimension--longitudinal and transversal axis--in patients with cardiac tamponade after drainage of the pericardial effusion. STUDY DESIGN: This is a five year retrospective study (from 1991 to 1995 inclusive) which evaluates patients with cardiac tamponade from a clinical and electrocardiographic, as well as echocardiographic, point of view. MATERIALS AND METHODS: Thirty-nine consecutive patients with cardiac tamponade were evaluated clinically and by ECG and two-dimensional echocardiography, before and after drainage of the pericardial effusion. The drainage was done by pericardiocentesis alone in 28 cases (72%), pericardiocentesis followed by surgery in seven cases (18%) and surgery alone in four cases (10%). MAIN RESULTS: After drainage we observed a reduction in the diameter of the pericardial effusion from 30.1 +/- 8 to 8.1 +/- 7 mm; the occurrence of jugular vein turgescence decreased from 87% to 5% (p < 0.001) and heart rate also decreased from 100 +/- 20 beats/minute to 79 +/- 17 beats/minute (p < 0.001). Systolic blood pressure increased from 107.8 +/- 20.4 mmHg to 134.6 +/- 20.3 mmHg (p < 0.001). All longitudinal and transversal diameters of the cardiac chambers increased after drainage. The greatest increase was observed in the transversal diameters of the right chambers. CONCLUSIONS: Cardiac tamponade affects both right and left cardiac chambers which are affected in their transversal as well as longitudinal diameters; the effect of compression was more marked in the right chambers and in the transversal diameters.

Adolescent↗

Fibroblast growth factor-mediated angiogenesis for the treatment of ischemia. Lessons learned from experimental models and early human experience.

Fibroblast growth factors (FGFs) are a family of nearly twenty heparin-binding growth factors. They are widely distributed throughout the body, but their activity is tightly controlled. This review will focus on fibroblast growth factor-1/FGF-1) and fibroblast growth factor-2 (FGF-2) which have been studied extensively in vitro and in vivo. These two growth factors stimulate the proliferation of cells of mesenchymal origin, including the three principal vascular cell types: fibroblasts, endothelial cells and smooth muscle cells. The molecular characteristics of these growth factors, their receptors, distribution, function, pharmacokinetics, hemodynamic effects and toxicity are reviewed herein. The experimental evidence for the potential for FGFs as therapeutic agents for the treatment of progressive myocardial ischemia, acute myocardial ischemia, and peripheral limb ischemia is also analyzed. It is not known to what extent the results of animal studies can be extrapolated to humans with ischemic cardiovascular disease. Clinical trials have been initiated, and there is a growing hope that the pharmacologic use of growth factors will represent a viable therapeutic alternative for patients with ischemic cardiovascular disease.

Animals↗

[Correlation between aortic transvalvular gradient obtained with Doppler ultrasonography and with hemodynamics study. Role of the underlying etiology].

In aortic stenosis, a good correlation was found between the gradients obtained by catheterization and Echo-Doppler. However, the correlation of these two methods in subgroups of patients with different etiologies of aortic stenosis is unknown. The aim of this study was to evaluate, whether the correlation between catheterization and Echo-Doppler was similar in patients with different etiologies of aortic stenosis. Patients with concomitant valvular disease were excluded. Only patients with a clearly defined etiology (based on clinical history, echocardiography, angiography and/or pathology) were included in this study. We evaluated 106 patients with aortic stenosis. Forty-nine patients had degenerative aortic stenosis, 32 bicuspid aortic stenosis and 25 rheumatic aortic stenosis. The percentage of male patients in each group were as follows: 57.1% in the denerative aortic group; 62.5% in the bicuspid aortic stenosis group; and 76% in the rheumatic aortic stenosis group. Mean age (years) was 69 +/- 6.7 in the degenerative aortic stenosis group, 58.1 +/- 7.5 in the bicuspid aortic stenosis group, and 64 +/- 7.1 in the rheumatic aortic stenosis group. In our study we found different correlations between the gradients obtained by the two methods-catheterization and Eco-Doppler-among the patients with different etiologies of aortic stenosis. The correlation coefficient (r2) was 0.54 (p < 0.001) in the rheumatic aortic stenosis group, 0.37 (p < 0.001) in the bicuspid aortic stenosis group and 0.21 (p = 0.001) in the degenerative aortic stenosis group. In conclusion, a good overall correlation was found between the two methods in aortic stenosis, however, this correlation is different in the three etiologies of aortic stenosis. The correlation is better in rheumatic valves, intermediate in bicuspid valves, and worse in degenerative valves. Changes in aortic valve morphology in these subgroups of patients are probably responsible for these different results.

