RESUMEN
Water storage plays an important role in mitigating heat and flooding in urban areas. Assessment of the water storage capacity of cities remains challenging due to the inherent heterogeneity of the urban surface. Traditionally, effective storage has been estimated from runoff. Here, we present a novel approach to estimate effective water storage capacity from recession rates of observed evaporation during precipitation-free periods. We test this approach for cities at neighborhood scale with eddy-covariance based latent heat flux observations from 14 contrasting sites with different local climate zones, vegetation cover and characteristics, and climates. Based on analysis of 583 drydowns, we find storage capacities to vary between 1.3 and 28.4 mm, corresponding to e-folding timescales of 1.8-20.1 days. This makes the urban storage capacity at least five times smaller than all the observed values for natural ecosystems, reflecting an evaporation regime characterized by extreme water limitation.
RESUMEN
BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin combined with docetaxel as first-line treatment of advanced ACC. METHODS: Patients with advanced ACC were included in this phase II trial investigating the response to a combination of cisplatin (50 mg m(-2)) and docetaxel (60 mg m(-2)) administered with a 3-week interval. RESULTS: Nineteen patients were included in this study. The response rate was 21% (95% CI: 3-39%). No patients obtained a complete response, 32% had stable disease, and 37% progressed while on treatment. The median progression-free survival (PFS) was 3 months (95% CI: 0.7-5.3 months) and 1 year PFS was 21% (95% CI: 3-39%). Median survival was 12.5 months (95% CI: 6-19 months). The predominant grade 3/4 toxicity was neutropenia (35%); febrile neutropenia occurred in 5% of cycles. CONCLUSION: This study could not demonstrate that the combination of cisplatin and docetaxel has higher efficacy than other regimens reported in previous studies.
Asunto(s)
Neoplasias de la Corteza Suprarrenal/tratamiento farmacológico , Carcinoma Corticosuprarrenal/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Taxoides/administración & dosificación , Neoplasias de la Corteza Suprarrenal/mortalidad , Neoplasias de la Corteza Suprarrenal/patología , Carcinoma Corticosuprarrenal/mortalidad , Carcinoma Corticosuprarrenal/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Progresión de la Enfermedad , Docetaxel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Taxoides/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
This review discusses laboratory and clinical studies of antisense oligodeoxynucleotides as potential treatments for haematological malignancies and solid tumours. Mechanisms of action, pharmacokinetics, toxicities and potential clinical applications of these agents are described.
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Neoplasias/tratamiento farmacológico , Oligonucleótidos Antisentido/uso terapéutico , Apoptosis , Transporte Biológico , Resistencia a Múltiples Medicamentos , Humanos , Oligonucleótidos Antisentido/efectos adversos , Oligonucleótidos Antisentido/farmacocinética , Oncogenes/genéticaRESUMEN
The effect of aminoguanidine (AG) on the production of superoxide anion O2*- and nitric oxide (NO) by peripheral blood granulocytes of rats with streptozotocin-induced diabetes was studied. Induction of diabetes resulted in an increase of O2*-. Generation by both unstimulated and opsonized zymosan-stimulated granulocytes was maximal after 6 weeks and lower after 12 weeks. Treatment with aminoguanidine (1 g/l drinking water) decreased O2*- generation after 6 weeks but not after 12 weeks. NO production by both unstimulated and opsonized zymosan-stimulated granulocytes was elevated in diabetic rats to a comparable extent after 6 and 12 weeks. AG attenuated this increased NO production. These results point to the beneficial effect of AG on oxidative stress in experimental diabetes and suggest an antioxidant effect of AG.
