0000000000341553
AUTHOR
Miguel Cerdá
Rolipram inhibits leukocyte-endothelial cell interactionsin vivothrough P- and E-selectin downregulation
1. Rolipram, a selective phosphodiesterase (PDE) type 4 inhibitor, was used to characterize leukocyte recruitment mechanisms in models of acute and subacute inflammation. Intravital microscopy within the rat mesenteric microcirculation was employed. 2. Mesentery superfusion with PAF (0.1 microM) induced a significant increase in leukocyte rolling flux, adhesion and emigration at 60 min. Rolipram pretreatment, markedly inhibited these parameters by 100, 95 and 95% respectively. 3. Similar effects were observed when the mesentery was superfused with LPS (1 microg ml(-1)) for the same time period and these leukocyte parameters were nearly abrogated by rolipram pretreatment. 4. LPS exposure of …
Inhibition of Xanthine Oxidase by Allopurinol Prevents Skeletal Muscle Atrophy: Role of p38 MAPKinase and E3 Ubiquitin Ligases
International audience; Abstract Top Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS) are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO). The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in ratsand its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinaseand the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, …
Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats
Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor a production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment wit…
Allopurinol partially prevents disuse muscle atrophy in mice and humans
AbstractDisuse muscle wasting will likely affect everyone in his or her lifetime in response to pathologies such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. We previously found that allopurinol, a drug widely used to treat gout, protects muscle damage after exhaustive exercise and results in functional gains in old individuals. Thus, we decided to test its effect in the prevention of soleus muscle atrophy after two weeks of hindlimb unloading in mice, and lower leg immobilization following ankle sprain in humans (EudraCT: 2011-003541-17). Our results show that allopurinol partially protects against muscle atrophy in both mice and humans. The pro…
Effect of simultaneous inhibition of TNF-α production and xanthine oxidase in experimental acute pancreatitis: The role of mitogen activated protein kinases
Javier Pereda et al.
Características de los electrogramas auriculares registrados en las líneas de bloqueo producidas con radiofrecuencia en un modelo experimental
Objetivos Analizar y cuantificar las modificaciones de los electrogramas auriculares tras la realizacion de lesiones lineales en la pared auricular utilizando procedimientos de ablacion con radiofrecuencia. Metodos En 12 preparaciones de corazon aislado de conejo segun la tecnica de Langendorff se ha utilizado un electrodo multiple epicardico (221 electrodos unipolares) para analizar la activacion auricular antes y despues de la realizacion de una lesion lineal en la pared auricular izquierda mediante aplicaciones sucesivas de radiofrecuencia. Tras comprobar la existencia de bloqueo de la conduccion en la zona lesionada mediante cartografia epicardica y analisis de los vectores de propagaci…
Oxidative Stress and Ubiquitin Ligases: their involvement in skeletal muscle atrophy
Introduction Muscle atrophy plays a relevant role in the many very prevalent diseases. Generation of reactive oxygen species (mainly by the xanthine oxidase) and inflammation are two of the main triggers of muscle atrophy. Aim The major aim of our study was to determine the mechanism by which reactive oxygen species activate E3 ubiquitin ligases (MuRF-1 and MAFbx) cause muscle atrophy. Possible prevention by allopurinol, a well-known xanthine oxidase inhibitor widely used in clinical practice; and by indomethacin, a non-steroidal antiinflamatory drug was also studied. Materials and methods Male C57BL/6J mice (3 months old) conditioned by 14 days of hindlimb unloading with or without each tr…
Ductal Carcinoma In Situ of the Breast: A Comparative Analysis of Histology, Nuclear Area, Ploidy, and Neovascularization Provides Differentiation Between Low- and High-Grade Tumors
Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that has been subdivided into three types: well differentiated (grade I), moderately differentiated (grade II), and poorly differentiated (grade III). Forty-five cases of DCIS were analyzed for image analysis: nuclear area, DNA ploidy, and vascularization in order to establish a more precise correlation between the histologic grade and these morphometric parameters. Our results confirm that the mean nuclear area, DNA ploidy, and microvessel density (MVD) progressively increased from DCIS grade I to DCIS grade III. The analysis of the nuclear area in relationship to DCIS grading demonstrated a progressive increase of values …