Mechanical versus biological aortic valve implants in the elderly. A comparison of early and mid-term results

OBJECTIVE: Our aim was to compare, in a non randomized study, the surgical outcome in elderly patients with mechanical (Group 1; n=83) and bioprosthetic valve implants (Group 2; n=136). METHODS: During a three year period, 219 patients >75 years underwent Aortic Valve Replacement. The groups matched according to age, sex, comorbidity, valve pathology and concomitant Coronary Artery Bypass Surgery. Follow-up was a total of 469 patient-years (mean follow-up 2.1 years, maximum 4,4 years). RESULTS: Operative mortality was zero and the overall early mortality was 2.3 % (within 30 days). Actuarial survival was 87.5 ± 4.0% and 66.1 ± 7.7% (NS) at 4 years in Group 1 and Group 2, respectively. Freedom from valve-related death was 88.9 ± 3.8% in Group 1 and 69.9±7.9% (NS) in Group 2 at 4 years. CONCLUSION: Aortic Valve Replacement in the elderly (>75 years) is a safe procedure even in cases where concomitant coronary artery revascularization is performed. Only a few anticoagulant-related complications were reported and this may indicate that selected groups of elderly patients with significant life expectancy may benefit from mechanical implants .

Pharmacological Therapy for Myocardial Infarction in the Elderly: An 8-year Analysis

OBJECTIVE:To assess the changes in the medicamentous treatment of elderly patients hospitalized with acute myocardial infarction occurring over an 8-year period. METHODS:We retrospectively analyzed 379 patients above the age of 65 years with acute myocardial infarction who were admitted to the coronary unit of a university-affiliated hospital from 1990 to 1997. The patients were divided into 2 groups, according to the period of time of hospital admission as follows: group 1 - from 1990 to 1993; and group 2 - from 1994 to 1997. RESULTS:The use of beta-blockers (40.8%chi 75.2%, p<0.0001) and angiotensin-converting enzyme inhibitors (42% chi59.5%, p=0.001) was significantly greater in group 2, while the use of calcium antagonists (42% chi 18.5%, p<0.0001) and general antiarrhythmic drugs (19.1% chi 10.8%, p=0.03) was significantly lower. No significant difference was observed in regard to the use of acetylsalicylic acid, thrombolytic agents, nitrate, and digitalis in the period studied. The length of hospitalization was shorter in group 2 (13.4±8.9 days chi 10.5±7.5 days, p<0.001). The in-hospital mortality was 35.7% in group 1 and 26.6% in group 2 (p=0.07). CONCLUSION: Significant changes were observed in the treatment of elderly patients with acute myocardial infarction, with a greater use of beta-blockers and angiotensin-converting enzyme inhibitors and a lower use of calcium antagonists and antiarrhythmic drugs in group 2. The length of hospitalization and the mortality rate were also lower in group 2, even though the reduction in mortality was not statistically significant.

Analysis of the Association Between Apolipoprotein E Polymorphism and Cardiovascular Risk Factors in an Elderly Population with Longevity

OBJECTIVE: To establish the allelic and genotypic frequencies related to apolipoprotein E (ApoE) polymorphism and association of the genotypes with risk factors and cardiovascular morbidity in an elderly population with longevity. METHODS: We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veranópolis. We used the gene amplification technique through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The most frequent genotypes were compared considering biological variables and cardiovascular risks and morbidity. RESULTS: The frequencies of the E2, E3, and E4 alleles were 0.05, 0.84, and 0.11, respectively, and of the genotypes were as follows: E3E3 (0.70), E3E4 (0.22), E2E3 (0.06), and E2E2 (0.02). Individuals with the E3E4 had a mean age greater than those with the E3E3. No association was observed between the genotypes and the variables analyzed, except for obesity, which was associated with the E3E3 genotype. Individuals with the E3E4 genotype had high levels of LDL-cholesterol and fibrinogen as compared with those with the E3E3 genotype. CONCLUSION: The results suggest that the E4E4 genotype may be associated with early mortality. A balance between the protective or neutral factors and the cardiovascular risk factors may occur among the individuals with different genotypes, attenuating the negative effects of the E4 allele.

