RESUMEN
OBJECTIVE: The main purpose of this study was to characterize the determinants of metabolic changes in young type 1 diabetes (T1DM) and to determine glycemic variability during low and high-intensity exercise. PATIENTS AND METHODS: 20 young male T1DM patients were divided into two subgroups characterized by levels of glycated hemoglobin (HbA1c): HbA1c<7.3% (better HbA1c subgroup, n=10) and with levels HbA1c>7.3% (worse HbA1c subgroup, n=10). All participants performed a maximal oxygen uptake test and two efforts of various intensities (45 minutes of aerobic exercise and 30 minutes of mixed aerobic-anaerobic intensity exercise). Continuous glucose monitors (CGM) were used to control the glucose concentration. RESULTS: Changes in biomarkers describing the metabolic response were similar in both groups. A comparison of applied efforts exhibited that maximal capacity effort resulted in the highest values of blood glucose (BG) at the end (150.9-160.6 mg/dl) and 1 hour after the exercise (140.2-161.3 mg/dl). BG concentration before, during, 1 hour, and 24 hours after each exercise was insignificantly higher in the worse Hb1Ac group. CONCLUSIONS: HbA1c levels are insufficient to confirm whether the applied effort is performed in acceptable glycemic values. The CGM monitors allow for precise control of BG variations and accurate planning of physical activity by adjusting the insulin and carbohydrate consumption dose.
Asunto(s)
Diabetes Mellitus Tipo 1 , Glucosa , Humanos , Adolescente , Masculino , Hemoglobina Glucada , Glucemia , Ejercicio FísicoRESUMEN
In this article, computation for the purpose of spatial visualization is presented in the context of understanding the variability in global environmental processes. Here, we generate synthetic but realistic global data sets and input them into computational algorithms that have a visualization capability; we call this a simulation-visualization system. Visualization is key here, because the algorithms which we are evaluating must respect the spatial structure of the input. We modify, augment, and integrate four existing component technologies: statistical conditional simulation, Discrete Global Grids (DGGs), Array Set Addressing, and a visualization platform for displaying our results on a globe. The internal representation of the data to be visualized is built around the need for efficient storage and computation as well as the need to move up and downresolutions in a mutually consistent way. In effect, we have constructed a Geographic Information System that is based on a DGG and has desirable data storage, computation, and visualization capabilities. We provide an example of how our simulation-visualization system may be used, by evaluating a computational algorithm called Spatial Statistical Data Fusion that was developed for use on big, remote-sensing data sets.
RESUMEN
Excessive nitrogen runoff leads to degraded water quality, harming human and ecosystem health. We examine the impact of changes in land use and land management for six combinations of socioeconomic pathways and climate outcomes, and find that societal choices will substantially impact riverine total nitrogen loading (+54% to -7%) for the continental United States by the end of the century. Regional impacts will be even larger. Increased loading is possible for both high emission and low emission pathways, due to increased food and biofuel demand, respectively. Some pathways, however, suggest that limiting climate change and eutrophication can be achieved concurrently. Precipitation changes will further exacerbate loading, resulting in a net increase of 1 to 68%. Globally, increases in cropland area and agricultural intensification will likely impact vast portions of Asia. Societal and climate trends must therefore both be considered in designing strategies for managing inland and coastal water quality.
Asunto(s)
Eutrofización , Agricultura/tendencias , Asia , Cambio Climático , Ecosistema , Humanos , Modelos Teóricos , Nitrógeno/análisis , Ríos/química , Medio Social , Factores Socioeconómicos , Estados Unidos , Tiempo (Meteorología)RESUMEN
Addiction is a chronic psychiatric disease which represents a global problem, and stress can increase drug addiction and relapse. Taking into account frequent concomitance of nicotine dependence and stress, the purpose of the present study was to assess behavioral and biochemical effects of chronic unpredictable mild stress (CUMS) exposure on nicotine reward in rats measured in the conditioned place preference (CPP) paradigm. Rats were submitted to the CUMS for 3 weeks and conditioned with nicotine (0.175 mg/kg) for 2 or 3 days. Our results revealed that only CUMS-exposed animals exhibited the CPP after 2 days of conditioning indicating that stressed rats were more sensitive to the rewarding properties of nicotine and that chronic stress exacerbates nicotine preference. Administration of metyrapone (50 mg/kg), a glucocorticosteroid antagonist, and imipramine (15 mg/kg), an antidepressant, abolished nicotine CPP in stressed rats after 2 days of conditioning. The biochemical experiments showed increased markers of oxidative stress after nicotine conditioning for 2 and 3 days, while the CUMS further potentiated pro-oxidative effects of nicotine. Moreover, metyrapone reversed oxidative changes caused by stress and nicotine, while imipramine was not able to overwhelm nicotine- and stress-induced oxidative damages; however, it could exert antioxidant effect if administered repeatedly. The results suggest that recent exposure to a stressor may augment the rewarding effects of nicotine through anhedonia- and stress-related mechanisms. Our study contributes to the understanding of behavioral and biochemical stress-induced modification of the rewarding effects of nicotine on the basis of the development of nicotine dependence.