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Diabetes Mellitus Experimental/sangre , Granulocitos/efectos de los fármacos , Guanidinas/farmacología , Óxido Nítrico/biosíntesis , Superóxidos/sangre , Animales , Aniones , Glucemia/metabolismo , Peso Corporal , Hemoglobina Glucada/metabolismo , Granulocitos/metabolismo , Masculino , Óxido Nítrico/sangre , Ratas , Ratas Wistar , EstreptozocinaRESUMEN
Cardiac ischemia/reperfusion leads to coronary endothelial dysfunction, mediated by superoxide anion (O2-), but not hydroxyl radical (*OH). Ischemic preconditioning and mitochondrial ATP-dependent potassium channel opener (diazoxide) protect endothelium in the mechanism involving attenuation of O2- burst at reperfusion. We hypothesize that the endothelial protection involves upregulation of myocardial anty-O2- defense. Langendorff-perfused guinea-pig hearts were subjected to global ischemia/reperfusion (IR) or were preconditioned prior to IR with three cycles of ischemia/reperfusion (IPC) or infusion/washout of 0.5 microM diazoxide. Coronary flow responses to acetylcholine were measures of endothelium-dependent vascular function. Myocardial outflow of O2- and of *OH during reperfusion and myocardial activities of superoxide dismutase (SOD) and catalase were measured. IR impaired acetylcholine response and augmented cardiac O2- and *OH outflow. IPC, diazoxide, and SOD (150 IU/ml) attenuated O2- outflow, increased *OH outflow and protected endothelium. There were no differences in Cu/Zn-SOD, Mn-SOD and catalase activities between sham-perfused and IR hearts and only catalase activity was increased in the IPC hearts. We speculate that: (i) IPC and diazoxide endothelial protection involves activation of some SOD-like anti-O2- mechanism resulting in attenuation of O2- burst and increase in *OH burst, (ii) improved SOD activity might have not been detected because it was confined to a small, although functionally important, enzyme fraction, like that bound to the endothelial glycocalyx.
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Diazóxido/farmacología , Endotelio Vascular/efectos de los fármacos , Precondicionamiento Isquémico Miocárdico , Sustancias Protectoras/farmacología , Animales , Catalasa/metabolismo , Endotelio Vascular/enzimología , Endotelio Vascular/metabolismo , Glicocálix/metabolismo , Cobayas , Radical Hidroxilo/metabolismo , Técnicas In Vitro , Miocardio/enzimología , Miocardio/metabolismo , Superóxido Dismutasa/metabolismo , Superóxidos/metabolismoRESUMEN
This paper describes how ultrasonic images of the female breast have been processed and neural nets used to aid the identification of malignant and benign areas in them. The images are windowed, filtered and pre-processed into suitable patterns for processing by a neural net. Two networks are trained and used: one for malignant cases and the other for benign cases. These are used to make predictions of regions of interest which are presented as circles overlaid on the image. The system has been prototyped and tested and experts agreed well with the classification and localisation. The system is usually weak when the evidence on the image is considered weak by the expert. It is concluded that the system is promising and should be developed further by providing more training to the network.
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Neoplasias de la Mama/diagnóstico por imagen , Diagnóstico por Computador , Redes Neurales de la Computación , Femenino , Humanos , Ultrasonografía/métodosRESUMEN
This paper investigates the factors relevant to producing effective human factors design guidance, using the Engineering Data Compendium (EDC) as a research vehicle. A series of three exploratory experiments focusing on the factors that affect the usability, usefulness and viability of human factors handbooks was conducted. The results of these studies were interpreted in the context of the process by which the EDC was developed, leading to the following recommendations: (a) human factors guidance should be organized in a manner that is stepped in context; (b) human factors guidance should be based on an explicit requirements analysis; (c) the calibration of designers' perceptions of the cost of obtaining human factors information must be improved; (d) organizational policies must be changed to induce more effective information search behaviour.
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Ergonomía/métodos , Guías como Asunto , Manuales como Asunto , Análisis de Varianza , Humanos , Almacenamiento y Recuperación de la Información , Transferencia de TecnologíaRESUMEN
Results of surgical treatment of 182 patients with pleural empyema were assessed. Patients were divided into 2 groups according to the length of time between the beginning of illness and the start of treatment at the thoracosurgical department. The first group consisted of 36 patients in whom the draining of empyema's chamber was applied no later than 7 days after the onset of illness. This treatment was effective in 31 (86%) of patients. The remaining, 14% of patients required operative treatment. The second group consisted of 146 patients who were admitted to surgical department later than 7 days from the beginning of disease. 33% of them required operative treatment. The results achieved in both groups of patients proved that the time lapse between, the beginning of disease and the confirmation of suppurative character of exudation, had a decisive influence on the surgical procedure and the final results of treatment.
