Diagnosis and management of the antiphospholipid syndrome

The antiphospholipid syndrome is a systemic autoimmune disease defined by thrombotic or obstetrical events that occur in patients with persistent antiphospholipid antibodies. Thrombotic antiphospholipid syndrome is characterized by venous, arterial, or microvascular thrombosis. Patients with catastrophic antiphospholipid syndrome present with thrombosis involving multiple organs. Obstetrical antiphospholipid syndrome is characterized by fetal loss after the 10th week of gestation, recurrent early miscarriages, intrauterine growth restriction, or severe preeclampsia.1 The major nonthrombotic manifestations of antiphospholipid-antibody positivity include valvular heart disease, livedo, antiphospholipidantibody-related nephropathy, thrombocytopenia, hemolytic anemia, and cognitive dysfunction. The antiphospholipid syndrome is often associated with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE); however, it commonly occurs without other autoimmune manifestations (primary antiphospholipid syndrome)

A financial analysis of born-global firms: evidence from Spain

From the beginning of the 1970s to the present day, significant changes have taken place in the competitive and organizational behavior of small and medium-sized companies (SMEs). Recently, some of these factors have applied more intensively, and this has given rise to growth in the number of new companies that undertake overseas operations almost immediately (known as born globals). The phenomenon of early internationalization is relatively recent, so there are still many aspects that need to be studied. The objective of this study is to contribute to the scarce empirical literature existing in Spain on this topic, by providing evidence on the possible differences in character of the born-global firms compared with the rest of exporting companies. To this end, the focus of the study is on the analysis of variables such as the size and sector of activity of these companies, and their principal economic and financial magnitudes. A sample of 1,324 Spanish SMEs that were exporting in 2007 was surveyed; of this total approximately 12% identified themselves as having adopted early internationalization. The results obtained indicate that the born-global firms are, on average, smaller; they are classified mostly to the services sector; and they are much more leveraged than the rest of Spanish SMEs that export

Knock, knock, knocking on muscle doors. Visions of the transport of substrates across the plasma membrane in muscle

El múscul té un paper central en el metabolisme. Així, el múscul utilitza quantitats substancials de glucosa durant l'estat absortiu, i els canvis en la captació muscular de la glucosa provoquen alteracions en la utilització global de la glucosa per l'organisme sencer. El múscul constitueix també el principal reservori corporal d'aminoàcids i de proteïnes. A més, el metabolisme muscular és mantingut mitjantçant l'activitat de molts diferents transportadors localitzats a la membrana plasmàtica, com són els transportadors de glucosa, carnitina, creatina o aminoàcids; aquests transportadors capten o alliberen, a través de la membrana plasmàtica de la cèl·lula muscular, diferents substrats o metabòlits. L'objectiu d'aquesta revisió consisteix en la caracterització molecular de les principals proteïnes transportadores presents a la membrana plasmàtica de les cèl·lules musculars, així com l'anàlisi de les seves propietats reguladores.Muscle is a major player in metabolism. It uses large amounts of glucose in the absorptive state and changes in muscle insulin-stimulated glucose uptake alter whole-body glucose disposal. Lipid substrates such as fatty acids or ketone bodies are preferentially used by muscle in certain physiological conditions. Muscle is also the main reservoir of amino acids and protein. The activity of many different plasma membrane transporters such as glucose carriers, carnitine, creatine or amino acid transporters maintain muscle metabolism by taking up or releasing substrates or metabolites across the cell surface. The goal of this review is the molecular characterization of muscle membrane transporter proteins and the analysis of their regulatory roles

A nationwide study of chronic pain prevalence in the general Spanish population, identifying clinical subgroups through cluster analysis.

