RESUMEN
Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.
Asunto(s)
Neoplasias Abdominales/rehabilitación , Neoplasias Abdominales/cirugía , Terapia por Ejercicio/métodos , Tolerancia al Ejercicio , Evaluación de Programas y Proyectos de Salud/métodos , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Resultado del TratamientoRESUMEN
An educational device was created to develop a hands-on activity to illustrate how atherosclerosis can dramatically reduce blood flow in human vessels. The device was conceived, designed, and built at the University of Coimbra, in response to a request from the Exploratório Infante D. Henrique Science Centre Museum, where it is presently installed. The device was designed to allow lay audience to operate it, including school-age youngsters. The two blood flow reduction mechanisms that can be visualized are 1) thickening of the artery wall and 2) hardening of the artery wall. The main objective is to promote the understanding of atherosclerotic cardiovascular physiology by simple and direct experiments. This original educational interactive device was constructed using, in the conceptual and design stages of the project, a Newtonian theoretical flow model based on Poiseuille's equation. This device is driven by human force and provides a visualization of the effect of atherosclerosis on flow. The main aspects relating to its design and construction are described here to explain and disseminate this approach. Throughout more than 4 yr of real operation, this educational device proved to be a simple and attractive way of understanding atherosclerosis, especially among young people.
Asunto(s)
Aterosclerosis/fisiopatología , Circulación Sanguínea , Equipos y Suministros , Vasos Sanguíneos/fisiopatología , Adaptabilidad , Humanos , Fisiología/educación , PortugalRESUMEN
BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.
Asunto(s)
Enfermedad Crítica/mortalidad , Neoplasias/mortalidad , Neoplasias/fisiopatología , Equilibrio Hidroelectrolítico/fisiología , APACHE , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/fisiopatología , Anciano , Área Bajo la Curva , Femenino , Humanos , Intubación Intratraqueal , Tiempo de Internación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/mortalidad , Insuficiencia Multiorgánica/fisiopatología , Valor Predictivo de las Pruebas , Respiración Artificial , Choque Séptico/etiología , Choque Séptico/fisiopatología , Sobrevida , Resultado del Tratamiento , Vasoconstrictores/uso terapéuticoRESUMEN
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease in which much burden is geared towards end-of-life care. Particularly in the earlier stages of ALS, many people have found both physiological and psychological boosts from various types of physical exercise for disused muscles. Proper exercise is important for preventing atrophy of muscles from disuse-a key for remaining mobile for as long as possible-and as long as it is possible to exercise comfortably and safely, for preserving cardiovascular fitness. However, the typical neuromuscular patient features a great physical inactivity and disuse weakness, and for that reason many controversial authors have contested exercise in these patients during years, especially in ALS which is rapidly progressive. There is an urgent need for dissecting in detail the real risks or benefits of exercise in controlled clinical trials to demystify this ancient paradigm. Yet, recent research studies document significant benefits in terms of survival and quality of life in ALS, poor cooperation, small sample size, uncontrolled and short-duration trials, remain the main handicaps. Sedentary barriers such as early fatigue and inherent muscle misuse should be overcome, for instance with body-weight supporting systems or non-invasive ventilation, and exercise should be faced as a potential non-monotonous way for contributing to better health-related quality of life.
Asunto(s)
Esclerosis Amiotrófica Lateral/rehabilitación , Terapia por Ejercicio/psicología , Ejercicio Físico/fisiología , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/psicología , Ejercicio Físico/psicología , HumanosRESUMEN
Recent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the erythrocyte deformability was determined. The present study shows that in the presence of higher fibrinogen concentrations, similar to those found in inflammatory conditions, erythrocyte deformability is increased only when band 3 is dephosphorylated by the presence of syk inhibitor and at low shear stress. On the contrary, no changes were verified in the presence of fibrinogen when band 3 is allowed to be phosphorylated by inhibiting the phosphotyrosine phosphatase enzyme activity with calpeptin. We also observed that the presence of fibrinogen at higher concentration does not induce changes in erythrocyte deformability in the absence of modulators of the band 3 phosphorylation degree. However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study.
Asunto(s)
Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Enfermedades Cardiovasculares/sangre , Membrana Eritrocítica/metabolismo , Fibrinógeno/metabolismo , Deformación Eritrocítica , Eritrocitos/metabolismo , Humanos , Masculino , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas/sangre , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/sangre , Transducción de SeñalRESUMEN
The erythrocytes ability of sensing the local oxygen gradient through the hemoglobin conformation, along with changes in nitric oxide mobilization and vasomotor repercussions at the microcirculation, were reviewed in detail in this article. Different approachs trying to explain the erythrocyte death were additionally documented. Also, the influence of several types of molecules (vasoactive, oxidant/reductor) on the erythrocyte roles as sensor of (i) oxygen tissue needs, (ii) blood viscosity and myogenic environment, (iii) and inflammatory conditions were mentioned in order to highlight its physiologycal function and substitute the erroneous idea of the erythrocyte being simply a hemoglobin sac content.
