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2. Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia

Author

Huguet JM, Cortés X, Boscá-Watts MM, Muñoz M, Maroto N, Iborra M, Hinojosa E, Capilla M, Asencio C, Amoros C, and Paredes JM

Subjects
health-related quality of life, iron deficiency, inflammatory bowel disease, ferric carboxymaltose
Abstract

Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (

Published
2022

3. Traumatismo materno grave y cirugía múltiple con resultado perinatal exitoso

Author

Jorge Hasbun H, Susana Benitez S, Rodrigo Cornejo R, Ramón Asencio C, José Luis Navarro A, and Stefan Danilla E

Subjects
Embarazo, trauma, desforramiento, infección, cuidado intensivo, Pregnancy, skinning, infection, intensive care, Gynecology and obstetrics, RG1-991
Abstract

El traumatismo mayor de la embarazada es frecuente, tiene riesgo de muerte y agrega a sus complicaciones propias, las generadas por el embarazo como prematurez, desprendimiento placentario y daño perinatal. Presentamos el caso de una embarazada de 27 semanas, con traumatismo grave por atropello, fracturas óseas y desforramiento extenso de extremidad inferior derecha, que fue sometida a tratamiento quirúrgico con reducción y corrección de luxofracturas, aseo e injertos cutáneos. Se complica con infección grave de foco cutáneo, persistente, permaneciendo 24 días en Unidad de Cuidad Intensivo (UCI) en tratamiento antibiótico, 10 drenajes quirúrgicos, nutrición enteral y manejo continuo del dolor, antes del parto. Inicia síndrome de respuesta inflamatoria sistêmica y se efectúa operación cesárea. El recién nacido prematuro pesó 1500 gramos y evolucionó favorablemente. En su puerperio permanece 60 días hospitalizada en UCI con 14 cirugías de reparación y mejoría completa. Se analiza las características singulares de morbilidad materna del caso, discutiendo los aspectos obstétricos, quirúrgicos y de cuidado intensivo, la evolución materna, el manejo de la infección y el rol de la cirugía en la prolongación del embarazo y su influencia en el resultado perinatal exitoso. Se concluye la importancia de la integración multidisciplinaria en la toma de decisiones médicas y quirúrgicas en el manejo del trauma materno grave.Maternal trauma is a leading cause of morbidity and mortality for both, fetus and mother. In addition, trauma can generate risks as premature delivery, abruptio placentae and fetal damage. A pregnant women, at 27 gestational weeks had a car accident with dislocation and fractures and extensive skinning of right leg. The first surgery for fracture-dislocations, cleaning and muscle skin flap were complicated with infection from cutaneous focus, serious and persistent. She remainded for 24 days in Intensive Care Unit (ICU) with antibiotic therapy; she had 10 procedures of surgical drainage with anesthesia, catheter enteral nutrition and continuous pain medication before delivery. Then, she presented systemic inflammatory syndrome maternal and a cesarean section was done; the newborn weighted 1500 grams and had a favorable evolution. After delivery the mother stayed 60 days in ICU, with 14 reparatives surgeries and complete recovery. In this special patient with severe maternal morbidity we discuss the etiology of the oligoamnios observed, the maternal evolution in ICU, the handling of infection, the significance of surgical treatment in prolonging pregnancy and its influence on a successful perinatal outcome. We emphasize on the importance of a multidisciplinary approach in making the medical and surgical decisions in severe maternal trauma.

Published
2011

4. beta-Catenin-TCF/LEF signaling promotes steady-state and emergency granulopoiesis via G-CSF receptor upregulation

Author

Danek P, Kardosova M, Janeckova L, Karkoulia E, Vanickova K, Fabisik M, Lozano-Asencio C, Benoukraf T, Tirado-Magallanes R, Zhou Q, Burocziova M, Rahmatova S, Pytlik R, Brdicka T, Tenen D, Korinek V, and Alberich-Jorda M

