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Biomedical subjects

J Martins e Silva

Publications and source records attributed to J Martins e Silva.

At least 19 recordsLinked to original sources

Ischemic myocardial disease as an example of a thrombotic event. A historical note.

The definition of myocardial ischemia as a clinical entity of thrombotic etiology was established in 1912 by James Herrick. His proposal was based on the work of William Heberden, who in 1772 defined the clinical profile of angina pectoris, and the observations of Edward Jenner about a century later on intracoronary thrombosis in patients who had died with such symptoms. On the basis of these results, Jenner and Caleb Parry proposed that the main cause of angina were alterations in the coronary arteries, while Marshall Hall, in 1842, attributed sudden death in these patients to interruption of the coronary circulation. The discovery of a common cause for angina pectoris and myocardial infarction, inducing a reduction or interruption of oxygen supply to myocardial tissue, the atherosclerotic etiology of intracoronary lesions, and the importance of plaque fissuring in the sudden formation of intracoronary thrombi, were successive milestones in our understanding in the 20th century, the culmination of the process of meticulous observation begun many years before.

Humans↗

Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction.

The objective of this study was to evaluate the long-term predictive value of the haemostatic, inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 +/- 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leukoactivity, leukocyte count, membrane fluidity, prognosis cyte count (7833.0 +/- 1696.0 vs. 10294.0 +/- 3129.0; p = 0.011), lower PtC (100.65 +/- 19.08 vs.81.25 +/- 19.95; p = 0.002), and lower erythrocyte aggregation (14.26 +/- 5.94 vs. 11.47 +/- 3.45; p = 0.031) in relation to the ones without events; (ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045-0.628; p = 0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 - 0.393; p = 0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 - 0.876; p = 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances, at hospital discharge, are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.

Adult↗

An in vitro study of adrenaline effect on human erythrocyte properties in both gender.

The possibility that erythrocytes may function as a reservoir for noradrenaline and adrenaline and as a modulator of circulating catecholamine concentrations had been suggested. The aim of this work was to study the adrenaline effect on erythrocyte membrane fluidity, acetylcholinesterase (AChE) enzyme activity, P(50) and erythrocyte deformability and also to verify if the role of adrenaline on erythrocyte properties is sex-dependent. Blood samples from 42 healthy donors were obtained, and its aliquots incubated 30 min without (control) and with 10(-5) M concentrations of adrenaline alone (A(1)) and adrenaline with an alpha and an beta-blocker (A(2)). Results demonstrate that initial AChE values in female are higher (p<or=0.01) than male values. In female, adrenaline decreases AChE activity either when alpha and beta-adrenergic receptors are blocked (p<or=0.01) or when they are not. In male, adrenaline increases AChE activity when none of adrenergic receptors are blocked. Control values of male and female erythrocyte membrane fluidity are very similar but behaviour became differently (p<or=0.05) when adrenaline is present because it decreases male and increases female values. Gender differences in erythrocyte deformability are verified at high shear stress values (p<or=0.02). In female we have also registered the existence of an inverse significant correlation (r=-0.62) between membrane rigidity and AChE activity in A(2) values. Adrenaline increases p(50) values (p<or=0.03) in both sexes. Peripheral blood film has shown echinocytes when adrenaline 10(-5) M is present. We conclude that in this in vitro study sex-related differences in erythrocyte acetylcholinesterase enzyme activity, membrane fluidity and erythrocyte deformability under adrenaline influence were found.

Acetylcholinesterase↗

[Biohemorheologic factors and cardiovascular events curve in survivors of transmural acute myocardial infarct--24-month follow-up].

