57,830 research outputs found
Vendrell - 25 cts. : L'Ajuntament d'El Vendrell pagarà al portador vint-i-cinc cèntims, maig del 1937
No full textSense cap emblema ni dibuix, emmarcat per una sanefa vertical a dreta i esquerra de l'anvers i al revers sols hi figura el valor de canvi enquadrat per unes orles. Color marró sobre fons vers a l'anvers, verd al revers ; emès el 1937; tiratge de 20.000 exemplars ; núm. 1678 ; Núm. del catàleg Turró: 3127 ; Índex de raresa: Corren
Emili Vendrell
No full textPla detall de la placa de l'Associació del
carrer en homenatge a la casa on el dia
13 de gener del 1893 va nèixer Emili
Vendrell Ibars. Mesura 0,40 x 0,65
metres i és de granit negre
A Emili Vendrell
No full textEl tamany total es de 1,62 x 10,80 x 1,95 metres, de pedra amb relleu i inscripcions de bronze.Solanic Balius Rafael(escultor); Clotet, Rosa Maria; Galí, Beth (arquitectes)Pla en detall de la imatge femenina en relleu filant del monument a Emili Vendrell. Aquesta figura representa el personatge de la balanguer
A Emili Vendrell
No full textEl tamany total es de 1,62 x 10,80 x 1,95 metres, de pedra amb relleu i inscripcions de bronze.Solanic Balius Rafael(escultor); Clotet, Rosa Maria; Galí, Beth (arquitectes)Pla general de la plaça amb l'obra. Relleu
al·legòric d'Emili Vendrell: una imatge
femenina filant, que representa el personatge
de "La balanguera".Solanic va fer en bronze i que, d'acord amb els cànons del classicisme, és una silueta hieràtic
Traces and shards of self-injury: Strange accounting with “Author X”
No full textIn this strange account autoethnography, three or four authors explore their lived experiences with self-injury. Strange accounting is both a post-modern style of text, and a method for keeping identities concealed when risks and secrets are in play. Author X, a post-modern place-keeper for an anonymous author who may or may not have contributed to this manuscript, introduces a new dimension and layer of concealment. With Author X in-play and under erasure, the reader will never be sure if there were three or four authors on this manuscript. Through strange accounting, a post-structuralist/postmodernist frame will be applied to understanding the self-injury experience. We frame self-injury as a social practice and, for some, an everyday norm, while remaining acutely aware of the stigma surrounding the topic of self-injury. Each of us, coupled with Author X, provide the others cover to trace stories of self-injury through the literature, our flesh, and our lives
Risk of Upper Gastrointestinal Bleeding and the Degree of Serotonin Reuptake Inhibition by antidepressant. A case control study
No full textBackground and objective: Selective serotonin reuptake inhibitor (SSRI) antidepressants can inhibit uptake of serotonin by platelets, and their use may predispose patients to bleeding. Case reports and observational studies from databases have suggested an association between the use of SSRIs and gastrointestinal bleeding. Their risk appears to be increased if they are concurrently used with aspirin (acetylsalicylic acid) or with other NSAIDs. With the aim of establishing the risk of major upper gastrointestinal bleeding associated with various groups of drugs, we performed a multicentre case-control study. We present the results related to the use of antidepressants by the degree of serotonin reuptake inhibition they
induce, the selectivity at monoamine transporters and the dose.
Methods: A population-based multicentre case-control study in 18 hospitals in
Spain and in Italy, including 2813 incident cases of upper gastrointestinal bleeding and 7193 matched controls. Regression analyses are based on 2783 cases and 7058 controls because of missing variable data. Odds ratios (ORs) of upper gastrointestinal bleeding for antidepressant drugs grouped by affinity for the serotonin transporter, selectivity and dose, with djustment for potential confounders were estimated.
