Remdesivir plus dexamethasone is associated to improvement in the clinical outcome of COVID-19 hospitalized patients regardless of their vaccination status / Remdesivir más dexametasona se asocian a una reducción de los eventos clínicos en los pacientes hospitalizados por COVID-19, independientemente de su estado de vacunación

Introduction Remdesivir seems to reduce the risk of hospitalization and improve clinical outcome in hospitalized patients with COVID-19. Objectives To compare the clinical outcome of COVID-19 hospitalized patients treated with remdesivir plus dexamethasone versus dexamethasone alone, according to their vaccination status. Material and methods A retrospective observational study was carried out in 165 patients hospitalized for COVID-19 from October 2021 to January 2022. Multivariate logistic regression, Kaplan–Meier and the log-rank tests were used to evaluate the event (need for ventilation or death). Results Patients treated with remdesivir plus dexamethasone (n=87) compared with dexamethasone alone (n=78) showed similar age (60±16, 47–70 vs. 62±37, 51–74 years) and number of comorbidities: 1 (0–2) versus 1.5 (1–3). Among 73 fully vaccinated patients, 42 (47.1%) were in remdesivir plus dexamethasone and 31 (41%) in dexamethasone alone. Patients treated with remdesivir plus dexamethasone needed intensive care less frequently (17.2% vs. 31%; p=0.002), high-flow oxygen (25.3% vs. 50.0%; p=0.002) and non-invasive mechanical ventilation (16.1% vs. 47.4%; p<0.001). Furthermore, they had less complications during hospitalization (31.0% vs. 52.6%; p=0.008), need of antibiotics (32.2% vs. 59%; p=0.001) and radiologic worsening (21.8% vs. 44.9%; p=0.005). Treatment with remdesivir plus dexamethasone (aHR, 0.26; 95% CI: 0.14–0.48; p<0.001) and vaccination (aHR 0.39; 95% CI: 0.21–0.74) were independent factors associated with lower progression to mechanical ventilation or death. Conclusions Remdesivir in combination with dexamethasone and vaccination independently and synergistically protects hospitalized COVID-19 patients requiring oxygen therapy from progression to severe disease or dead (AU)

Introducción Remdesivir parece reducir el riesgo de hospitalización y mejorar el resultado clínico en pacientes hospitalizados con COVID-19. Objetivos Comparar el desenlace clínico de pacientes hospitalizados con COVID-19 tratados con remdesivir más dexametasona vs. dexametasona sola, según su estado de vacunación. Material y métodos Se realizó un estudio observacional retrospectivo en 165 pacientes hospitalizados por COVID-19 desde octubre de 2021 hasta enero de 2022. Se consideró como evento la necesidad de ventilación o muerte. esultados Los pacientes tratados con remdesivir más dexametasona (n=87) en comparación con dexametasona sola (n=78) mostraron una edad similar (60±16, 47-70 vs. 62±37, 51-74 años) y número de comorbilidades: 1 (0-2) vs. 1,5 (1-3). Entre 73 pacientes completamente vacunados, 42 (47,1%) estaban en remdesivir más dexametasona y 31 (41%) en dexametasona sola. Los pacientes tratados con remdesivir más dexametasona necesitaron cuidados intensivos con menos frecuencia (17,2 vs. 31%; p=0,002), oxígeno de alto flujo (25,3 vs. 50%; p=0,002) y ventilación mecánica no invasiva (16,1 vs. 47,4%, p<0,001). Además, tuvieron menos complicaciones durante la hospitalización (31 vs. 52,6%; p=0,008), necesidad de antibióticos (32,2 vs. 59%; p=0,001) y empeoramiento radiológico (21,8 vs. 44,9%; p=0,005). El tratamiento con remdesivir más dexametasona (aHR, 0,26; IC 95% 0,14-0,48; p<0,001) y la vacunación (aHR 0,39; IC 95% 0,21-0,74>) fueron factores independientes asociados con una menor progresión a ventilación mecánica o muerte. Conclusiones Remdesivir en combinación con dexametasona protegieron de forma independiente y sinérgica a los pacientes hospitalizados con COVID-19 que requieren oxigenoterapia de la progresión a la enfermedad grave o la muerte (AU)