Abstract

The canonical Wnt signaling pathway is mediated by interaction of beta-catenin with the T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcription factors and subsequent transcription activation of Wnt-target genes. In the hematopoietic system, the function of the pathway has been mainly investigated by rather unspecific genetic manipulations of beta-catenin that yielded contradictory results. Here, we used a mouse expressing a truncated dominant negative form of the human TCF4 transcription factor (dnTCF4) that specifically abrogates beta-catenin-TCF/LEF interaction. Disruption of the beta-catenin-TCF/LEF interaction resulted in the accumulation of immature cells and reduced granulocytic differentiation. Mechanistically, dnTCF4 progenitors exhibited downregulation of the Csf3r gene, reduced granulocyte colony-stimulating factor (G-CSF) receptor levels, attenuation of downstream Stat3 phosphorylation after G-CSF treatment, and impaired G-CSF-mediated differentiation. Chromatin immunoprecipitation assays confirmed direct binding of TCF/LEF factors to the promoter and putative enhancer regions of CSF3R. Inhibition of beta-catenin signaling compromised activation of the emergency granulopoiesis program, which requires maintenance and expansion of myeloid progenitors. Consequently, dnTCF4 mice were more susceptible to Candida albicans infection and more sensitive to 5-fluorouracil-induced granulocytic regeneration. Importantly, genetic and chemical inhibition of beta-catenin-TCF/LEF signaling in human CD34+ cells reduced granulocytic differentiation, whereas its activation enhanced myelopoiesis. Altogether, our data indicate that the beta-catenin-TCF/LEF complex directly regulates G-CSF receptor levels, and consequently controls proper differentiation of myeloid progenitors into granulocytes in steady-state and emergency granulopoiesis. Our results uncover a role for the beta-catenin signaling pathway in fine tuning the granulocytic production, opening venues for clinical intervention that require enhanced or reduced production of neutrophils. © 2020 by The American Society of Hematology.