Objective. This study aims to assess the prevalence of chronic pain, its characteristics, and its impact on the general Spanish population. Also, to establish chronic pain patient subgroups according to the characteristics of pain and to identify variables specifically associated with each subgroup. Design. Telephone-based, cross-sectional nationwide study. Subjects. A sample of 1,957 individuals representative of the Spanish population. Methods. Data were collected through telephone interviews. A subject was considered to have chronic pain if they had suffered pain (at least 4 days a week) during the last 3 months. The subjects were divided into two subgroups through a cluster analysis, and a regression model was established to determine the variables most specifically associated with these subgroups. Results. The prevalence of chronic pain was 16.6% (95% confidence interval: 14.9–18.3) and among these subjects, more than 50% referred to limitations in their daily activities, 30% felt sad and/or anxious, and 47.2% indicated that their pain was affecting their family life. Two subgroups of subjects with pain were identified: 1) characterized by generalized pain in more than one location and of a long evolution (150 months); and 2) characterized by pain localized to only one site with a shorter duration (100 months). Individuals who felt anxious because of their pain and those who considered that their pain was affecting their family were more likely to belong to group 1. Conclusions. Pain affects an important proportion of the Spanish adult population and that it has a strong personal impact. Two pain groups were clearly distinguished by their clinical characteristics

Phosphatidylinositol 3-Kinase inhibitors block differentiation of skeletal muscle cells

Skeletal muscle differentiation involves myoblast alignment, elongation, and fusion into multinucleate myotubes, together with the induction of regulatory and structural muscle-specific genes. Here we show that two phosphatidylinositol 3-kinase inhibitors, LY294002 and wortmannin, blocked an essential step in the differentiation of two skeletal muscle cell models. Both inhibitors abolished the capacity of L6E9 myoblasts to form myotubes, without affecting myoblast proliferation, elongation, or alignment. Myogenic events like the induction of myogenin and of glucose carrier GLUT4 were also blocked and myoblasts could not exit the cell cycle, as measured by the lack of mRNA induction of p21 cyclin-dependent kinase inhibitor. Overexpresssion of MyoD in 10T1/2 cells was not sufficient to bypass the myogenic differentiation blockade by LY294002. Upon serum withdrawal, 10T1/2-MyoD cells formed myotubes and showed increased levels of myogenin and p21. In contrast, LY294002-treated cells exhibited none of these myogenic characteristics and maintained high levels of Id, a negative regulator of myogenesis. These data indicate that whereas phosphatidylinositol 3-kinase is not indispensable for cell proliferation or in the initial events of myoblast differentiation, i.e. elongation and alignment, it appears to be essential for terminal differentiation of muscle cells

Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degradation in 3T3-L1 adipocytes

Caveolae are a specialized type of lipid rafts that are stabilized by oligomers of caveolin protein. Caveolae are particularly enriched in adipocytes. Here we analyzed the effects of caveolin-1 knockdown and caveolae ablation on adipocyte function. To this end, we obtained several multiclonal mouse 3T3-L1 cell lines with a reduced expression of caveolin-1 (95% reduction) by a small interfering RNA approach using lentiviral vectors. Control cell lines were obtained by lentiviral infection with lentiviral vectors encoding appropriate scrambled RNAs. Caveolin-1 knockdown adipocytes showed a drastic reduction in the number of caveolae (95% decrease) and cholera toxin labeling was reorganized in dynamic plasma membrane microdomains. Caveolin-1 depletion caused a specific decrease in glucose transporter 4 (GLUT4) and insulin receptor protein levels. This reduction was not the result of a generalized defect in adipocyte differentiation or altered gene expression but was explained by faster degradation of these proteins. Caveolin-1 knockdown adipocytes showed reductions in insulin-stimulated glucose transport, insulin-triggered GLUT4 recruitment to the cell surface, and insulin receptor activation. In all, our data indicate that caveolin-1 loss of function reduces maximal insulin response through lowered stability and diminished expression of insulin receptors and GLUT4. We propose that caveolin-1/caveolae control insulin action in adipose cells. Copyright © 2009 by The Endocrine Society.E.G.-M. was a Formación de Profesorado Universitario fellow from Ministerio de Educacion y Ciencia (MEC), Spain; M.C. was a Ramón y Cajal researcher from the MEC. This study was supported by research grants from the MEC (BMC2003-07279; BFU2006-13466/BMC; GEN2003-20662-C07), the Generalitat de Catalunya (2005SGR00947), and the Instituto de Salud Carlos III (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas).Peer Reviewe