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Empiema Pleural/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Diabetes is known to involve oxidative stress. However, data on oxidative stress in diabetic nephropathy is scant. The aim of this study was to examine lipid peroxidation and activities of key antioxidant enzymes in non-insulin dependent diabetes (NIDDM) without nephropathy and in those with diabetic nephropathy. METHODS: Twenty-one NIDDM outpatients with obvious diabetic nephropathy (persistent proteinuria, over 0.5 g/day and albumin excretion over 200 microg/min), 14 NIDDM outpatients with a long diabetic history but without hypertension and with normal urinary albumin excretion rate (<20 microg/min) and 19 healthy persons were studied. Malondialdehyde (MDA) content of erythrocytes was quantified by HPLC according to Young et al. In erythrocytes, superoxide dismutase (SOD) activity was determined by the adrenaline method of Misra and Fridovich and catalase was estimated according to Beers and Sizer. RESULTS: MDA content was significantly elevated in erythrocytes of NIDDM patients without nephropathy vs the control group and even higher in erythrocytes of NIDDM patients with diabetic nephropathy. SOD and catalase activities were lower in erythrocytes of NIDDM patients without nephropathy than in the control group and lowest in erythrocytes of NIDDM patients with nephropathy. CONCLUSIONS: These results confirm oxidative stress in erythrocytes of NIDDM patients with nephropathy. The intensity of oxidative stress appeared to be greater than in NIDDM patients without nephropathy.
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Catalasa/sangre , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/metabolismo , Eritrocitos/metabolismo , Peroxidación de Lípido , Superóxido Dismutasa/sangre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The effect of aminoguanidine (AG) on the malondialdehyde (MDA) concentration and activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in erythrocytes of rats with streptozotocin-induced diabetes was studied. Induction of diabetes resulted in an increase of MDA concentration and decreases of SOD and catalase activities after 6 and 12 weeks. GSH-Px activity increased after 6 weeks and returned to control values after 12 weeks. AG administration did not affect body weight, blood glucose level and HbA1c content in diabetic rats but led to a decrease of MDA concentration and SOD and catalase activities after 12 weeks of treatment, with no significant effect after 6 weeks. AG attenuated the GSH-Px increase after 6 weeks but augmented the activity of this enzyme after 12 weeks. These results confirm the presence of oxidative stress in streptozotocin-induced experimental diabetes and point to the beneficial antioxidant effect of AG.
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Diabetes Mellitus Experimental/sangre , Eritrocitos/efectos de los fármacos , Guanidinas/farmacología , Peroxidación de Lípido/efectos de los fármacos , Animales , Glucemia/análisis , Peso Corporal , Catalasa/sangre , Diabetes Mellitus Experimental/enzimología , Eritrocitos/enzimología , Eritrocitos/metabolismo , Glutatión Peroxidasa/sangre , Hemoglobina Glucada/metabolismo , Malondialdehído/sangre , Ratas , Ratas Wistar , Estreptozocina , Superóxido Dismutasa/sangreRESUMEN
Phagocytes (granulocytes and macrophages) are one of the most important sources of reactive oxygen species (ROS) in the human body. A stimulated phagocyte reaches within a dozen of seconds the functional state known as the respiratory burst. This phenomenon includes three interrelated processes: 1) a several fold increase in the oxygen uptake, 2) generation of large amounts of ROS, and 3) stimulations of glucose metabolism via the pentose phosphate shunt. The main ROS generated during phagocytosis is the superoxide radical anion O2-. The reaction of dismutation of O2- generates hydrogen peroxide (H2O2). O2- and H2O2 do not have strong cytocidal proerties but are supbstrates for the generation of more active biologically ROS, especially the hydroxyl radical (OH) and hypochlorous acid (HOCl). A stimulated phagocyte (especially neutrophil) generates also vast amounts of nitric oxide (NO-). NO- may react with the superoxide radical anion forming peroxynitrate (ONOO-). Reactivity of ONOO- is comparable to that of the hydroxyl radical. ONOO- plays probably a very important role in the so-called oxygen-dependent killing mechanisms during phagocytosis. The role of NO- in the process of phagocytosis is unclear. However, NO-, apart from other biological functions, inhibits aggregation and adhesion of blood platelets. Morevover, it seems to participate in the slefregulation of granulocyte cativity (probably limiting excessive inflammative reaction). Excess of ROS generated by phagocytes may damage biologically important macromolecules. Membrane lipids are particularly vulnerable to peroxidation. It leads to alterations in membrane fluidity and permeability. ROS excreted to the environment of a phagocyte may impair functions of other morphotic elements of blood (erythrocytes and thromobcytes) in this way. Bed rest covers two conditions: 1) limitation of motoric activity (hypodynamia) and 2) restraining the pressure on bones along parallelly to their long axes (hypogravia). Under bed rest conditions organism is subject to many harmful changes. I.a., bed rest affects also leukocyte functions. However, we were not aware of any sutdies concerning the effect of bed rest on the respiratory burst of granulocytes. This study was aimed at an examination of the effect of bed rest on the generation of O; and H2O2 by neutrophils (PMNL).