INTRODUCTION: Previous reports have shown several biohemorheological disturbances in acute myocardial infarction (AMI), either in the acute phase and after hospital discharge. There is no clearly established relationship between these parameters and the patients' clinical outcome. OBJECTIVE: To evaluate in transmural AMI survivors, a relationship between biohemorheological parameters and the cardiovascular events curve during a 24 month follow-up period. METHODS: Sixty-four consecutive patients (58.0 +/- 12.0, 59 men), transmural AMI survivors (30 anterior and 34 inferior) were included in the study. Clinical follow-up was 24 months (at 6, 12 and 24 months). The following cardiovascular events (CVE) were collected: cardiovascular death, stroke, AMI, unstable angina, embolism. We determined, at hospital discharge, these biohemorheological parameters: plasma viscosity, fibrinogen, PAI-1 inhibitor, leukocyte count, C protein (C Pt), erythrocyte aggregation (EA). For each parameter we determined the 25, 50 and 75 percentiles and other significant cut-off point, grouping patients according to these values. STATISTICS: Group t test, Kaplan-Meier survival curve (with the log rank test), and Cox logistic regression. RESULTS: (1) Patients with CVE (n = 19) during the 24 months of clinical follow-up had at hospital discharge higher leukocyte count (p < 0.001), lower C Pt (p < 0.01) and lower EA (p < 0.05). (2) The higher the percentile of the leukocyte count higher the probability for a CVE. Patients with leukocyte count above the 50 percentile had 6 times more CVE (p < 0.01); (3) The higher the C Pt lower the risk for a CVE. Patients with C PT lower than the 50 percentile had 9 times more risk for a CVE (p < 0.01), and those above the 75 percentile had no CVE (p < 0.01). (4) For the EA we identified a cutoff point (= 14.5), independent of the percentiles values. Patients with EA below 14.5 had six times more CVE. By multivariate analyses, we identified leukocyte count and C Pt as independent risk predictive factors (p < 0.05). CONCLUSION: In this group of transmural MI survivors a relationship was established between some biohemorheological (leukocyte count, C Pt, EA) and the CVE curve during 24 months of clinical follow-up.

Blood Viscosity↗

Nitric oxide effects on human erythrocytes structural and functional properties--an in vitro study.

NO is present in the blood at 10(-7) M under physiological conditions, but at concentrations higher than 10(-6) M during inflammatory disease states. The aim of this study was to characterize what are the effects of these different NO concentrations on erythrocyte structural and functional properties. Blood was collected from eleven healthy men and incubated with SpermineNONOate in order to expose it during incubation time to NO concentrations between 10(-7) M and 10(-3) M. We measured erythrocyte aggregation and deformability, membrane lipid peroxidation and fluidity, p50, hemoglobin, oxyhemoglobin, methemoglobin concentrations and plasma pH, pO(2), pCO(2), Na(+), K(+) and Ca(2+). When blood was exposed to NO 10(-7) M erythrocyte deformability increase and p50 decrease. In presence of NO 10(-5) M lipid fluidity and p50 decrease. When blood was exposed to NO 10(-3) M methemoglobin concentration increase and erythrocyte deformability and p50 decrease but membrane fluidity and lipid peroxidation were similar to control. In conclusion, dependent of NO concentrations there is different effects on erythrocytes structural and functional properties.

Adult↗

Long-term prognostic value of the hemorheological profile in transmural myocardial infarction survivors: 60-month clinical follow-up.