Published
2020

5. Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey

Author

Adamo, Marianna, Byrne, Robert A., Baumbach, Andreas, Haude, Michael, Windecker, Stephan, Valgimigli, Marco, Aaroe, J., Abdeltawab, A. A., Accardi, R., Addad, F., Agostoni, P., Alajab, A., Alcázar, E., Alhabil, B., Altug Cakmak, H., Amico, F., Amoroso, G., Anderson, R., Andò, G., Andreou, A. Y., Antoniadis, D., Aquilina, M., Aramberry, L., Auer, J., Auffret, V., Ausiello, A., Austin, D., Avram, A., Ayman, E., Babunashvili, V., Bagur, R., Bakotic, Z., Balducelli, M., Ballesteros, S. M., Baptista, S., Baranauskas, A., Barbeau, G., Bax, M., Benchimol, C., Berroth, R., Biasco, L., Bilal, A., Binias, K., Blanco Mata, R., Boccuzzi, G., Bolognese, L., Boskovic, S., Bourboulis, N., Briguori, C., Bunc, M., Buysschaert, I., Calabro’, P., Campo, G., Candiello, A., Caprotta, U. F., Cardenas, M., Carrilho-Ferreira, P., Carrizo, S., Caruso, M., Cassar, A., Cernigliaro, C., Chacko, G., Chamie, D., Clapp, B., Coceani, M., Colangelo, S., Colombo, A., Comeglio, M., Connaughton, M., Conway, D., Cortese, B., Cosgrave, J., Costa, F., Couvoussis, E., Crimi, G., Crook, R., Cruz-Alvarado, J. E., Curello, S., D’Ascenzo, F., D’Urbano, M., Dana, A., De Backer, O., De Carlo, M., De Cesare, N., De Iaco, G., De La Torre, H. J. M., De Oliveira Netoj, B., Devlin, G. P., Di Lorenzo, E., Díaz, A., Dina, C., Dorsel, T. H., Eberli, F. R., Echeverría, R., Eftychiou, C., Elguindy, A., Ercilla, J., Ernst, A., Esposito, G., Ettori, F., Eufracino, Null, Ezquerra Aguilera, W., Falcone, C., Falu, R. M., Feres, F., Ferlini, M., Fernández, G., Fernández-Rodríguez, D., Fileti, L., Fischetti, D., Florescu, N., Formigli, D., Fouladvand, F., Franco, N., Fresco, C., Frigoli, E., Furmaniuk, J., Gabaldo, K., Galli, M., Galli, S., Garbo, R., Garducci, S., Garg, S., Gavrielatos, G., Gensch, J., Giacchi, G., Giunio, L., Giustino, G., Goldberg, L., Goldsmit, R., Gommeaux, A., González Godínez, H., Gosselin, G., Govorov, A., Grimfjard, P., Gross, E., Grosz, C., Guagliumi, G., Hadad, W., Hadadi, L., Hansen, P. R., Harb, S., Hatrick, R., Hayrapetyan, H. G., Hernández-Enríquez, M., Ho Heo, J., Horvath, I. G., Huan Loh, P., Ibrahim, A. M., Ierna, S., Ilic, I., Imperadore, F., Ionescu-Silva, E., Jacksch, R., James, S., Janiak, B., Jensen, S. E., Jeroen, S., Jugessur, R. K., Kala, P., Kambis, M., Kanakakis, J., Karamasis, G., Karchevsky, D., Karpovskiy, A., Kayaert, P., Kedev, S., Kemala, E., Ketteler, T., Khan, S. Q., Kharlamov, A., Kiernan, T., Kiviniem, T., Koltowski, L., Koskinas, K. C., Kouloumpinis, A., Kraaijeveld, A. O., Krizanic, F., Krötz, B., Kuczmik, W., Kukreja, N., Kuksa, D., Yav, K., Kyriakos, D., Labrunie, A., Laine, M., Lapin, O., Larosa, C., Latib, A., Lattuca, B., Lauer, B., Lefèvre, T., Legrand, V., Lehto, P., Leiva-Pons, J. L., Leone, A. M., Lev, G., Lim, R., Limbruno, U., Linares Vicente, J. A., Lindsay, S., Linnartz, C., Liso, A., Lluberas, R., Locuratolo, N., Lokshyn, S., Lunde, K., Lupi, A., Magnavacchi, P., Maia, F., Mainar, V., Mancone, M., Manolios, M. G., Mansour, S., Mariano, E., Marques, K., Martins, H., Mckenzie, D., Meco, S., Meemook, K., Mehmed, K., Melikyan, A., Mellwig, K. P., Mendiz, O. A., Merkulov, E., Mesquita, H. G., Mezzapelle, G., Miloradovic, V., Mohamed, S., Mohammed, B., Mohammed, F., Mohammed, K., Mohanad, A., Morawiec, B., More, R., Moreno-Martínez, F. L., Mrevlje, B., Muhammad, F., Näveri, H., Nazzaro, M. S., Neary, P., Negus, B. H., Nelson Durval, F. G., Nick, H., Nilva, E., Oldroyd, K. G., Olivares