Results: Overall, 84 (3.0%) cases and 160 (2.2%) controls had used a highaffinity serotonin reuptake inhibitor (SRI) antidepressant. Their use in the 7 days prior tothe index day was not associated with a substantially increased risk of upper gastrointestinal bleeding (OR = 1.24; 95% CI 0.88, 1.76). Forty-one (1.5%) cases and 26 (0.4%) controls had concurrently used a high-affinity SRI antidepressant and an NSAID. The OR of upper gastrointestinal bleeding among these concurrent users (8.32; 95% CI 4.69, 14.76) did not differ from that in users of NSAIDs only (7.82; 95% CI 6.79, 9.00). No significant association was found between the use of SSRIs and the risk of upper gastrointestinal bleeding, neither with the degree of affinity for the serotonin transporter, by the selectivity of each individual agent (101 cases [3.6%] vs 192 controls [2.7%]; OR = 1.23; 95% CI 0.90, 1.68), nor by dose.
Conclusions: The risk of upper gastrointestinal bleeding is not increased by the use of SRIs. An interaction with coadministered NSAIDs was not observed. If there is a risk associated to these drugs, it seems to be low and not an important cause of hospital admission due to upper gastrointestinal bleeding. However, additional studies may be warranted in subgroup populations at potentially increased risk of bleeding, such as older adults and men
Upper Gastrointestinal Bleeding Associated With Antiplatelet Drugs
No full textBackground
The risk of major upper gastrointestinal bleeding associated with various antiplatelet drugs and the protection conferred by gastroprotective agents are not well defined.
Aim
To estimate the risk of upper gastrointestinal bleeding associated with the use of antiplatelet drugs and its prevention by gastroprotective agents.
Methods
In a case-control study, we compared all cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients over 18 years of age (2813 cases), with 7193 matched controls. Odds ratios of upper gastrointestinal bleeding for individual antiplatelet drugs with adjustment
for potential confounders were estimated.
Results
The individual risks of upper gastrointestinal bleeding were cardiovascular acetylsalicylic acid 4.0 (3.2–4.9), clopidogrel 2.3 (0.9–6.0), dipyridamole 0.9 (0.4–2.0), indobufen 3.8 (1.2–12.2), ticlopidine 3.1 (1.8–5.1) and triflusal 1.6 (0.9–2.7). Concomitant proton pump inhibitors decreased all risk estimates. For acetylsalicylic acid plus a proton pump inhibitor, the odds ratio was 1.1 (0.5–2.6). As a group, antiplatelet drugs accounted for 14.5% of all cases of upper gastrointestinal bleeding, i.e. 58 per million per year (334 per million per year among those older than 70 years).
Conclusions
The risk of upper gastrointestinal bleeding is substantially decreased by the concomitant use of proton pump inhibitors. The risk of acetylsalicylic acid plus a proton pump inhibitor seems lower than that of ticlopidine or clopidogrel
Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents
No full textAIM:
The relative gastrointestinal toxicity of NSAIDs in normal clinical practice is unknown. The aim of this study was to estimate the risk of upper gastrointestinal bleeding associated with NSAIDs and analgesics, with special emphasis on those agents that have been introduced in recent years.
DESIGN:
Multicentre case-control study.
PATIENTS:
All incident community cases of upper gastrointestinal bleeding from a gastric or duodenal lesion in patients aged >18 years of age (4309 cases). After secondary exclusions, 2813 cases and 7193 matched controls were included in the analysis.
SETTING:
Eighteen hospitals in Spain and Italy with a total study experience of 10,734,897 person-years.
MAIN OUTCOME MEASURE:
Odds ratios of upper gastrointestinal bleeding for each drug, with adjustment for potential confounders. For each individual drug the reference category was defined as those not exposed to the drug.
RESULTS:
The incidence of upper gastrointestinal bleeding was 401.4 per million inhabitants aged >18 years. Thirty-eight percent of cases were attributable to NSAIDs. Individual risks for each NSAID were dose dependent. Ketorolac was associated with the highest risk estimate (24.7; 95% CI 8.0, 77.0). For newer NSAIDs, the risks were as follows: aceclofenac 1.4 (95% CI 0.6, 3.3), celecoxib 0.3 (95% CI 0.03, 4.1), dexketoprofen 4.9 (95% CI 1.7, 13.9), meloxicam 5.7 (95% CI 2.2, 15.0), nimesulide 3.2 (95% CI 1.9, 5.6) and rofecoxib 7.2 (95% CI 2.3, 23.0). The risk was significantly increased in patients with a history of peptic ulcer and/or upper gastrointestinal bleeding, and in those taking antiplatelet drugs.