El mercado alternativo bursátil: una oportunidad para Andalucía

Este estudio hace referencia a la reciente creación en España del Mercado Alternativo Bursátil (MAB) para empresas en expansión, un segmento del mercado especialmente enfocado a PYMES. Con este trabajo se trata de dar respuestas a numerosos interrogantes relativos al mismo en tres fases sucesivas: En primer lugar: ¿qué son los mercados financieros bursátiles alternativos en general?; en segundo término: ¿cómo va a funcionar el nuestro, el mercado alternativo bursátil español?; y finalmente: ¿cómo son y qué resultados vienen obteniendo otros mercados alternativos europeos similares

Estadística Básica con R y R-Commander

Los objetivos docentes se centran en introducir a los alumnos en los conceptos básicos de la Estadística Descriptiva y la Inferencia y en la resolución, a través del software estadístico R, de problemas de análisis de datos y cálculo de probabilidades. En concreto nos centramos en análisis exploratorio de una y dos variables, distribuciones de probabilidades, inferencia en una y dos poblaciones y análisis de la varianza unifactorialUniversidad de Cádi

Functional characterization of the alanine-serine-cysteine exchanger of Carnobacterium sp AT7

Many key cell processes require prior cell uptake of amino acids from the environment, which is facilitated by cell membrane amino acid transporters such as those of the L-type amino acid transporter (LAT) subfamily. Alterations in LAT subfamily amino acid transport are associated with several human diseases, including cancer, aminoacidurias, and neurodegenerative conditions. Therefore, from the perspective of human health, there is considerable interest in obtaining structural information about these transporter proteins. We recently solved the crystal structure of the first LAT transporter, the bacterial alanine-serine-cysteine exchanger of Carnobacterium sp AT7 (BasC). Here, we provide a complete functional characterization of detergent-purified, liposome-reconstituted BasC transporter to allow the extension of the structural insights into mechanistic understanding. BasC is a sodium- and proton-independent small neutral amino acid exchanger whose substrate and inhibitor selectivity are almost identical to those previously described for the human LAT subfamily member Asc-1. Additionally, we show that, like its human counterparts, this transporter has apparent affinity asymmetry for the intra- and extracellular substrate binding sites a key feature in the physiological role played by these proteins. BasC is an excellent paradigm of human LAT transporters and will contribute to our understanding of the molecular mechanisms underlying substrate recognition and translocation at both sides of the plasma membrane

Insulin-induced redistribution of GLUT4 glucose carriers in the muscle fiber

Insulin rapidly stimulates glucose transport in muscle fiber. This process controls the utilization of glucose in skeletal muscle, and it is deficient in various insulin-resistant states, such as non-insulin-dependent diabetes mellitus. The effect of insulin on muscle glucose transport is mainly due to the recruitment of GLUT4 glucose carriers to the cell surface of the muscle fiber. There is increasing evidence that the recruitment of GLUT4 carriers triggered by insulin affects selective domains of sarcolemma and transverse tubules. In contrast, GLUT1 is located mainly in sarcolemma and is absent in transverse tubules, and insulin does not alter its cellular distribution in muscle fiber. The differential distribution of GLUT1 and GLUT4 in the cell surface raises new questions regarding the precise endocytic and exocytic pathways that are functional in the muscle fiber. The current view of insulin-induced GLUT4 translocation is based mainly on studies performed in adipocytes. These studies have proposed the existence of intracellular compartments of GLUT4 that respond to insulin in a highly homogeneous manner. However, studies performed in skeletal muscle have identified insulin-sensitive as well as insulin-insensitive intracellular GLUT4-containing membranes. These data open a new perspective on the dynamics of intracellular GLUT4 compartments in insulin-sensitive cells