UNLABELLED: Previous reports have shown several hemorheological and hemostatic abnormalities in acute coronary syndrome survivors. Some of these abnormalities were related to cardiovascular events during a 24-month follow-up. The aim of the present work is to evaluate, in transmural myocardial infarction survivors, the long-term (60 months) prognostic value of the biohemorheological profile determined at hospital discharge. Sixty-four patients (59 men), mean age of 58 +/- 12.0 years, transmural myocardial infarction survivors, were prospectively studied for 60 months (32.0 +/- 17 months, median 33 months). The following cardiovascular events (CVE) were analyzed: death, non-fatal infarction, unstable angina, and stroke. Twenty-nine patients had a CVE (nine died). The following parameters were determined at hospital discharge: plasma viscosity, whole blood viscosity, erythrocyte membrane fluidity, erythrocyte aggregation, protein C, plasminogen inhibitor type I (PAI-1), leukocyte count and elastase. The quartiles were determined for each parameter, grouping patients according to these values. STATISTICS: Group-t-test, Kaplan-Meier survival curve (with log rank test), and Cox logistic regression. RESULTS: 1) Leukocyte count (p < 0.01), protein C activity (p < 0.05) and erythrocyte membrane fluidity (p < 0.05) were predictors of the CVE curve; 2) The higher the value of the leukocyte count quartile, the higher the risk for a CVE (p < 0.05). Patients with a leukocyte count above the median had 4 times more risk for a CVE; 3) The lower the protein C activity, the higher the risk for a CVE. Those with protein C activity lower than the lowest quartile had double the risk; 4) The higher the membrane polarization value (membrane rigidity), the higher the risk of a CVE; 5) By multivariate analysis the 3 parameters were independent predictors of a CVE. CONCLUSION: In the present group of transmural myocardial infarction survivors a close relationship was established between hemorheologic, hemostatic and inflammatory factors and the cardiovascular events curve during long-term follow-up.

Female↗

Beta-estradiol effect on erythrocyte aggregation--a controlled in vitro study.

The purpose of this in vitro study was to assess the effect of 17beta-estradiol on hemorheologic parameters, namely on erythrocyte aggregation and deformability and membrane fluidity. Blood samples from 65 women (aged 57 +/- 4 years) undergoing postmenopausal hormone replacement therapy were obtained and were incubated for 5 min in absence and presence of 17beta-estradiol 10(-5) M. The measured parameters were the erythrocyte aggregation (EAI) and deformability (EI), the acetylcholinesterase activity (AChE), the plasma pH and osmolality and the erythrocyte membrane fluidity assessed by fluorescence polarization with two probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and (1-(4-(trimethylamino)-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Data analysis was performed using t-Student and Pearson correlation analysis. A statistically significant decrease of the EAI (15.8 +/- 3.02 vs 13.45 +/- 2.3; p<0.001) and an increase of the EI (51.39 +/- 5.64 vs 52.06 +/- 5.36; p<0.01) at shear stress of 30 Pa in presence of 17beta-estradiol 10(-5) M was obtained. There was a decrease in membrane fluidity in 45 blood samples (DPH) and in the other 20 an increase, when beta-estradiol 10(-5) M was present. In vitro beta-estradiol 10(-5) M decreased erythrocyte aggregation in blood samples of postmenopausal women undergoing hormone therapy, which could prevent high blood viscosity and, consequently, cardiovascular events.

Acetylcholinesterase↗

Red blood cell membrane integrity in primary open angle glaucoma: ex vivo and in vitro studies.

PURPOSE: There is increasing evidence that abnormal perfusion of the optic nerve head is an important factor involved in the pathophysiology of glaucoma. Transport and distribution of oxygen to the tissues takes place through the erythrocyte membrane. Red blood cell (RBC) acetylcholinesterase (AChE) is a marker of RBC membrane integrity. The aim of this study was to find out whether RBC membrane integrity is preserved in primary open angle glaucoma (POAG), and whether it is modified by the use of topical timolol maleate and pilocarpine. METHOD: RBC AChE activity was determined ex vivo by Kaplan's spectrophotometric method in 19 POAG patients undergoing topical treatment for glaucoma with timolol, pilocarpine or a combination of the two drugs, and compared with that in 20 controls. To assess the effect of antiglaucomatous therapy in our findings, we carried out an in vitro study in 26 non-glaucomatous patients in which we measured RBC AChE activity after incubation of blood with either timolol maleate, pilocarpine or a combination of the two drugs, using the same spectrophotometric method. RESULTS: There was a significant increase in RBC AChE enzyme activity in POAG patients compared with the control group (p < 0.002). However, timolol and pilocarpine, individually or in combination, have the opposite effect, significantly decreasing RBC AChE activity (p < 0.05). CONCLUSION: This change in RBC AChE enzyme activity could suggest alterations in RBC membrane integrity in primary open angle glaucoma. Whether or not this finding has implications regarding the microcirculation at the optic nerve head needs to be investigated further.