Proteomic analysis of nitrate-dependent acetone degradation by Alicycliphilus denitrificans strain BC

Alicycliphilus denitrificans strain BC grows anaerobically on acetone with nitrate as electron acceptor. Comparative proteomics of cultures of A. denitrificans strain BC grown on either acetone or acetate with nitrate was performed to study the enzymes involved in the acetone degradation pathway. In the proposed acetone degradation pathway, an acetone carboxylase converts acetone to acetoacetate, an AMP-dependent synthetase/ligase converts acetoacetate to acetoacetyl-CoA, and an acetyl-CoA acetyltransferase cleaves acetoacetyl-CoA to two acetyl-CoA. We also found a putative aldehyde dehydrogenase associated with acetone degradation. This enzyme functioned as a -hydroxybutyrate dehydrogenase catalyzing the conversion of surplus acetoacetate to -hydroxybutyrate that may be converted to the energy and carbon storage compound, poly--hydroxybutyrate. Accordingly, we confirmed the formation of poly-?-hydroxybutyrate in acetone-grown cells of strain BC. Our findings provide insight in nitrate-dependent acetone degradation that is activated by carboxylation of acetone. This will aid studies of similar pathways found in other microorganisms degrading acetone with nitrate or sulfate as electron acceptor.

Acute myocardial infarction in elderly patients: comparative analysis of the predictors of mortality. The elderly versus the young

OBJECTIVE: To study the in-hospital evolution of patients aged 65 years and older, with acute myocardial infarction, who were treated by direct coronary angioplasty with no fibrinolytic therapy. METHODS: We studied 885 patients divided into 2 groups as follows: group I (GI) - 293 (33.4%) patients aged ³ 65 years (72±5 years), and group II (GII) - 592 patients aged < 65 years (57±9 years). Multivessel disease was more frequent in GI (63.5% x 49.7%; p=0.001). A greater number of GII patients were class I or II of the clinical Killip-Kimball classification (K) (80.2% x 67.2%; p=0.00002), while a significant number of GI patients were KIII and KIV (24.3% x 12.8%; p=0.00003). RESULTS: Group I had a lower index of success (84.6% x 94%; p=0.0002) and a greater in-hospital mortality (12.2% x 4.7%; p=0.00007). The predictors of mortality in GI were as follows: previous infarction (20.5% x 6.3%; p=0.02), anterior location (13.4% x 6.4%; p=0.03), and male sex (10.4% x 4.4%; p=0.007). CONCLUSION: Elderly patients had more severe acute myocardial infarction and more extensive disease, a lower index of success, and greater in-hospital mortality. Previous infarction, anterior location and male sex were identified as predictors of mortality in the elderly group (GI).

Relation between the behaviors of P-wave and QT dispersions in elderly patients with heart failure

OBJECTIVE: To assess the relation between P-wave and QT dispersions in elderly patients with heart failure. METHODS: Forty-seven elderly patients (75.6±6 years) with stable heart failure in NYHA functional classes II or III and with ejection fractions of 37±6% underwent body surface mapping to analyze P-wave and QT dispersions. The degree of correlation between P-wave and QT dispersions was assessed, and P-wave dispersion values in patients with QT dispersion greater than and smaller than 100 ms were compared. RESULTS: The mean values of P-wave and QT dispersions were 54±14 ms and 68±27 ms, respectively. The correlation between the 2 variables was R=0.41 (p=0.04). In patients with QT dispersion values > 100 ms, P-wave dispersion was significantly greater than in those with QT dispersion values < 100 ms (58±16 vs 53±12 ms, p=0.04 ). CONCLUSION: Our results suggest that, in elderly patients with heart failure, a correlation between the values of P-wave and QT dispersions exists. These findings may have etiopathogenic, pathophysiologic, prognostic, and therapeutic implications, which should be investigated in other studies.

Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation

OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37ºC and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2á and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.

Fatalidade ou missão:estudo exploratório sobre as estratégias utilizadas pelas Ajudantes de Lar, para fazer face às exigências da sua profissão

Dissertação de Mestrado em Políticas de Desenvolvimento de Recursos Humanos

Mecanismo de interacción, calcio dependiente, entre Calcineurina y PERK, involucrado en el Estrés de Retículo Endoplásmico. Ca2+ -dependent mechanism of interaction between Calcineurin and PERK involved in Endoplasmic Reticulum Stress.