Publicaciones sobre hidroxicloroquina y remdesivir: actualización septiembre 2020 / Hydroxicloroquine and remdesivir publications: update September 2020

El debate científico sobre las terapéuticas eficaces y seguras para tratar la Covid-19 desde su comienzo en enero 2020 ha dado lugar a miles de publicaciones con sus implicaciones sociales y económicas respecto a fabricantes farmacéuticos, investigadores clínicos y publicaciones científicas. En este nuevo comentario se resumen las publicaciones de junio a septiembre de 2020 sobre los dos medicamentos más contrapuestos en muchos ámbitos clínicos: hidroxicloroquina y remdesivir

The scientific debate about the effective and safe therapies to treat the COVID-19 from its beginning in January 2020 has led to thousands of publications with their social and economic implications related to pharmaceutical manufacturers, clinical researchers and scientific publications. In this new comment, there are summarized the publications from June to September, 2020 about the two more opposing medications in many clinical settings: hydroxychloroquine and remdesivir

Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation

The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently (AU)

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Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women

Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1â. When compared to NGT pregnant women, AMPKá activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKá. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1â-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1â as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance

Effects of treadmill running and rutin on lipolytic signaling pathways and TRPV4 protein expression in the adipose tissue of diet-induced obese mice

To explore the effects of rutin and exercise on high-fat diet (HFD)-induced disrupted lipolytic signaling, adenosine 5Œ-monophosphate (AMP)-activated protein kinase (AMPK) signaling, transient receptor potential cation channel subfamily V member 4 (TRPV4) and its associated protein expression, and whether depot-specific effects existed. C57BL/6J mice were randomized into five groups: chow group, HFD, HFD plus rutin intervention group (HR), HFD combined with treadmill running group (HE), and HFD combined with treadmill running and rutin intervention group (HRE). At the end of the 16-week intervention, lipolytic markers, AMPK signaling pathways, TRPV4, and peroxisome proliferator-activated receptor gamma coactivator 1Alpha + Beta (PGC-1Alpha + Beta) from adipose tissue were measured by western blotting. In epididymal adipose tissue, HFD resulted in significant reduction in the phosphorylation of hormone sensitive lipase at serine660 (p-HSL660), perilipin A, phosphoenolpyruvate carboxykinase (PEPCK), p-AMPK, and p-acetyl-CoA carboxylase (ACC) protein expression. Exercise intervention and exercise plus rutin completely restored p-HSL660, perilipin A, PEPCK, p-AMPK, and p-ACC protein expression to normal level. HFD and HR groups have reduced expression of PGC-1Alpha + Beta, exercise, and exercise plus rutin completely restored PGC-1Alpha + Beta expression to normal level. In subcutaneous adipose tissue, HFD elevated TRPV4, exercise, and exercise plus rutin completely reduced TRPV4 to normal level. HR, HE, and HRE group have increased PGC-1Alpha + Beta. In conclusion, depot-specific effects existed in regards to how rutin and exercise affect lipolytic signaling and p-AMPK, as well as TRPV4 and PGC-1Alpha + Beta expression

Aspectos metabólicos e nutricionais do magnésio / Metabolic and nutritional aspects of magnesium