CONCLUSIONS:
NSAID-induced upper gastrointestinal bleeding is a common cause of hospital admission. Apart from the patient's history of peptic ulcer, its risk depends on the particular drug and its dose, and on concomitant treatments. Our results do not confirm that greater selectivity for COX-2 confers less risk of upper gastrointestinal bleeding
Discovery and characterizatopn of small molecular weight metallocarboxypeptidase inhibitors
No full textDescripció del recurs: el 02 de novembre de 2010Las hidrolasas son enzimas que catalizan la ruptura del enlace amida o peptódico, y por lo tanto son denominadas también proteasas o peptidasas. Las proteasas constituyen cerca del 2 % del genoma humano, lo que representa unos 600 productos génicos. De acuerdo con el residuo catalóticamente activo, existen seis grandes grupos de peptidasas. En este trabajo nos centraremos en la familia M14 de peptidasas, también denominadas metalocarboxipeptidasas (CPs) debido a que su actividad catalótica reside en el ion zinc presente en el sitio activo de la enzima. En el genoma humano, se han identificado al menos 26 genes que codifican carboxipeptidasas. Las peptidasas de la familia M14 que actúan en el tracto gastrointestinal son las principales metaloproteasas responsables de la obtención de aminoácidos libres de la proteína de la dieta. En otros compartimientos corporales, las CPs pueden llevar a cabo tareas especializadas y altamente reguladas como ser la maduración de neuropéptidos, citokinas y hormonas peptódicas. En algunos casos, una actividad catalótica fuera de control puede conducir a enfermedades. Cada vez existe una mayor evidencia experimental que demuestra la actividad carboxipeptidasa en procesos como la pancreatitis aguda, la diabetes, la inflamación, la fibrinólisis y el cáncer. A pesar de ciertos avances en algunos aspectos, la actividad específica de las CPs es pobremente conocida. Además, las carboxipeptidasas son blancos terapéuticos interesantes para el desarrollo de fármacos, y por lo tanto se ha decidido emplear una aproximación multi-disciplinaria para la identificación y caracterización de nuevas moléculas de bajo peso molecular capaces de interferir la actividad carboxipeptidasa. Así, en este trabajo se han combinado modernas herramientas computacionales, screening in vitro, modelado molecular y cristalografía de rayos X con el fin de obtener nuevas entidades quφmicas como base para el desarrollo de fármacos. Con base en herramientas computacionales, aplicando el método de Optimal Docking Areaö, se han caracterizado sitios de unión proteína-proteína y proteína-ligando en la superficie de las peptidasas de la familia M14. A partir de aquí, se identificó una nueva clase de compuestos químicos capaces de explotar las diferencias existentes entre enzimas de la familia por unión a regiones hidrofóbicas. Otros inhibidores fueron identificados mediante un screening in silico de grandes colecciones de compuestos. Ensayos in vitro demostraron que los compuestos líderes inhibieron de manera potente a las carboxipeptidasas blanco con otras características interesantes como la posibilidad de coordinación del ion zinc catalítico por intermedio de un anillo oxadiazol. A través de una colaboración con el Departamento de Química Orgánica se obtuvieron y caracterizaron nuevos compuestos químicos con conectividades atómicas novedosas que, inesperadamente, demostraron ser potentes inhibidores de carboxipeptidasas. Una clase adicional de molécula de bajo peso molecular caracterizada corresponde a inhibidores que se unen covalentemente al enzima blanco. En este caso, se logró obtener la estructura tridimensional del complejo a resolución atómica mediante cristalografφa de rayos X, lo que ha permitido el dise±o basado en la estructura de una nueva generación de compuestos. Basados en otros datos de cristalografía de rayos X y análisis computacional, se ha revisado y ampliado el mecanismo de acción catalítica de las peptidasas de la familia M14 a partir de una nueva forma cristalina de CPB a alta resolución. En conjunto, nuestro trabajo ha permitido la obtención de nuevas moléculas líderes de bajo peso molecular que podrían servir como base para futuros desarrollos en el diseño de fármacos y agentes de diagnóstico o imaginería dirigidos a metalocarboxipeptidasas fisiológicamente activas.Hydrolases are enzymes catalyzing the breakdown of the amide or peptide bond, and are therefore called proteases or peptidases