El Estrés de Retículo Endoplásmico (RE) es inducido por la acumulación de proteínas sin plegar en el lumen de la organela. Esto se puede observar en diversas situaciones fisio-patológicas como durante una infección viral o en proceso isquémico. Además, contribuye a la base molecular de numerosas enfermedades ya sea índole metabólico (Fibrosis quística o Diabetes Miellitus) o neurodegenerativas como mal de Alzheimer o Parkinson (Mutat Res, 2005, 569). Para restablecer la homeostasis en la organela se activa una señal de transducción (UPR), cuya respuesta inmediata es la atenuación de la síntesis de proteína debido a la fosforilación de subunidad alpha del factor eucariótico de iniciación de translación (eIF2α) vía PERK. Esta es una proteína de membrana de RE que detecta estrés. Bajo condiciones normales, PERK está inactiva debido a la asociación de su dominio luminar con la chaperona BIP (Nat Cell Biol, 2000, 2: 326). Frente a una situación de estrés, la chaperona se disocia causando desinhibición. Recientemente, (Plos One 5: e11925) se observó, bajo condiciones de estrés, un aumento de Ca2+ citosólico y un rápido incremento de la expresión de calcineurina (CN), una fosfatasa citosólica dependiente de calcio, heterodimérica formada por una subunidad catalítica (CN-A) y una regulatoria (CN-B). Además, CN interacciona, sin intermediarios, con el dominio citosólico de PERK favoreciendo su trans-autofosforilación. Resultados preliminares indican que, astrocitos CNAβ-/- exhibieron, en condiciones basales, un mayor número de células muertas y de niveles de eIF2α fosforilado que los astrocitos CNAα-/-. Hipótesis: CNAβ/B interacciona con PERK cuando el Ca2+ citosólico esta incrementado luego de haberse inducido Estrés de RE, lo cual promueve dimerización y auto-fosforilación de la quinasa, acentuándose así la fosforilación de eIF2α e inhibición de la síntesis de proteínas. Esta activación citosólica de PERK colaboraría con la ya descrita, desinhibición luminal llevada cabo por BIP. Cuando el Ca2+ citosólico retorna a los niveles basales, PERK fosforila a CN, reduciendo su afinidad de unión y disociándose el complejo CN/PERK. Objetivo general: Definir las condiciones por las cuales CN interacciona con PERK y regula la fosforilación de eIF2α e inhibición de la síntesis de proteína. Objetivos específicos: I-Estudiar la diferencia de afinidades y dependencia de Ca2+, de las dos isoformas de CN (α y β) en su asociación con PERK. Además verificar la posible participación de la subunidad B de CN en esta interacción. II-Determinar si la auto-fosforilación de PERK es diferencialmente regulada por las dos isoformas de CN. III-Discernir la relación del estado de fosforilación de CN con su unión a PERK. IV-Determinar efectos fisiológicos de la interacción de CN-PERK durante la respuesta de Estrés de RE. Para llevar a cabo este proyecto se realizarán experimentos de biología molecular, interacción proteína-proteína, ensayos de fosforilación in vitro y un perfil de polisoma con astrocitos CNAβ-/- , CNA-/- y astrocitos controles. Se espera encontrar una mayor afinidad de unión a PERK de la isoforma β de CN y en condiciones donde la concentración de Ca2+ sea del orden micromolar e imite niveles del ión durante un estrés. Con respecto al estado de fosforilación de CN, debido a los resultados preliminares, donde solo se la encontró fosforilada en condiciones basales, se piensa que CN podría interactuar con mayor afinidad con PERK cuando CN se encuentre desfosforilada. Por último, se espera encontrar un aumento de eIF2α fosforilado y una acentuación de la atenuación de la síntesis de proteína como consecuencia de la mayor activación de PERK por su asociación con la isoforma β de CN en astrocitos donde el Estrés de RE se indujo por privación de oxigeno y glucosa. Estos experimentos permitirán avanzar en el estudio de una nueva función citoprotectora de CN recientemente descrita por nuestro grupo de trabajo y sus implicancias en un modelo de isquemia. The accumulation of unfolded proteins into the Endoplasmic Reticulum (ER) activates a signal transduction cascade called Unfolding Protein Response (UPR), which attempts to restore homeostasis in the organelle. (PKR)-like-ER kinase (PERK) is an early stress response transmembrane protein that is generally inactive due to its association with the chaperone BIP. During ER stress, BIP is tritrated by the unfolded protein, leading PERK activation and phosphorylation of eukaryotic initiation factor-2 alpha (eIF2alpha), which attenuates protein síntesis. If ER damage is too great and homeostasis is not restored within a certain period of time, an apoptotic response is elicited. We recently demonstrated a cytosolic Ca2+ increase in Xenopus oocytes after induce ER stress. Moreover, calcineurin A/B, a an heterotrimeric Ca2+ dependent phosphatases (CN-A/B), associates with PERK increasing its auto-phosphorylation and significantly enhancing cell viability. Preliminary results suggest that, CN-Aβ-/- knockout astrocytes exhibit a significant higher eIF2α phosphorylated level compared to CN-Aα-/- astrocytes. Our working hypothesis establishes that: CN binds to PERK when cytosolic Ca2+ is initially increased by ER stress, promoting dimerization and autophosphorylation, which leads to phosphorylation of elF2α and subsequently attenuation of protein translation. When cytosolic Ca2+ returns to resting levels, PERK phosphorylates CN, reducing its binding affinity so that the CN/PERK complex dissociates. The goal of this project is to determine the conditions by which CN binding to PERK attenuates protein translation during the ER stress response and subsequently, to determine how the interaction of CN with PERK is terminated when stress is removed. To perform this project is planed to do molecular biology experiments, pull down assays, in vitro phosphorylations and assess overall mRNA translation efficiency doing a polisome profile.