Asunto(s)
Biomarcadores/metabolismo , Eritrocitos/fisiología , Proteína 1 de Intercambio de Anión de Eritrocito/metabolismo , Viscosidad Sanguínea , Permeabilidad de la Membrana Celular/fisiología , Supervivencia Celular , Membrana Eritrocítica/fisiología , Eritrocitos/metabolismo , Hemoglobinas/metabolismo , Humanos , Inflamación/fisiopatología , Síndrome Metabólico/sangre , Microcirculación , Óxido Nítrico/metabolismo , Oxígeno/sangre , Oxígeno/metabolismo , VasodilataciónRESUMEN
Recent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present pioneer in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Hyperfibrinogenemia interferes with erythrocyte NO mobilization without changing its efflux in a way that seems to be dependent of the degree of band 3 phosphorylation. In presence of higher fibrinogen concentrations the NO efflux is reinforced when band 3 is phosphorylated (p < 0.001). Higher levels of nitrite, nitrate and GSNO were documented (p < 0.05). However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study. These conditions may be considered an approach to be followed in blood storage for transfusions.
Asunto(s)
Proteína 1 de Intercambio de Anión de Eritrocito/fisiología , Eritrocitos/metabolismo , Fibrinógeno/fisiología , Óxido Nítrico/sangre , Procesamiento Proteico-Postraduccional , Proteína 1 de Intercambio de Anión de Eritrocito/química , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Difusión , Dipéptidos/farmacología , Membrana Eritrocítica/metabolismo , Eritrocitos/efectos de los fármacos , Fibrinógeno/análisis , Flavonoides/farmacología , Genisteína/análogos & derivados , Glutatión/análogos & derivados , Glutatión/farmacología , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Masculino , Nitratos/sangre , Nitritos/sangre , Nitrocompuestos/farmacología , Concentración Osmolar , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinasa SykRESUMEN
We review the major hemorheological experimental studies that show the erythrocyte aggregation as a link between basic and clinical research. The results of the clinical cross-sectional and longitudinal studies presented here will highlight the possible association between erythrocyte aggregation and plasma fibrinogen. Basic studies conducted in vitro are also mentioned as for its relevance in answering questions raised in clinical settings, as well as and in understanding the underlying influent factors in the erythrocyte tendency to aggregate and disaggregate.
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Agregación Eritrocitaria , Hematología , Investigación , Enfermedades Cardiovasculares/sangre , Estudios Transversales , Agregación Eritrocitaria/efectos de los fármacos , Femenino , Fibrinógeno/análisis , Fibrinógeno/farmacología , Glaucoma/sangre , Humanos , Hipercolesterolemia/sangre , Hipertensión Inducida en el Embarazo/sangre , Enfermedades Renales/sangre , Estudios Longitudinales , Masculino , Estudios Multicéntricos como Asunto , Óxido Nítrico/sangre , EmbarazoRESUMEN
In the present article the authors make an approach over the applications of dithiothreitol (DTT) in its different clinical-laboratory, potential and up-to-date sources. Dithiothreitol is a chemical reagent with a wide actuation spectrum not only from a laboratorial view but also from a therapeutic standpoint, more clinical and practical. DTT (i) is frequently used in a variety of experiences that involve proteins or peptides, protecting sulfhydryl groups from oxidation and reducing disulfide bonds between cysteines; (ii) is also used in the study of disulfide exchange reactions of protein disulfides; (iii) is able to keep glutathione in the reduced state; (iv) acts as an "antidote" enabling the activity of detoxification systems; (v) participates in cellular mechanisms such as vesiculation, cell morphology, signal transduction pathways (hormone-'like' role), etc.; (vi) can be used in the treatment approach of diseases like cystinosis or medical conditions resulting from ion or metal toxicity. In erythrocytes, there's literature pointing that DTT may trigger changes on the normal discoid shape following metabolic depletion, and additionally modulate the exovesiculation kinetics as demonstrated by us. The present article dissects in detail recent findings in our Unit concerning the DTT influence on human erythrocytes.