Acetylcholinesterase↗

Ethanol and erythrocyte membrane interaction: a hemorheologic perspective.

Previous studies have documented structural and functional changes induced by ethanol-erythrocyte membrane interaction. In order to perform an in vitro study on the effect of different ethanol concentrations on erythrocyte hemorheologic properties, blood samples were collected from 21 male donors at the Hospital of Santa Maria. Whole blood aliquots were incubated with ethanol solutions of rising concentrations. The following parameters were measured: erythrocyte aggregation, haemoglobin, carboxyhaemoglobin and methaemoglobin concentrations, hematocrit, plasma osmolality and erythrocyte membrane fluidity (fluorescence polarisation probes TMA-DPH and DPH). With ethanol blood concentrations of 45 mM a rise in plasma osmolality (0.352 Osm/kg H2O vs 0.310 Osm/kg H2O; p < 0.001) was verified. With 67 mM concentration a decrease of erythrocyte aggregation (11.03 vs 12.81; p < 0.05) and an increase in plasma osmolality (0.380 Osm/kg H2O vs 0.310 Osm/kg H2O; p < 0.001) were obtained. In conclusion, ethanol only changes erythrocyte aggregation for a concentration of 67 mM. These data could lead to future changes in therapeutic approaches to situations such as alcoholic coma.

Adult↗

The effect of sodium fluorescein angiography on erythrocyte properties.

Sodium fluorescein angiography is a widely used routine ophthalmological diagnostic procedure which enables the study of chorioretinal microcirculation and consists of the injection of sodium fluorescein into the systemic bloodstream. The aim of the present study was to evaluate whether or not fluorescein interferes with erythrocyte properties during the angiographic procedure. In a group of 37 patients, 26 with non-insulin-dependent diabetes mellitus (DM) with and without retinopathy, and 11 without diabetes mellitus (non-DM) although affected by other ophthalmological diseases, all undergoing routine angiography, blood samples were drawn before (T0) and 30 min (T30) after fluorescein injection. The erythrocyte aggregation index (EAI), membrane lipid fluidity and erythrocyte acetylcholinesterase activity were determined in both groups. After fluorescein injection there was no statistical change in EAI and erythrocyte membrane fluidity in either group. Erythrocyte acetylcholinesterase activity, a marker of membrane protein integrity, decreased significantly (p < 0.01) in the DM group. Membrane lipid fluidity did not change with fluorescein injection, however (i) in the DM group erythrocyte membranes became more rigid than in the non-DM (DPH: p < 0.01); (ii) EAI and membrane lipid fluidity became significantly correlated (r = 0.6263, p < 0.05) in non-DM patients at T30. In conclusion, fluorescein administration for angiographic procedures seems to interact with erythrocyte membrane, namely, in diabetic patients, which may interfere with the blood flow in the microcirculation.

Acetylcholinesterase↗

[The directional axes in the reform of medical teaching. A strategic proposal].

The circumstances preceding the future revision of the medical curriculum are analysed, main internal and external stimuli are described, and sources of resistance to changes in medical training require new educational philosophy, privileging oriented training during undergraduation, as a preliminary phase of medical education. The definition and accompaniment of the general and specific objectives, the strategy and programme used, the design and adequacy of the available support, and the related engagement of all political, academic and socially responsible persons and institutions, are fundamental factors for successful change. The education and training of polyvalent medical doctors requires methodological modifications, namely the definition of a core curriculum, made dynamic through the teaching of interdependent subjects and earlier contact with common clinical problems. Learning through interconnected basic and clinical matters will benefit the technical and psychosocial education of future doctors. The education resulting from a renewal in undergraduate medical education will be mostly determined by organizational and institutional frameworks, teaching methods and the evaluation process used, as well as by teacher commitment, pedagogic and scientific capacities. Professional competence should be the end product of efficient training. Otherwise, undergraduate medical education would not prepare the professional development of the young doctors, thus diminishing the quality of medical training in the future.