Synaptic plasticity in mature cultured hippocampal-entorhinal cortex slices : activity-dependent regulation of cAMP response-element binding protein

LTP, synaptic plasticity, hippocampus, organotypic cultures, CREB

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

Depression as a Clinical Determinant of Dependence and Low Quality of Life in Elderly Patients with Cardiovascular Disease

Background:The aging process promotes a progressive increase in chronic-degenerative diseases. The effect of these diseases on the functional capacity has been well recognized. Another health parameter concerns “quality of life related to health”. Among the elderly population, cardiovascular diseases stand out due to the epidemiological and clinical impact. Usually, these diseases have been associated with others. This set of problems may compromise both independence and quality of life in elderly patients who seek cardiologic treatment. These health parameters have not been well contemplated by cardiologists.Objective:Evaluating, among the elderly population with cardiovascular disease, which are the most relevant clinical determinants regarding dependence and quality of life.Methods:This group was randomly and consecutively selected and four questionnaires were applied: HAQ, SF-36, PRIME-MD e Mini Mental State.Results:The study included 1,020 elderly patients, 63.3% women. The group had been between 60 and 97 years-old (mean: 75.56 ± 6.62 years-old). 61.4% were independent or mild dependence. The quality of life total score was high (HAQ: 88.66 ± 2.68). 87.8% of patients had a SF-36 total score > 66. In the multivariate analysis, the association between diagnoses and high degrees of dependence was significant only for previous stroke (p = 0.014), obesity (p < 0.001), lack of physical activity (p = 0.016), osteoarthritis (p < 0.001), cognitive impairment (p < 0.001), and major depression (p < 0.001). Analyzing the quality of life, major depression and physical illness for depression was significantly associated with all domains of the SF-36.Conclusion:Among an elderly outpatient cardiology population, dependence and quality of life clinical determinants are not cardiovascular comorbidities, especially the depression.

Mortality from Cardiovascular Diseases in the Elderly: Comparative Analysis of Two Five-year Periods

Background:Cardiovascular diseases are the leading cause of death in Brazil. The better understanding of the spatial and temporal distribution of mortality from cardiovascular diseases in the Brazilian elderly population is essential to support more appropriate health actions for each region of the country.Objective:To describe and to compare geospatially the rates of mortality from cardiovascular disease in elderly individuals living in Brazil by gender in two 5-year periods: 1996 to 2000 and 2006 to 2010.Methods:This is an ecological study, for which rates of mortality were obtained from DATASUS and the population rates from the Brazilian Institute of Geography and Statistics (Instituto Brasileiro de Geografia e Estatística). An average mortality rate for cardiovascular disease in elderly by gender was calculated for each period. The spatial autocorrelation was evaluated by TerraView 4.2.0 through global Moran index and the formation of clusters by the index of local Moran-LISA.Results:There was an increase, in the second 5-year period, in the mortality rates in the Northeast and North regions, parallel to a decrease in the South, South-East and Midwest regions. Moreover, there was the formation of clusters with high mortality rates in the second period in Roraima among females, and in Ceará, Pernambuco and Roraima among males.Conclusion:The increase in mortality rates in the North and Northeast regions is probably related to the changing profile of mortality and improvement in the quality of information, a result of the increase in surveillance and health care measures in these regions.

Task-dependent modulation of reward and novelty processing in human ventral striatum and midbrain

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2008