AMPK inhibits voltage-gated calcium channel-current in rat chromaffin cells.

Metabolic changes are critical in the regulation of Ca2+ influx in central and peripheral neuroendocrine cells. To study the regulation of L-type Ca2+ channels by AMPK we used biochemical reagents and ATP/glucose-concentration manipulations in rat chromaffin cells. AICAR and Compound-C, at low concentration, significantly induce changes in L-type Ca2+ channel-current amplitude and voltage dependence. Remarkably, an overlasting decrease in the channel-current density can be induced by lowering the intracellular level of ATP. Accordingly, Ca2+ channel-current density gradually diminishes by decreasing the extracellular glucose concentration. By using immunofluorescence, a decrease in the expression of CaV1.2 is observed while decreasing extracellular glucose, suggesting that AMPK reduces the number of functional Ca2+ channels into the plasma membrane. Together, these results support for the first time the dependence of metabolic changes in the maintenance of Ca2+ channel-current by AMPK. They reveal a key step in Ca2+ influx in secretory cells.

AMPK mediates regulation of voltage-gated calcium channels by leptin in isolated neurons from arcuate nucleus.

Neuronal control of the energy homeostasis requires the arcuate nucleus of the hypothalamus. This structure integrates peripheral and central signals concerning the energy state of the body. It comprises two populations of neurons releasing anorexigenic and orexigenic peptides, among others. Both populations are regulated by leptin, an anorexigenic hormone, released by white adipose tissue. Voltage-gated calcium entry is critical to promote neurotransmitter and hormone release. It is already known that calcium channel current is inhibited by leptin in orexigenic neurons. However, fine-tuning details of calcium channel regulation in arcuate nucleus by leptin remain to be elucidated. This work aimed to investigate whether 5' adenosine monophosphate-activated protein kinase (AMPK) underlies the leptin-induced inhibition of calcium channels. By using patch-clamping methods, immunocytochemical, and biochemical reagents, we recorded calcium channel currents in orexigenic neuropeptide Y neurons of the arcuate nucleus of rats. Consistently, leptin inhibition of the calcium channel current was not only prevented by AMPK inhibition with Compound C but also hampered with 5-aminoimidazole-4-carboxamide ribonucleoside. Furthermore, leptin selectively inhibited L-type calcium channel current amplitude without major changes in voltage dependence or current kinetics. These results support for the first time the key role of AMPK in the maintenance and regulation of voltage-gated calcium channels. Together, they advance our understanding of the regulation of calcium channels in the central nervous system and emerging questions concerning food intake and energy balance.NEW & NOTEWORTHY Our results readily support the hypothesis that AMPK is responsible for the maintenance of the calcium current and mediates the fine-tuning modulation of the leptin response. The novelty of these results strengthens the critical role of AMPK in the general energy balance and homeostasis.

Tecnología y técnicas recomendadas en la irradiación externa del cáncer de mama / Recommended technology and techniques in external radiation of breast cancer

La radioterapia en el cáncer de mama se ha empleado desde hace más de 100 años para el control local de la enfermedad. Las mejoras tecnológicas incorporadas en los últimos 20-30 años han optimizado estos resultados de control local y han conseguido aumentar la supervivencia global (nivel de evidencia 1, en el metaanálisis de Oxford). Realizamos un breve recuerdo histórico de los avances que han cambiado la práctica clínica de la radioterapia en el cáncer de mama, desde las 2 dimensiones a las 3 dimensiones con la incorporación de la tomografía axial computarizada para la simulación virtual, los conceptos de volúmenes de tratamiento, órganos de riesgo, histogramas dosis-volumen y el objetivo de distribución homogénea de la dosis absorbida entre el 95 y el 107%. Las mejoras tecnológicas en las unidades de tratamiento, desde la cobaltoterapia a los aceleradores con multiláminas automáticos con colimación de los haces hasta 5 mm en un tiempo récord, acortando los tiempos de tratamiento y la protección exquisita de los órganos de riesgo, como el pulmón y el corazón. Describiremos las generalidades de las técnicas de radioterapia en el cáncer de mama, la inmovilización en supino y en prono, la posición y volúmenes de tratamiento, la calidad de la radiación, técnica y dosis recomendadas. Mencionaremos también los nuevos fraccionamientos, que están irrumpiendo en la práctica clínica asistencial de la radioterapia del cáncer de mama, con un nivel de evidencia suficiente, con resultados en control local, supervivencia, estéticos y de toxicidad similares a los del fraccionamiento de 2 Gy en 25 fracciones (AU)

Radiation therapy in breast cancer has been used for more than a century for local disease control. Improved technology in the last 20-30 years has maximized outcomes not only in achieving local control but also in increasing overall survival (level 1 evidence in an Oxford meta-analysis). We present a brief historical review of all the technical and scientific advances that have changed clinical practice in breast cancer radiotherapy. These include the switch from 2-dimensional to 3-dimensional technology with the use of computed tomography for virtual simulation, the new concepts of treatment volumes, organs at risk and dose-volume histograms, and the objective of a homogeneous distribution of the absorbed dose of between 95% and 107%. Technological advances in treatment units, from cobalt therapy to accelerators with MLC leaves with beam collimation of up to 5 mm in record time have shortened treatment times and provide exquisite protection to at-risk organs, such as the heart or lung. We describe the general features of radiation therapy techniques in breast cancer, including immobilization in supine and prone positions, the position and volumes of treatment, the quality of radiation, the technique, and recommended doses. We also mention the new dose fractions that are breaking into the clinical practice of breast cancer radiotherapy, with a considerable level of evidence showing good results in terms of local control, survival rates, and esthetic outcomes, as well as toxic effects very similar to those achieved with the standard dose of 50 Gy in 25 fractions of 2 Gy (AU)

Operational stability to changes in composition of herbicide mixtures fed to a laboratory-scale biobarrier.