Estudos atuais têm mostrado inadequação na ingestão de diversos nutrientes, sendo o magnésio, em particular, um mineral com consumo reduzido pela população. Considerando a importância do magnésio no metabolismo e manutenção da homeostase do organismo, a escassez de dados sobre o consumo desse mineral, esta revisão visa trazer informações atualizadas sobre o metabolismo, biodisponibilidade e ingestão desse micronutriente. Foi conduzida uma revisão narrativa, sendo que o levantamento bibliográfico foi realizado nas bases de dados PubMed, SciELO, Lilacs, utilizando as seguintes palavras-chave: 'magnesium metabolism', 'bioavailability', 'intake'. A deficiência de magnésio pode decorrer da ingestão inadequada ou excreção aumentada, sendo a homeostase desse nutriente, em nosso organismo, regulada principalmente pelos rins. Existem fatores inibidores do processo de absorção do magnésio, como a presença na dieta de alimentos ricos em fitatos, oxalatos, fosfatos e fibras alimentares; e promotores, tais como a lactose e carboidratos. Observa-se que a ingestão média de magnésio pela população encontra-se em valores inferiores às recomendações das Dietary Reference Intakes. Assim, é evidente a existência de inadequação no consumo de magnésio, o que contribui para a manifestação de sua deficiência na população, sendo necessários estudos sobre o tema, considerando que o metabolismo desse mineral não está completamente elucidado, bem como suas interações com outros nutrientes ou substâncias da dieta (AU)

Recent studies have shown inadequate intake of various nutrients, and magnesium, in particular is a mineral with reduced consumption among the population. Therefore, considering the importance of magnesium metabolism in maintenance of homeostasis, the paucity of data regarding the consumption of this mineral, this review aims to bring current information on metabolism, bioavailability and intake of this micronutrient. A narrative review was conducted, and the literature was carried out in the databases PubMed, SciELO, Lilacs, using the following key words: 'magnesium metabolism', 'bioavailability', 'intake'. Magnesium deficiency can result from inadequate intake or increased excretion, and the homeostasis of this nutrient in our body is mainly regulated by the kidneys. There are factors that inhibit the absorption process of magnesium, such as the presence in the diet of foods rich in phytates, oxalates, phosphates and dietary fiber; and promoters, such as lactose, and carbohydrates. It is observed that the average intake values of magnesium by the population are lower than recommendations of the Dietary Reference Intakes. Thus, it is clear that there is inadequacy in magnesium consumption, which contributes to manifestation of their disability in the population, and studies on the topic are required, whereas the metabolism of this mineral is not fully elucidated, neither their interactions with other nutrients or dietary substances (AU)

Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle

AIM: The aim of this study was to compare the effects and mechanisms of action of metformin on estrogen receptor (ER)-positive and ER-negative breast cancer cell lines. METHODS: The anti-proliferative effects of metformin, and of the direct activator of adenosine monophosphate-activated protein kinase (AMPK), A-769662, on MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) breast cancer cell lines were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, a yellow tetrazole) assays. Fluorescence-activated cell sorting was also used to examine the effect of metformin on the cell cycle. Finally, phosphorylation of the metformin target AMPK, and of its potential downstream targets including acetyl-CoA carboxylase (ACC), p53, p70-S6K and Raptor, was examined using immunoblotting. RESULTS: Metformin and A-769662 caused significant, concentration-dependent suppression of cell proliferation with G1 cell cycle arrest in both MCF-7 and MDA-MB-231 cells. The proliferation suppression effect was more profound in MCF-7 cells. A concentration-dependent phosphorylation of AMPK was detected following metformin treatment, as was phosphorylation of ACC in both cell lines, but not p53, p70-S6k or Raptor. CONCLUSION: Metformin acts as a growth inhibitor in both ER-positive and ER-negative breast cancer cells in vitro, and arrests cells in G1 phase, particularly in the ER-positive MCF-7 cells. The effect is likely to be mediated by AMPK activation, in part by inhibition of fatty acid synthesis via ACC phosphorylation (AU)

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Predictive Value of the Response to Inhaled Adenosine 5'-Monophosphate for Reducing the Dose of Inhaled Corticosteroids in Asthma