Curriculum↗

[Limitations and perspectives of teaching and research in basic sciences at the Portuguese Faculties of Medicine].

Well known difficulties of teaching and research lived by basic sciences of the medical school curriculum in Portugal are becoming desperate. Two main problems deserve major concern and urgent solutions: firstly, the recruitment and continuing formation of motivated candidates for teaching and/or research in those areas; secondly, the establishment of adequate economic support that makes those careers in basic teaching and research attractive, along with the provision or creation of the necessary support for both activities. Specific administrative and financial solutions are required from the government, in order to foster a realistic future in the preclinical areas of the medical curricula.

Education, Medical↗

[Biochemical characterization and metabolic effects of tumor necrosis factor].

The tumor necrosis factor, preliminary identified because of its antitumor properties, refers to two kinds of similar polypeptides (TNF or cachectin, and TNF-beta or lymphotoxin), which share some biological effects. Both substances, as members of the class of cytokines, play a role as mediators of inflammation and the cellular immune response. Human cachectin is produced as a prohormone and activated by cleavage of a 76 residue peptide. Mature cachectin (which comprises 157 amino acid residues) share a 28% amino acid sequence homology with lymphotoxin. Both cytokines are encoded by different genes of chromosome 6 and may compete for a common receptor. Cachectin is produced by a wide variety of cells (phagocytic and non-phagocytic), mainly by activated macrophages and monocytes. Different invasive stimuli (mainly lipopolysaccharide, a constituent of the Gram-negative bacteria's outer wall) activate cachectin biosynthesis, which is controlled chiefly at a post-transcriptional level. The newly synthetized cachectin remains associated as a transmembrane form, affecting their targets by direct cell-to-cell contact, or is actively secreted in the circulation to distant sites in the body, where it binds to high affinity cachectin receptor, on a variety of cell types. Cachectin exerts pleiotropic effects on normal, transformed, or tumoral cells. The biological effects mediate by cachectin may be beneficial or deleterious to the body, depending on the quantity produced, duration of cell exposure and further biochemical mediators in the environment of the target cells. Cachectin (frequently associated with severe infection and cancer) seems to be the result of a persistent exposure to raised levels of cachectin.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[Hemorrheologic aspects of congestive heart insufficiency].

Congestive heart failure is characterized by increased blood volume and abnormal salt and water retention behind one or both ventricles and restricted systemic blood perfusion. Blood hyperviscosity, as one of the two major determinants of the overall resistance, also contributes significantly to the lowering of blood flow in the macrocirculation and microcirculation. The observed loss of the red cell deformability together with higher plasma viscosity and suggested increase on the aggregation of red cells, might be important factors determining blood hyperviscosity, therefore contributing for pathological situations of hypoperfusion or intravascular stagnation.

Blood Flow Velocity↗

Red cell membrane alteration involving protein 4.1 and protein 3 in a case of recessively inherited haemolytic anaemia.

We present 2 siblings with a severe congenital haemolytic anaemia. Red cells displayed a variety of abnormal shapes, including leptocytes, schizocytes and elliptocytes. Repeatedly, skeletal protein 4.1 appeared reduced by 30%. The 4.1a/4.1b ratio was normal despite the haemolytic state. No change could be detected in spectrin, nor in sialoglycoproteins. Band 3 was denser, narrower and displaced downward. The parents, who are consanguineous, were devoid of any obvious biochemical abnormality; however, their red cells were not normal. These 2 cases with reduced protein 4.1 clearly depart from 4.1 (-) hereditary elliptocytosis. The possibility of an altered binding of protein 4.1 to some other membrane component is discussed.

Adolescent↗