Asunto(s)
Conducta Animal , Conducta de Elección , Condicionamiento Clásico , Estrés Psicológico/complicaciones , Tabaquismo/etiología , Animales , Enfermedad Crónica , Imipramina/farmacología , Masculino , Metirapona/farmacología , Actividad Motora/efectos de los fármacos , Nicotina , Estrés Oxidativo/efectos de los fármacos , Ratas WistarRESUMEN
Eutrophication, or excessive nutrient enrichment, threatens water resources across the globe. We show that climate change-induced precipitation changes alone will substantially increase (19 ± 14%) riverine total nitrogen loading within the continental United States by the end of the century for the "business-as-usual" scenario. The impacts, driven by projected increases in both total and extreme precipitation, will be especially strong for the Northeast and the corn belt of the United States. Offsetting this increase would require a 33 ± 24% reduction in nitrogen inputs, representing a massive management challenge. Globally, changes in precipitation are especially likely to also exacerbate eutrophication in India, China, and Southeast Asia. It is therefore imperative that water quality management strategies account for the impact of projected future changes in precipitation on nitrogen loading.
Asunto(s)
Cambio Climático , Eutrofización , Nitrógeno , Contaminación Química del Agua , Calidad del Agua , Asia Sudoriental , China , Humanos , India , Lluvia , Estados UnidosRESUMEN
Nicotine, the main component of tobacco smoke, exerts influence on mood, and contributes to physical and psychological dependence. Taking into account frequent concomitance of nicotine abuse and stress, we aimed to research behavioral and biochemical effects associated with nicotine administration in combination with chronic unpredictable mild stress (CUMS). Mice were submitted to the procedure of CUMS for 4 weeks, 2 h per day. Our results revealed that CUMS-exposed animals exhibited behavioral alteration like anxiety disorders in the elevated plus maze (EPM) test, the disturbances in memory in the passive avoidance (PA) test and depressive effects in the forced swim test (FST). Moreover, nicotine (0.05-0.5 mg/kg), after an acute or subchronic administration decreased stress-induced depression- and anxiety-like effect as well as memory deficit. Administration of metyrapone (50 mg/kg), a glucocorticosteroid antagonist, alleviated the depressive effect induced by the CUMS. The biochemical experiments showed decreased values of the total antioxidant status (TAS), activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) with simultaneously increased in malondialdehyde (MDA) concentration in mice submitted to the CUMS. The same effects were observed after an acute and subchronic nicotine administration within all examined brain structures (i.e., hippocampus, cortex, and cerebellum) and in the whole brain in non-stressed and stressed mice confirming pro-oxidative effect of nicotine. Our study contributes to the understanding of behavioral and biochemical mechanisms involved in stress-induced disorders such as depression, anxiety and memory disturbances as well as dual nicotine-stress interactions on the basis of the development of nicotine dependence.
Asunto(s)
Reacción de Prevención/fisiología , Encéfalo/metabolismo , Aprendizaje por Laberinto/fisiología , Nicotina/toxicidad , Estrés Oxidativo/fisiología , Estrés Psicológico/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Encéfalo/efectos de los fármacos , Enfermedad Crónica , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Agonistas Nicotínicos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Estrés Psicológico/inducido químicamente , Estrés Psicológico/psicologíaRESUMEN
Terrestrial ecosystems play a vital role in regulating the accumulation of carbon (C) in the atmosphere. Understanding the factors controlling land C uptake is critical for reducing uncertainties in projections of future climate. The relative importance of changing climate, rising atmospheric CO2, and other factors, however, remains unclear despite decades of research. Here, we use an ensemble of land models to show that models disagree on the primary driver of cumulative C uptake for 85% of vegetated land area. Disagreement is largest in model sensitivity to rising atmospheric CO2 which shows almost twice the variability in cumulative land uptake since 1901 (1 s.d. of 212.8 PgC vs. 138.5 PgC, respectively). We find that variability in CO2 and temperature sensitivity is attributable, in part, to their compensatory effects on C uptake, whereby comparable estimates of C uptake can arise by invoking different sensitivities to key environmental conditions. Conversely, divergent estimates of C uptake can occur despite being based on the same environmental sensitivities. Together, these findings imply an important limitation to the predictability of C cycling and climate under unprecedented environmental conditions. We suggest that the carbon modeling community prioritize a probabilistic multi-model approach to generate more robust C cycle projections.