Aged↗

Evaluation of pulmonary systemic blood flow using ECG gated acquisition.

We propose a functional parametric analysis method using ECG-gated 99mTc-labeled red blood cell (RBC) imaging for detection and characterization of periodic variations in local blood activity in the lungs during cardiac cycle. We validated in animal experiments that such count variations correlate with cyclical pulmonary blood flow and may be used for evaluation of systemic-to-pulmonary shunts. Clinical studies were performed in 48 patients. After labeling the RBC pool with 99mTc, ECG-gated gamma camera images of both lung fields were acquired and processed to obtain Fourier transforms of time/activity functions in selected regions. The first harmonic parametric images of amplitude and phase were derived. There was an excellent correlation (r = 0.92) between activity variations and pulsatile flow measured by our method with that obtained by the thermodilution method in dog experiments (n = 10) after implantation of a systemic-to-pulmonary shunt. Patient studies showed the technique to be sensitive in detecting and quantifying abnormal systemic-to-pulmonary blood flow. Lung pulsatile flow can thus be noninvasively measured from functional parametric phase and amplitude images; the technique may be useful for detecting and quantifying abnormal systemic-to-pulmonary blood flow in man.

Animals↗

[Biology of Biomphalaria occidentalis Paraense, 1981 and Biomphalaria tenagophila (d'Orbigny, 1835), in laboratory conditions].

Specimens of Biomphalaria occidentialis and Biomphalaria tenagophila were reared in S. Paulo, Brazil under laboratory conditions, with a view to know their biological characteristics. Oviposition and eggs/oviposition ratio were recorded over twelve months so as to obtain information on the number of egg-masses per animal and the number of eggs per egg-mass, as also the number of hatched eggs per egg-mass for each period of 30 days, i.e., the hatching-rate per period. The incubation period was about the same for both species, but the oviposition and egg oviposition ratio were greater in B. tenagophila.

Animals↗

Modification of antihypertensive effect of beta-adrenoceptor-blocking agents by inhibition of endogenous prostaglandin synthesis.

The effect of indomethacin-induced inhibition of endogenous prostaglandin synthesis on the antihypertensive activity of pindolol (15 mg daily) and propranolol (80--160 mg daily) was studied in 7 hypertensive patients. In four test phases of 10 days each, patients received beta-blocker alone, placebo, beta-blocker plus indomethacin (100 mg daily), and beta-blocker alone. Mean supine diastolic blood-pressure rose from 82 +/- 2 mm Hg in the first beta-blocker phase to 98 +/- 3 mm Hg in the placebo phase, remained elevated (96 +/- 3 mm Hg) in the beta-blocker-plus-indomethacin phase, and fell to 83 +/- 3 mm Hg in the last beta-blocker phase. Diastolic blood-pressure values obtained in the beta-blocker-plus-indomethacin phase were not significantly different from those obtained in the placebo phase but were significantly different from the values measured in both beta-blocker phases (P less than 0-01). The changes in systolic blood-pressure and pulse-rate were not significant. These preliminary results suggest that the antihypertensive effect of these two beta-blockers in some hypertensive patients may be related to the endogenous prostaglandin system.

Adult↗

[A survey of Planorbidae in the state of São Paulo: the 8th Administrative Region (the greater São Jose do Rio Preto area)].

In order to know the distributional patterns of Basommatophoran snails in the state of São Paulo (Brazil), 85 "counties" in the area of S. José do Rio Preto were worked out during seven months (1982). Snails from 286 breeding places were collected and identified. Biomphalaria straminea, an intermediate host of S. mansoni, was found in four little ponds, in the neighbourhood of Altair and S. José do Rio Preto. It was concluded that schistosomiasis has little chance to spread out in the studied area.

Animals↗