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Reposo en Cama , Neutrófilos/fisiología , Óxido Nítrico/metabolismo , Oxígeno/metabolismo , Adulto , Traumatismos del Brazo , Radicales Libres , Humanos , Peróxido de Hidrógeno , Inmovilización , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Oxígeno/sangre , Especies Reactivas de OxígenoRESUMEN
Bed rest is an integral part of treatment of numerous diseases. Typical examples are bone fractures of lower extremities and pelvis. Temporary immobilization is necessary also, e.g., in heart diseases (stroke), backbone and imminent abortion. The sick organism spares energy during the bed rest wich is beneficial. However, bed rest results in many alterations which are disadavantageous. They concern the function of almost all organs and systems but affect most significantly the locomotor and ciruclatory systems. Bed rest brings also about changes in the composition of peripheral blood and functions of the morphotic elements of blood. Red blood cells are subjected to the action of large amounts of reactive oxygen species (ROS). During oxidation of hemoglobin to methemoglobin superoxide radical anion (O2-) is formed: HbFe2+ + O2 --> MetHbFe3+ + O2- (1) Ferrous and ferric ions present in the cytoplasm of red blood cells may be catalysts of the Fenton reaction leading to the production of the hydroxyl radical: O2- + Fe3+ --> O2- + Fe2+ (2) Fe2+ + H2O2 --> Fe3+ + OH + HO- (3) OH shows a tremendous reactivity. It may react with lipids, proteins, nucleic acids and carbohydrates. The process of lipid peroxidation is best understood. It concerns mainly polyunsaturated fatty acids present in cell membranes. Peroxidation of membrane lipids decreases membrane fluidity and impairs its barrier function. The lowered membrane fluidity compromises erythrocyte deormability which in turn disturbs oxygen delivery to the tissues. End productions of lipid peroxidation are low-molecular wieght compounds, among them carbohydrates (ethane and pentane) and aldehydes, e.g. malondialdehyde (MDA). MDA concentration is an acknowldeged marker of the intensity of lipid peroxidation. Erythrocytes contain a complex system of protection against the action of ROS. It includes various enzymatic and non-enzymatic mechanism. The most important antioxidative enzymes of the red blood cells are superoxide dismutase (Cu,Zn-SOD, EC 1.15.1.1) catalase (CAT, EC 1.11.1.6) and glutathione peroxidase (GSH-Px, EC 1.11.1.9). Cu,Zn-SOD catalyzes the dismuation of O2- to hydrogen peroxide (H2O2). Catalase and peroxidase remove H2O2 and, moreover, GSH-Px can reduce lipid peroxides. Under normal conditions an equilibrium exists between the formation and removal ROS. If ROS are formed in excess or the defensive antioxidative mechanism are inefficient, oxidative stress develops. Derangement of the equilibrium between the formation and removal of ROS is important in the pathosgenesis of many diseases, e.g. atherosclerosis, diabetes, Down syndrome and Alzheimer disease. There are literature data on disturbances of enzymatic antioxidant defense mechanism of blood plateless during bed rest. This study was aimed at an examination of the post-traumatic bed rest on the enzymatic antioxidative defense mechanisms and lipid peroxidation in erythrocytes.