Asunto(s)
Ditiotreitol/metabolismo , Eritrocitos/metabolismo , Sustancias Reductoras/metabolismo , Animales , Eritrocitos/citología , HumanosRESUMEN
Acetylcholine is well known in the medical setting as one of the most exemplary neurotransmitters. Its ubiquity in nature otherwise suggests a theoretically diverse spectrum of action and an extremely early appearance in the evolutionary process. In humans, acetylcholine and its synthesizing enzyme, choline acetyltransferase, have been found in various nonneural tissues such as the epithelium, mesothelium, endothelium, muscle, immune cells and blood cells. The widespread expression of nonneuronal acetylcholine is accompanied by the ubiquitous presence of acetylcholinesterase and nicotinic/muscarinic receptors. Structural and functional dissimilarities are evident between the nonneuronal and neuronal cholinergic systems. An increasing body of evidence throughout the last few years has placed acetylcholine as a major cellular signaling molecule in many pathways. Furthermore, numerous erythrocyte physiological events in the microcirculation are strongly regulated by acetylcholine. Thus, it is time to revise our understanding of the role of vascular acetylcholine in humans. Its biological and pathobiological roles must be evaluated in more detail to eventually achieve novel therapeutical targets. The present article reviews recent findings about nonneuronal acetylcholine in red blood cells, with special regard to (1) red cell rheology, (2) plasma ion concentrations, (3) nitric oxide intracellular translocation and metabolism and (4) band 3 protein phosphorylation.
Asunto(s)
Acetilcolina/metabolismo , Eritrocitos/metabolismo , Acetilcolinesterasa/metabolismo , Humanos , Modelos Biológicos , Óxido Nítrico/metabolismo , Receptores Muscarínicos/metabolismoRESUMEN
Experimental evidence has shown that plasma fibrinogen plays a key role as a major cardiovascular risk factor, acting directly to trigger erythrocyte aggregation in occlusive vascular disease. However, due to the complex and hitherto unclear interaction between fibrinogen and the erythrocyte membrane, no study has yet evaluated the effects of fibrinogen, under physiological range values, on the erythrocyte nitric oxide (NO) mobilization. Taking into consideration the potential NO-derived molecules, we have raised the hypothesis that fibrinogen, under physiological conditions, may act to influence blood flow via erythrocyte NO modulation. In this in vitro study whole-blood samples were harvested from healthy subjects, erythrocyte suspensions were incubated in the absence (control aliquots) and presence of different fibrinogen concentrations and levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Our results showed, when compared with control aliquots, that the presence of fibrinogen modulates the NO mobilization in erythrocytes by (1) decreasing erythrocyte NO efflux levels (P < 0.001); (2) increasing levels of intraerythrocytic NO oxidative metabolites, namely, nitrite (P < 0.0001) and nitrate (P < 0.0001); and (3) enhancing the formation of GSNO (P < 0.001). In conclusion, this study provides new insights into an unknown mechanism by which fibrinogen modulates the erythrocyte capacity to supply NO, the effects of which on inflammation profiles (generally associated with blood hyperviscosity and hyperaggregation) still need to be elucidated. Also, increased erythrocyte GSNO levels may be associated with platelet NO metabolism, its activation status and hypotension, which may be extremely relevant in the clinical setting as biomarkers.
Asunto(s)
Eritrocitos/metabolismo , Fibrinógeno/fisiología , Óxido Nítrico/sangre , Agregación Eritrocitaria/efectos de los fármacos , Membrana Eritrocítica/fisiología , Eritrocitos/efectos de los fármacos , Glutatión/análogos & derivados , Glutatión/farmacología , Humanos , Masculino , Nitratos/farmacología , Nitritos/farmacología , Nitrocompuestos/farmacología , S-Nitrosoglutatión/metabolismo , Transducción de SeñalRESUMEN
Circulating acetylcholine, substrate of membrane acetylcholinesterase (AChE), is known to enhance the band 3 protein degree of phosphorylation. The purpose of this study was to verify whether the band 3 phosphorylation status is associated with a G protein and whether it is an influent factor on AChE enzyme activity. From blood samples of healthy donors, erythrocyte suspensions were prepared and incubated with AChE substrate (acetylcholine) and inhibitor (velnacrine), along with protein tyrosine kinase (PTK) and tyrosine phosphatase (PTP) inhibitors. AChE activity was determined by spectrophotometry and extract samples were analyzed by western blotting using primary antibodies to different G protein subunits. Our results with phosphorylated band 3 (PTP inhibitor) show an increase in erythrocyte AChE (p < 0.0001). A dephosphorylated band 3 state (PTK inhibitor) shows a significant decrease. We identified a potential linkage of protein subunits Galpha(i1/2) and G(beta) with band 3 protein. Galpha(i1/2) and G(beta) may be linked to the band 3 C-terminal site. Galpha(i1/2) is associated with the band 3 N-terminal domain, except for the control and ACh aliquots. G(beta) is associated with both phosphorylated and dephosphorylated band 3 in the presence of velnacrine. We conclude that an erythrocyte G protein with subunits Galpha(i1/2) and G(beta) is associated with band 3. AChE depends on the degree of band 3 phosphorylation and its association with Galpha(i1/2) and G(beta).