RESUMEN
It has been suggested that alterations of serotonin transport may be implicated in the pathogenesis of the neuropsychiatric symptoms encountered in acute liver failure. In order to address this issue, microdialysate concentrations of serotonin, its precursor L-tryptophan and metabolite 5-hydroxyindoleacetic acid (5-HIAA) as well as brain regional distribution of serotonin transporter ([3H]-citalopram) sites were measured in rats with acute liver failure resulting from hepatic devascularization. A significant loss of [3H]-citalopram sites was observed in dorsal Raphe nucleus, in frontal and frontoparietal cortices as well as in substantia nigra of rats with severe encephalopathy resulting from acute liver failure. In frontal cortex, this loss of transporter binding sites was accompanied by significant increases of L-tryptophan, serotonin and 5-HIAA concentrations in extracellular fluid. Pharmacological manipulation of the brain serotonin system could afford a novel therapeutic approach to the prevention of the neuropsychiatric symptoms characteristic of acute liver failure in humans.
Asunto(s)
Fallo Hepático/metabolismo , Glicoproteínas de Membrana/deficiencia , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso , Enfermedad Aguda , Animales , Sitios de Unión , Proteínas Portadoras , Citalopram/metabolismo , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Ácido Hidroxiindolacético/metabolismo , Isquemia/complicaciones , Circulación Hepática , Masculino , Ratas , Ratas Sprague-Dawley , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Distribución Tisular , Triptófano/metabolismoRESUMEN
There is increasing evidence that central noradrenaline (NA) transport mechanisms are implicated in the central nervous system complications of acute liver failure. In order to assess this possibility, binding sites for the high affinity NA transporter ligand [3H]-nisoxetine were measured by quantitative receptor autoradiography in the brains of rats with acute liver failure resulting from hepatic devascularization and in appropriate controls. In vivo microdialysis was used to measure extracellular brain concentrations of NA. Severe encephalopathy resulted in a significant loss of [3H]-nisoxetine sites in frontal cortex and a concomitant increase in extracellular brain concentrations of NA in rats with acute liver failure. A loss of transporter sites was also observed in thalamus of rats with acute liver failure. This loss of NA transporter sites could result from depletion of central NA stores due to a reserpine-like effect of ammonia which is known to accumulate to millimolar concentrations in brain in ischemic liver failure. Impaired NA transport and the consequent increase in synaptic concentrations and increased stimulation of neuronal and astrocytic noradrenergic receptors could be implicated in the pathogenesis of the encephalopathy and brain edema characteristic of acute liver failure.
Asunto(s)
Proteínas Portadoras/metabolismo , Lóbulo Frontal/metabolismo , Encefalopatía Hepática/metabolismo , Isquemia/complicaciones , Fallo Hepático/complicaciones , Hígado/irrigación sanguínea , Proteínas del Tejido Nervioso/deficiencia , Simportadores , Enfermedad Aguda , Amoníaco/metabolismo , Animales , Edema Encefálico/etiología , Edema Encefálico/metabolismo , Fluoxetina/análogos & derivados , Fluoxetina/metabolismo , Encefalopatía Hepática/etiología , Masculino , Proteínas del Tejido Nervioso/metabolismo , Norepinefrina/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática , Derivación Portocava Quirúrgica , Ratas , Ratas Sprague-Dawley , Tálamo/metabolismoRESUMEN
It has been suggested that reduced astrocytic uptake of neuronally released glutamate contributes to the pathogenesis of hepatic encephalopathy in acute liver failure. In order to further address this issue, the recently cloned and sequenced astrocytic glutamate transporter GLT-1 was studied in brain preparations from rats with ischemic liver failure induced by portacaval anastomosis followed 24 h later by hepatic artery ligation and from appropriate sham-operated controls. GLT-1 expression was studied using reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of GLT-1 transcript was significantly decreased in frontal cortex at coma stages of acute liver failure. Western blotting using a polyclonal antibody to GLT-1 revealed a concomitant decrease in expression of transporter protein in the brains of rats with acute liver failure. Reduced capacity of astrocytes to reuptake neuronally released glutamate, resulting from a GLT-1 transporter deficit and the consequently compromised neuron-astrocytic trafficking of glutamate could contribute to the pathogenesis of hepatic encephalopathy and brain edema, two major complications of acute liver failure.