Antecedentes: En los pacientes asmáticos bien controlados, las guías recomiendan reducir las dosis de esteroides inhalados. No obstante, no existe ningún tipo de información acerca de qué determinaciones pudieran utilizarse para predecir el éxito o fracaso de esta estrategia terapéutica. Objetivo: Investigar la utilidad de la determinación de la respuesta bronquial a AMP para predecir la evolución del asma tras reducir la dosis de esteroides inhalados. Pacientes y métodos: Se estudiaron 70 pacientes asmáticos bien controlados con esteroides inhalados. Durante las primeras 2 semanas, los pacientes fueron tratados con sus dosis habituales de esteroides inhalados, para a continuación y durante las 12 semanas siguientes recibir tratamiento con la mitad de la dosis de estos fármacos indicada basalmente. Se realizaron estudios de la respuesta bronquial a AMP, tanto basalmente como al cabo de dos semanas de reducir la dosis de esteroides inhalados. Las curvas concentración-respuesta se caracterizaron mediante la concentración de agonista que inducía una caída del FEV1 del 20% (PC20). Resultados: La identificación de una reducción de la PC20 AMP de al menos una concentración doble, 2 semanas después de reducir la dosis de esteroides inhalados, podía predecir el riesgo de exacerbación del asma como consecuencia de la disminución de la dosis de la medicación controladora (P=0.0011). Por el contrario, la determinación de la respuesta basal a AMP no tenía capacidad predictiva significativa. Conclusiones: Los resultados del estudio sugieren que, en pacientes asmáticos bien controlados con esteroides inhalados, la identificación de las modificaciones de la respuesta a AMP al cabo de 2 semanas de reducir la dosis de esteroides inhalados a la mitad permite evaluar el riesgo de futuras exacerbaciones de la enfermedad (AU)

Background: Guidelines recommend stepping down inhaled corticosteroids (ICS) in patients with well-controlled asthma. However, no information is available on the index that should be used to predict the outcome of reducing the ICS dose. Objective: The aim of this study was to investigate the degree of airway responsiveness to adenosine 5’ monophosphate (AMP) as an index for deciding whether to reduce ICS dose. Patients and Methods: The study population comprised 70 patients with asthma that was well controlled with ICS. Patients were treated for a 2-week baseline period with their usual dose of ICS. For the following 12 weeks, patients were treated with ICS at half their previous dose. Bronchial challenge with AMP was performed at the end of the baseline period and after 2 weeks of treatment with a reduced dose of ICS. Concentration-response curves were used to show the provocative concentration of AMP causing a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). Results: A decrease in the PC20 of AMP of at least 1 doubling concentration 2 weeks after reducing the ICS dose was a significant predictor of the failure of dose reduction (P=.0011). In contrast, increased responsiveness to inhaled AMP at baseline did not predict the failure of dose reduction. Conclusions: Our results suggest that, in patients whose asthma is well controlled with ICS, measurement of the modification in the response to AMP 2 weeks after the dose of ICS was halved is a suitable method for assessing the risk of asthma exacerbation following a reduction in ICS dose (AU)

La activación de PPARβ/δ previene la hipertrigliceridemia causada por una dieta rica en grasas. Implicación de la AMPK y de la vía PGC-1α-lipina 1-PPAR / PPARβ/δ Activation prevents hypertriglyceridemia caused by a high fat diet. Involvement of AMPK and PGC-1α-Lipin 1-PPARα pathway

Introducción El consumo excesivo de alimentos hipercalóricos y de alto contenido en grasas saturadas produce una dislipidemia aterogénica. En este estudio hemos analizado los efectos del activador de PPARβ/δ GW501516 sobre la hipertrigliceridemia inducida por una dieta rica en grasas. Metodología Ratones macho fueron distribuidos aleatoriamente en 3 grupos: control (dieta estándar), dieta grasa (high fat diet [HFD], 35% grasa en peso, 58% kcal procedentes de grasa) y dieta grasa más GW501516 (3 mg/kg/día). La duración del tratamiento fue de 3 semanas. Resultados La HFD causó hipertrigliceridemia acompañada de una reducción de los niveles hepáticos de la proteína AMPK fosforilada y de los niveles de ARNm Pgc-1α y lipina 1. Estos efectos fueron revertidos por el tratamiento con GW501516. El mantenimiento de la AMPK fosforilada tras el tratamiento con GW501516 podría deberse al aumento de la relación AMP/ATP. GW501516 incrementó los niveles de proteína lipina 1 nuclear acompañado por una amplificación de la vía PGC-1α-PPARα y un aumento de la actividad de unión al ADN de PPARα, así como el incremento en la expresión de los genes diana de PPARα implicados en la β-oxidación de ácidos grasos. GW501516 también aumentó los niveles plasmáticos de β-hidroxibutirato, producto final de la β-oxidación hepática. Finalmente, GW501516 incrementó los niveles del ligando endógeno de PPARα, 16:0/18:1-fosfatidilcolina, y aumentó la expresión del receptor de las VLDL en hígado. Conclusión El efecto hipotrigliceridemiante de GW501516 en ratones sometidos a HFD se acompaña de un aumento de los niveles de la AMPK fosforilada y de un aumento de la vía PGC-1α-lipina 1-PPARα (AU)

