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Certain patients suffering from chronic diseases such as AIDS or cancer experience a constant cellular secretion of tumor necrosis factor and other pro-inflammatory cytokines that results in a continuous release of nitric oxide ( NO) to the bloodstream. One immediate consequence of the deleterious action of NO is weight loss and the progressive destruction of muscular mass in a process known as cachexia. We have previously reported that caveolin-3, a specific marker of muscle cells, becomes down-regulated by the action of NO on muscular myotubes. We describe herein that the changes observed in caveolin-3 levels are due to the alteration of the DNA binding activity of the muscular transcription factor myogenin. In the presence of NO, the binding of transcription factors from cell nuclear extracts of muscular tissues to the E boxes present in the caveolin-3 promoter become substantially reduced.When we purified recombinant myogenin and treated it with NO donors, we could detect its S-nitrosylation by three independent methods, suggesting that very likely one of the cysteine residues of the molecule is being modified. Given the role of myogenin as a regulatory protein that determines the level of multiple muscle genes expressed during late myogenesis, our results might represent a novel mode of regulation of muscle development under conditions of nitric oxide-mediated toxicity., Depto. de Bioquímica y Biología Molecular, Fac. de Farmacia, TRUE, pub

Septicemia is an emerging pathological condition involving, among other effects, refractory hypotension and heart dysfunction. Here we have investigated the contribution of resident nonmyocytic cells to heart alterations after lipopolysaccharide administration. These cells contributed to the rapid infiltration of additional inflammatory cells that enhance the onset of heart disease through the release of inflammatory mediators. Early activation of resident monocytic cells played a relevant role on the infiltration process, mainly of major histocompatibility complex class IIand CD11b-positive cells. This infiltration was significantly impaired in animals lacking the nitric-oxide synthase-2 (NOS-2) gene or after pharmacological inhibition of NOS-2 or cylooxygenase-2, suggesting a significant contribution of nitric oxide and prostanoids to the infiltration process. Under these conditions, the expression of NOS-2 and cylooxygenase-2 in the whole organ was attenuated because cardiomyocytes failed to express these enzymes. However, cardiomyocytes expressed and activated matrix metalloproteinase-9 through mechanisms regulated, at least in part, by nitric oxide and prostaglandins in an additive way. These results directly link the inflammatory response in the heart and extracellular matrix remodeling by the matrix metalloproteinases released by the cardiomyocytes, suggesting that activation and recruitment of inflammatory cells to the heart is a major early event in cardiac dysfunction promoted by septicemia. Copyright © American Society for Investigative Pathology.

Con el fin de contribuir al conocimiento de la sumplementación dietética en la evolución del estado nutritivo de pacientes con anorexia nerviosa en proceso de tratamiento, se evaluaron 3 grupos de adolescentes de sexo femenino diagnosticadas de AN desde la fase de ingreso hospitalario al alta. Se estudiaron 3 grupos de pacientes a los que se administró: a un grupo la dieta convencional del hospital, a otro 200 ml de suplemento dietético además de la dieta, y al tercero 400 ml del mismo sumplemento dietético junto con la dieta. Al ingreso y al alta hospitalaria se determinó: la ingesta de energía y nutrientes, parámetros antropométricos, bioquímicos, hematológicos e inmunológicos. Los resultados se compararon con los de un grupo control de 25 jóvenes sanas con las mismas características de edad, sexo y status socioeconómico

Several cell types express inducible nitric oxide synthase (NOS2) in response to exogenous insults such as bacterial lipopolysaccharide (LPS) or proinflammatory cytokines. For instance, muscular cells treated with LPS and interferon gamma (IFN-gamma) respond by increasing the mRNA and protein levels of NOS2, and synthesize large amounts of nitric oxide. We show here that transcriptional induction of NOS2 in muscular cells proceeds with a concomitant decrease in the levels of caveolin-1, -2 and -3. Addition of *NO-releasing compounds to C2C12 muscle cells reveals that this downregulation of the caveolin (cav) levels is due to the presence of *NO itself in the case of caveolin-3 and to the action of the LPS/IFN-gamma in the case of cav-1 and cav-2. Likewise, muscle cells obtained from NOS2(-/-) knockout mice challenged with LPS/IFN-gamma could downregulate their levels of cav-1 but not of cav-3, unlike wild-type animals, in which both cav-1 and cav-3 levels diminished in the presence of the proinflammatory insult. Laser confocal immunofluorescence analysis proves that *NO exerts autocrine and paracrine actions, hence diminishing the cav-3 levels. When the induced NOS2 was purified using an affinity resin or immunoprecipitated from muscular tissues, it appears strongly bound not only to calmodulin but also to cav-1, and marginally to cav-2 and cav-3. When the cav levels where reduced using antisense oligonucleotides, an increase in the NOS2-derived.NO levels could be measured, demonstrating the inhibitory role of the three cav isoforms. Our results show that cells expressing NOS2 diminish their cav levels when the synthesis of *NO is required.

Con el fin de contribuir al conocimiento de la sumplementación dietética en la evolución del estado nutritivo de pacientes con anorexia nerviosa en proceso de tratamiento, se evaluaron 3 grupos de adolescentes de sexo femenino diagnosticadas de AN desde la fase de ingreso hospitalario al alta. Se estudiaron 3 grupos de pacientes a los que se administró: a un grupo la dieta convencional del hospital, a otro 200 ml de suplemento dietético además de la dieta, y al tercero 400 ml del mismo sumplemento dietético junto con la dieta. Al ingreso y al alta hospitalaria se determinó: la ingesta de energía y nutrientes, parámetros antropométricos, bioquímicos, hematológicos e inmunológicos. Los resultados se compararon con los de un grupo control de 25 jóvenes sanas con las mismas características de edad, sexo y status socioeconómico

En este trabajo se utilizan linfocitos b humanos inmortalizados que han sido previamente mutados y que se caracterizan en este trabajo. Están afectados en el expresion en la superficie celular de hla-dp y en el procesamiento post-traduccional. Los datos obtenidos han puesto de manifiesto que existe una regulación diferencial de hla-dr, -dp y -dq, y que la complejidad del procesamiento y de la migración intracelular de estos antígenos es superior a lo descrito anteriormente