as well. In the human genome, proteases made up about 2% of the genome, or about 600 gene products. There are six major groups of peptidases according to the catalytic residue. In our work we focused on the M14 family of peptidases, also called metallocarboxypeptidases (CPs) because of their catalytic activity hinges on the zinc ion present in the active site of the enzyme. In the human genome there are identified at least 26 genes encoding for CPs. M14 peptidases in the gastrointestinal tract are the main metalloproteases responsible of the liberation of free aminoacids from the protein content of the diet. In other compartments of the body, CPs may perform specialized and tightly controlled tasks such as neuropeptide, cytokine and hormone maturation. In some instances an imbalance in their activity leads to disease states in man. Increasing evidence shows carboxypeptidase involvement in acute pancreatitis, diabetes, inflammation, fibrinolysis and cancer. Although some aspects have become clearer, much of their activity remain poorly understood. Besides, carboxypeptidases are interesting targets for drug development, and therefore we pursued a multidisciplinary approach to identify and characterize novel small molecular weight compounds able to interfere carboxypeptidase activity. In this work we combined modern computational tools, in vitro screening, molecular modelling and X-ray crystallography to obtain new chemical entities useful as scaffolds for drug design. Based on a bioinformatics tools, the Optimal Docking Area method, we identified protein-protein and protein-ligand binding sites over the surface of M14 peptidases. This knowledge was employed to find out a new class of small molecular weight inhibitors which exploit the differential binding provided by hydrophobic patches. A further class of inhibitors was identified from in silico screening of collections of compounds. In vitro analysis revealed that the leads were potent inhibitors against the target proteases with interesting features like an oxadiazole zinc-chelating moiety. Compounds obtained from the Organic Chemistry Department were also screened, and unexpectedly, afforded some good inhibitors with unprecedented atomic bonding. One further class involved inhibitors that attach covalently to the target enzyme. In this case the structure of the complex obtained at high resolution by X-ray crystallography allowed the structure-guided design of new generation of compounds. The catalytic mechanism of M14 peptidases was also revisited based on our crystallographic and computational analysis of a new CPB crystal form at high resolution. Overall, our study provided new lead small molecular weight inhibitors which can be the foundation for further developments in the design of drugs and bioimaging or diagnostic agents targeted to physiologically-relevant metallocarboxypeptidases
The X-ray structure of carboxypeptidase a inhibited by a thiirane mechanism-based ihibitor
No full textThe three-dimensional X-ray crystal structure of carboxypeptidase A, a zinc-dependent hydrolase, covalently modified by a mechanism-based thiirane inactivator, 2-benzyl-3,4-epithiobutanoic acid, has been solved to 1.38 Å resolution. The interaction of the thiirane moiety of the inhibitor with the active site zinc ion promotes its covalent modification of Glu-270 with the attendant opening of the thiirane ring. The crystal structure determination at high resolution allowed for the clear visualization of the covalent ester bond to the glutamate side chain. The newly generated thiol from the inhibitor binds to the catalytic zinc ion in a monodentate manner, inducing a change in the zinc ion geometry and coordination, while its benzyl group fits into the S1' specificity pocket of the enzyme. The inhibitor molecule is distorted at the position of the carbon atom that is involved in the ester bond linkage on one side and the zinc coordination on the other. This particular type of thiirane-based metalloprotease inhibitor is for the first time analyzed in complex to the target protease at high resolution and may be used as a general model for zinc-dependent proteases.Fil: Fernández, Daniel. Universitat Autònoma de Barcelona; EspañaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Vendrell, Josep. Universitat Autònoma de Barcelona; EspañaFil: Avilés, Francesc X.. Universitat Autònoma de Barcelona; EspañaFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido
- …