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Lóbulo Frontal/metabolismo , Fallo Hepático Agudo/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Sistema de Transporte de Aminoácidos X-AG , Animales , Astrocitos/metabolismo , Western Blotting , Lóbulo Frontal/química , Expresión Génica/fisiología , Encefalopatía Hepática/etiología , Encefalopatía Hepática/metabolismo , Encefalopatía Hepática/fisiopatología , Fallo Hepático Agudo/complicaciones , Masculino , Neuronas/metabolismo , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of the present study, was to establish the hepatic profile of acyl-coenzyme A (acyl-CoA) in relation to the hepatic profile of acylcarnitines in chronically hyperammonemic spf mice (hereditary deficiency in ornithine transcarbamylase) treated with sodium benzoate alone or in combination with L-carnitine. The muscular profile of the acylcarnitines and the stability of sarcolemma were also assessed in the same mice. Following administration of sodium benzoate, we observed decreases in hepatic total and free coenzyme A and in acetyl-CoA, which was accompanied by an increase in hepatic acyl-CoA. This treatment also resulted in increased free carnitine, decreased total carnitine, and decreased short and medium chain acylcarnitines in the liver. Increases in plasma creatine kinase levels, muscular free, total, and in short and medium chain acylcarnitines were also observed in this treatment group. In mice receiving a combination of sodium benzoate and L-carnitine, increases in free and total coenzyme A, acetyl-CoA and in free, total and esterified hepatic carnitines were observed. In this treatment group, the plasma level of creatine kinase was found to be reduced, while the free muscular carnitine was increased. Our results indicate that sodium benzoate is implicated in the decrease of total hepatic coenzyme A, through either an inhibition of CoA synthesis or activation of its degradation. The distribution of hepatic coenzyme-A and of hepatic and muscular carnitine (free or esterified) is altered following administration of sodium benzoate which results in a further destabilization of the sarcolemma induced by hyperammonemia. Supplemental treatment with L-carnitine was shown to have a positive effect by increasing hepatic coenzyme A and carnitine levels and restoring the stability of the sarcolemma caused by the treatment of sodium benzoate alone.
Asunto(s)
Acetilcarnitina/análisis , Acilcoenzima A/análisis , Amoníaco/sangre , Benzoatos/farmacología , Carnitina/farmacología , Conservantes de Alimentos/farmacología , Animales , Benzoatos/administración & dosificación , Ácido Benzoico , Carnitina/administración & dosificación , Enfermedad Crónica , Creatina Quinasa/sangre , Quimioterapia Combinada , Conservantes de Alimentos/administración & dosificación , Hígado/química , Ratones , Ratones Mutantes , Músculo Esquelético/químicaRESUMEN
Sodium benzoate is conjugated with glycine in the liver and the kidney, which may cause the elimination of one mole of alpha-amino N for each mole of benzoate administered. However, muscle does not possess the enzyme activity to form benzoylglycine. The object of this study was to identify the secondary effects of acute sodium benzoate treatment on the concentrations of carnitine in liver and muscle when the glycine availability in these tissues is still assured. Our studies are based on chronically hyperammonemic spf/Y mice with a deficiency of ornithine transcarbamylase. The animals were given 2.5, 5.0 and 10.0 mmol/kg sodium benzoate intraperitoneally. Control groups of normal mice received identical treatments. Our results demonstrate that sodium benzoate influences the homeostasis of liver and muscle carnitine after only 15 minutes of treatment. We observed a reduction of short- and medium-chain acylcarnitines in the liver of normal mice, and an increase of free carnitine and long-chain acylcarnitines in the spf mice. In muscle, we found a reduction of free carnitine and short- and medium-chain acylcarnitines at doses of 5.0-10.0 mmol benzoate/kg in the normal mice. However, we observed a significant reduction of long-chain acylcarnitines in muscle tissue from spf mice. The carnitine concentrations in each tissue differ depending on the dose of sodium benzoate administered, which may suggest a biphasic effect. Our results indicate that sodium benzoate has a secondary effect on the liver and muscle concentration of carnitine from the beginning of its intramitochondrial metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Amoníaco/sangre , Benzoatos/farmacología , Carnitina/análisis , Hígado/química , Músculos/química , Acetilcarnitina/análisis , Animales , Benzoatos/uso terapéutico , Ácido Benzoico , Relación Dosis-Respuesta a Droga , Hígado/efectos de los fármacos , Masculino , Ratones , Ratones Mutantes , Músculos/efectos de los fármacosRESUMEN
In the years 1975-1989 26 children were treated in hospital for acute leukaemia, who fell ill before completion of the second year of life. The analysis carried out similarly, as in the reports of other authors, showed worse results of treatment of leukaemia in this group of children.
Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Femenino , Humanos , Lactante , Masculino , Pronóstico , Resultado del TratamientoRESUMEN
Allergic reactions of dramatic intensity were observed in 5 children treated with Teniposide (VM-26) for acute lymphoblastic leukaemia and histiocytosis X. In the further treatment this drug was replaced with epoxide, a cytostatic agent which is also a podophyllin derivative but in other chemical formulation. In none of these patients the allergic reaction returned.
Asunto(s)
Hipersensibilidad a las Drogas/etiología , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tenipósido/efectos adversos , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
The clinical course and effects of treatment of congenital spherocytosis (CS) were analyzed in 28 children. In 10 cases the disease ran a severe clinical course. Jaundice, anaemia, and splenomegaly were the most frequent clinical signs which were significantly intensified during haemolytic crises. In 14 cases splenectomy was performed, obtaining in all children a regression of jaundice and anaemia. Before the operation two children were vaccinated with Pneumo 23. In asplenic children Debecillin was prophylactically used. Serious infectious complications were observed only in one patient.
Asunto(s)
Esferocitosis Hereditaria/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Penicilina G Benzatina/uso terapéutico , Premedicación , Esferocitosis Hereditaria/diagnóstico , Esplenectomía , VacunaciónRESUMEN
Erythematous changes of the palms with associated oedema, blistering and desquamation were observed in two children during chemotherapy for acute lymphoblastic leukaemia, after methotrexate in doses of 1,000 mg/m2. These changes correspondent to those described in the literature as Burgdorf's reaction. In Poland it was never reported as yet.
Asunto(s)
Eritema/inducido químicamente , Dermatosis de la Mano/inducido químicamente , Metotrexato/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Intravenosas , Masculino , Metotrexato/administración & dosificación , Dolor/inducido químicamenteRESUMEN
In a 7-year-old child Lyell's syndrome was observed with extensive bullous epidermal necrolysis with a very severe clinical course. The disease could have been explained as a toxic-allergic reaction to sefril and aspirin taken for pharyngitis.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Aspirina/efectos adversos , Cefradina/efectos adversos , Faringitis/tratamiento farmacológico , Síndrome de Stevens-Johnson/etiología , Antiinflamatorios no Esteroideos/administración & dosificación , Aspirina/administración & dosificación , Cefradina/administración & dosificación , Niño , Terapia Combinada , Quimioterapia Combinada , Humanos , Masculino , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/terapiaRESUMEN
A clinical analysis was carried out of the course of the disseminated form of the disease in 20 children aged from one month to 8 years (mean age 11 months). Unfavourable prognostic significance was confirmed of such factors as: child's age at the time of falling ill lower than two years, number of the involved organs and their dysfunction, and lacking reaction to treatment during the first three months of the disease.
Asunto(s)
Histiocitosis de Células de Langerhans/terapia , Niño , Preescolar , Femenino , Histiocitosis de Células de Langerhans/diagnóstico , Humanos , Lactante , Masculino , Pronóstico , Factores de RiesgoRESUMEN
Concentrations of MTX were determined in the cerebrospinal fluid (csf) and serum after intravenous infusion of MTX at intermediate dose (0.5-1.0 g/m2) and at high dose (5.0 g/m2) to 20 children (33 infusions) with ALL/NHL. The cytotoxic concentrations of MTX in csf (> 1.0 microM/l) were reached in half of the cases after the infusion of MTX at intermediate dose and in all patients after the infusion of 5.0 g/m2. Great inpatient and interpatient variations of MTX concentrations in csf were observed. No statistically significant difference was found between mean systemic clearance of MTX in patients with MTXcsf concentrations > 1.0 microM/l and < 1.0 microM/l after infusion of MTX at intermediate dose.
Asunto(s)
Linfoma no Hodgkin/tratamiento farmacológico , Metotrexato/líquido cefalorraquídeo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Humanos , Infusiones Intravenosas , Linfoma no Hodgkin/líquido cefalorraquídeo , Metotrexato/administración & dosificación , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquídeo , Factores de TiempoRESUMEN
A girl with acute myelogenous leukemia (AML) was treated with high dose arabinoside cytosine during consolidation. She developed jaundice twice after the completion of 3 rd and 4 th cycle of the drug. The jaundice was characterized by conjugated hyperbilirubinemia, elevated aminotransferases and alkaline phosphatase. The histologic study of the liver showed only infiltration by mononuclear cells in portal space and scarce bile pigment in some hepatocytes. In both cases jaundice receded spontaneously. Now the patient has been in complete remission for 36 months and subsequent liver function tests are normal.