The main objective of this work was to evaluate the operational stability of a laboratory-scale aerobic biobarrier designed for the treatment of water contaminated by mixtures of three herbicides frequently found in agricultural runoffs, atrazine, simazine and 2,4-dichlorophenoxyacetic acid (2,4-D). The microbial consortium used to degrade the herbicides was composed by six cultivable bacterial strains, identified as members of the genera Variovorax, Sphingopyxis, Hydrocarboniphaga, Methylobacterium, Pseudomonas and Acinetobacter. The effect caused by a seventh member of the microbial consortium, a ciliated protozoa of the genus Colpoda, on the herbicides biodegradation kinetics, was also evaluated. The biodegradation of five combinations of the herbicides 2,4-D, atrazine and simazine was studied in the biobarrier, operated in steady state continuous culture at different volumetric loading rates. In all cases, removal efficiencies determined by chemical oxygen demand (COD) and HPLC were nearly 100 %. These results, joined to the null accumulation of aromatic byproducts of atrazine and simazine catabolism, show that after 495 days of operation, in the presence of the protozoa, the adaptability of the microbial consortium to changing environmental conditions allowed the complete removal of the mixture of herbicides.

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population.

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation.

Shock hemorrágico secundario a sangrado por diverticulosis yeyunal / Hemorrhagic shock secondary to bleeding due to jejunal diverticulosis

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Peritonitis bacteriana espontánea secundaria a Enterobacter cloacae / No disponible

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Neumonía y síndrome coronario agudo con elevación de ST: una asociación infrecuente / Association of acute respiratory symptoms with the onset of acute myocardial infarction

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Neumonia comunitaria grave por Chlamydia pneumoniae / Severe community pneumonia by Chlamydia

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Neumonía y síndrome coronario agudo con elevación de ST: una asociación infrecuente / Pneumonia and ST elevated acute coronary syndrome

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Plexopatía braquial secundaria a venopunción subclavia para implante de marcapasos definitivo / Brachial plexopathy secondary to subclavian venopuncture for implant of final pacemakers

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[Type III glycogen storage disease associated with hepatocellular carcinoma]. / Glucogenosis tipo III asociada a carcinoma hepatocelular.

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma.

Glucogenosis tipo III asociada a carcinoma hepatocelular / Type III glycogen storage disease associated with hepatocellular carcinoma

La glucogenosis hepática tipo III es una enfermedad hereditaria que se transmite de forma autosómica recesiva. Se caracteriza por la acumulación de glucógeno anormal en el hígado y, en el 80% de los pacientes, en el músculo. En el hígado pueden observarse fibrosis y, a veces, cirrosis hepática. Hasta el año 2000 se habían publicado 9 casos de cirrosis, 3 con hepatocarcinoma asociado. Se presenta el caso de una mujer de 31 años, diagnosticada en la infancia de glucogenosis tipo III, que a los 30 años de evolución desarrolló un carcinoma hepatocelular con trombosis portal sobre una cirrosis avanzada. Es el primero en la bibliografía española de glucogenosis tipo III asociada a carcinoma hepatocelular

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma

Síndrome coronario agudo como complicación de enfermedad inflamatorio intestinal / Coronary acute syndrome like complication on inflammatory intestinal disease

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Obstrucción de la vía aérea superior secundaria a edema faringolaríngeo por hematoma cervical / Obstruction of upper airway because of pharyngeal-laryngeal edema by cervical hematoma

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Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension.

High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-alpha), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-alpha, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP >or=140 and/or diastolic BP >or=90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P=0.003), third (PR: 2.32; P=0.031), and fourth quartiles (PR: 2.30; P=0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-alpha levels were 1.41 (P=0.014) for the second; 1.59 (P=0.001) for the third; and 1.61 (P=0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-alpha and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.

Afectación del sistema nervioso central en intoxicación aguda por carbamatos / Central nervous system involvement in acute carbamate intoxication

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Hematoma suprarrenal unilateral espontáneo / Spontaneous unilateral adrenal haematoma

La aparición de hematomas suprarrenales espontáneos en el adulto es un hecho excepcional, aún más si son de localización unilateral, siendo habitualmente el diagnóstico post-mortem. Aunque aparentemente puede ocurrir sin relación con factores predisponentes. Existen más descripciones de hematomas secundarios a diversas patologías. Se describe un caso de un hematoma suprarrenal unilateral espontáneo, revisando los factores etiológicos relacionados con el desarrollo de esta afección sus manifestaciones clínicas y diagnóstico (AU)