Introduction Excessive consume of hypercaloric and high in saturated fat food causes an atherogenic dyslipidemia. In this study we analyzed the effects of PPARβ/δ activator GW501516 on the hypertriglyceridemia induced by a high-fat diet. Methods Male mice were randomized in three groups: control (standard chow), high fat diet (HFD, 35% fat by weight, 58% Kcal from fat) and high fat diet plus GW501516 (3 mg/Kg/day). Treatment duration was three weeks. Results HFD-induced hypertriglyceridemia was accompanied by a reduction in hepatic levels of phospho-AMPK and in PGC-1α and Lipin 1 mRNA levels. All these effects were reversed by GW501516 treatment. The lack of changes in phospho-AMPK levels after GW501516 treatment in HFD-fed animals could be the result of an increase in the AMP/ATP ratio. GW501516 treatment also increased Lipin 1 protein levels in the nucleus, led to the amplification of the PGC-1α-PPARα pathway and increased PPARα DNA-binding activity, as well as the expression of PPARα-target genes involved in fatty acid oxidation. GW501516 also increased β-hydroxibutirate plasmatic levels, a hepatic β-oxidation end product. Finally, GW501516 increased the hepatic levels of the PPARα endogenous ligand 16:0/18:1-PC and the expression of the VLDL receptor. Conclusion These data indicate that the hypotriglyceridemic effect of GW501516 in mice subjected to HFD-fed mice is accompanied by an increase in phospho-AMPK levels and the amplification of the PGC-1α-Lipin 1-PPARα pathway (AU)

Diabetes, mitocondrias y ejercicio / Diabetes, mitochondria and exercise

El ejercicio produce efectos beneficiosos en la salud general de los individuos, y es indiscutible el papel que desempeña en el tratamiento y la prevención de la resistencia a la insulina y la diabetes tipo 2. Una sesión aguda de ejercicio o contracción muscular aumenta la captación de glucosa en el músculo esquelético a través de vías independientes de la insulina, y ello conduce a mejorías en la homeostasis corporal total de la glucosa. La actividad física regular induce cambios adaptativos en el músculo esquelético a través de modificaciones de la expresión de genes metabólicos. Estos cambios consisten en aumentos de las mitocondrias y modificaciones de la distribución de los tipos de fibras musculares. Un objetivo importante de la investigación sobre el ejercicio es el estudio de las señales moleculares que son inducidas por la actividad muscular y regulan los procesos metabólicos y transcripcionales clave en el músculo esquelético. En esta revisión, presentamos una breve panorámica general de la investigación sobre el ejercicio en el campo metabólico, describiendo diversas señales moleculares que subyacen en esos procesos. En este campo dinámico de investigación, se está realizando una búsqueda de otras proteínas de señalización estimuladas por el ejercicio. Los estudios que se realizan para aclarar en mayor medida las vías influidas por el ejercicio que intervienen en el transporte de glucosa, el tipo de fibra muscular y la biogénesis mitocondrial, permitirán comprender mejor cómo se producen los efectos favorables del ejercicio, mejorar nuestro conocimiento sobre los mecanismos patológicos de las enfermedades metabólicas como la diabetes tipo 2 e identificar nuevas dianas farmacológicas para el tratamiento (AU)

Exercise has beneficial effects on overall health, and its role in the treatment and prevention of insulin resistance and type 2 diabetes is undisputed. An acute bout of exercise or muscle contraction increases glucose uptake into skeletal muscle through insulin independent pathways, which leads to improvements in whole body glucose homeostasis. Regular physical activity induces adaptative changes in skeletal muscle through modification of metabolic gene expression. Such changes include increases in mitochondria and alteration of muscle fiber type distribution. An important goal of exercise research is to study molecular signals that are induced by muscle activity and that regulate key metabolic and transcriptional events in skeletal muscle. In this review, we give a brief overview of exercise research in the metabolic field, describing a number of molecular signals underlying these events. In this dynamic field of research the search for additional exercise-stimulated signalling proteins is ongoing. Studies to further elucidate exercise-mediated pathways involved in glucose transport, muscle fibre type and mitochondrial biogenesis will help to further understand the beneficial effects of exercise, to improve our knowledge about the pathological mechanisms of metabolic diseases such as type 2 diabetes, and to find new pharmacological targets for treatment (AU)

Programa de uso compasivo con adefovir dipivoxil en España: valoración de su eficacia y estudio de las resistencias / Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis

Fundamento y objetivo: El tratamiento prolongado con lamivudina de los pacientes con hepatitis B crónica se asocia a la emergencia de resistencias. Los pacientes con resistencia a la lamivudina presentan una pérdida de la respuesta tanto bioquímica como virológica y una mayor progresión de la enfermedad hepática. El adefovir dipivoxil, un análogo de los nucleótidos, es eficaz en el tratamiento de los pacientes con resistencia a la lamivudina. El objetivo de este estudio ha sido evaluar la eficacia, la seguridad y las resistencias del adefovir dipivoxil en pacientes con hepatitis B crónica refractarios al tratamiento con lamivudina. Pacientes y método: Se ha incluido a 120 pacientes afectados de hepatitis B crónica y refractarios al tratamiento con lamivudina que recibieron tratamiento con adefovir dipivoxil. En 74 de ellos se realizó seguimiento durante 2 años. En todos los casos se determinó el ADN del virus de la hepatitis B por reacción en cadena de la polimerasa, y en los casos sin respuesta al tratamiento se estudió la presencia de resistencias a adefovir dipivoxil y lamivudina. Resultados: A los 2 años de tratamiento se observó respuesta virológica en el 54,1% de los pacientes, respuesta bioquímica en el 62,2% y eliminación del antígeno e de la hepatitis B en el 21%. Se detectaron resistencias a adefovir dipivoxil en el 20% de los casos, y las mutaciones detectadas con mayor frecuencia fueron A181V, A181T y N236T. La seguridad del fármaco fue excelente, pues se detectó sólo un efecto adverso relacionado con el tratamiento. Conclusiones: El tratamiento durante 2 años con adefovir dipivoxil en monoterapia en pacientes previamente refractarios a lamivudina se asocia a una alta tasa de respuesta bioquímica y virológica, con una seguridad excelente. La tasa de resistencias al adefovir dipivoxil a los 2 años fue del 20%

Background and objective: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. Patients and method: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. Results: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. Conclusions: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%

Nuevas técnicas en el estudio del asma / New techniques in the study of asthma

El asma es consecuencia de la inflamación crónica de la vía aérea que se manifiesta funcionalmente como obstrucción variable al flujo aéreo e hiperreactividad bronquial. Con relativa frecuencia no disponemos de índices objetivos que nos permitan diagnosticar y controlar la enfermedad. Este artículo revisa técnicas adicionales de evaluación del funcionalismo pulmonar (provocación bronquial con adenosín-monofosfato, cuantificación de la resistencia al flujo aéreo por oscilometría de impulsos o pletismografía corporal) y de la respuesta inmunoinflamatoria bronquial (inducción de esputo, condensación de aire exhalado, monitorización de óxido nítrico en aire exhalado) y nuestra experiencia con su utilización. (AU)