Asencio, C., Omerovic, E., Ortiz, M. A., Ota, H., Otasevic, P., Otieno, H. A., Paizis, I., Papp, E., Pasquetto, G., Patsourakos, N. G., Peels, J., Pelliccia, F., Pennacchi, M., Penzo, C., Perez, P., Perkan, A., Petrou, E., Phipathananunth, W., Pierri, A., Pinheiro, L. F., Pipa, J. L., Piva, T., Polad, J., Porto, I., Poveda, J., Predescu, L., Prog, R., Puri, R., Raco, D. L., Ramazan, O., Ramazzotti, V., Rao, S. V., Raungaard, B., Reczuch, K., Rekik, S., Rhouati, A., Rigattieri, S., Rodríguez-Olivares, R., Roik, M., Romagnoli, E., Román, A. J., Routledge, H., Rubartelli, P., Rubboli, A., Ruiz-García, J., Russo, F., Ruzsa, Z., Ryding, A., Saad, Aly, Sabate, M., Sabouret, P., Sadowski, M., Saia, F., Sanchez Perez, I., Santoro, G. M., Sarenac, D., Saririan, M., Sarma, J., Schuetz, T., Sciahbasi, A., Sebastian, M., Sebik, R., Sesana, M., Hur, Seung-Ho, Sganzerla, P., Shalva, R., Sharma, S., Sheiban, I., Shein, K. K., Shiekh, I. A., Sinha, M., Slhessarenko, J., Smith, D., Smyth, D. W., Sönmez, K., Sood, N., Sourgounis, A., Srdanovic, I., Stables, R. H., Stefanini, G. G., Stewart, J., Stoyanov, N., Suliman, A. A., Suryadevara, R., Suwannasom, P., Tange Veien, K., Tauchert, S., Tebet, M., Testa, L., Thury, A., Tilsted, H. H., Tiroch, K., Torres, A., Tosi, P., Traboulsi, M., Trani, C., Tresoldi, S., Tsigkas, G., Tueller, D., Turri, M., Udovichenko, A. E., Uretsky, B., Van Der Harst, P., Van Houwelingen, K. G., Vandoni, P., Vandormael, M., Varbella, F., Venkitachalam, C. G., Vercellino, M., Vidal-Perez, R., Vigna, C., Vignali, L., Vogt, F., Voudris, V., Vranckx, P., Vrolix, M., Vydt, T., Webster, M., Wijns, W., Woody, W., Wykrzykowska, J., Yazdani, S., Yildiz, A., Yurlevich, D., Zauith, R., Zekanovic, D., Zhao, M., Zimarino, M., Zingarelli, A., Abdelsamad, A. Y., Abo Shaera, E. S., Afshar, M. S., Agatiello, C., Aguiar, P., Ahmad, A. M., Akin, I., Alameda, M., Alegría-Barrero, E., Alejos, R., Alkhashab, K., Alkutshan, R. S. A., Almorraweh, A., Altnji, I., Alvarez Iorio, C., Anchidin, O., Angel, J., Antonopoulos, A., Apshilava, G., Arana, C., Ashikaga, T., Assomull, R., Atef, S. Z., Azmus, A. D., Azzalini, L., Azzouz, A., Baglioni, P., Bampas, G., Basil, M. P., Baumbach, A., Besh, D., Bhushan Sharm, A., Bien Hsien, H., Bihui, L., Bing-Chen, L., Biryukov, S., Blatt, A., Bocchi, E., Boghdady, A., Bonarjee, V. V. S., Bosnjak, I., Bravo Baptista, S., Brinckman, S. L., Buchter, B., Burzotta, F., Cacucci, M., Cagliyan, C. E., Calabrò, P., Cernetti, C., Chávez Mizraym, R., Choo, W. S., Choudhury, R., Cicco, N., Cisneros Clavijo, P., Çitaku, H., Collet, J. P., Consuegra-Sánchez, L., Conte, M., Corral, J. M., Damonte, A., Dangoisse, V., Dastani, M., Della Rosa, F., Deora, S., Devadathan, S., Dharma, S., Di Giorgio, A., Diez, J. L., Dinesha, B., Duplančić, D., El Behwashi, M. F., Elghawaby, H., Elshahawy, O., Eskola, M. J., Etman, A., Eun Gyu, L., Fabiano, L., Facta, A., Fan, Y., Fang-Yang, H., Farag, E., Fathi, Y., Fazeli, N., Federico, P., Fereidoun, M. Z., Fernandez-Nofrerias, E., Flensted Lassen, J., Flessas, D., Fouad, H., Franco-Pelaez, J. A., Fu, Q., Furtado, R., Gadepalli, R., Gallino, R., Gasparetto, V., Gentiletti, A., Gholoobi, A., Ghosh, A. K., Gkizas, S., Golchha, S. K., Goncharov, A., Gössl, M., Götberg, M., Greco, F., Grundeken, M. J., Gupta, D., Gupta, S., Guray, U., Hahalis, G., Hakim Vista, J., Hamid, M. A., Hammoudeh, A., Hasan, A. R. I., Hatsumura, F. E., Heintzen, M. P., Helal, T., Hetherington, S., Hewarathna, U. I., Hioki, H., Hissein, F., Ho-Ping, Y., Homs, S., Huber, K., Ibarra, F. M., Ielasi, A., Ipek, E., Jambunathan, R., Jamshidi, P., Jarrad, I., Javier, W., Jensen, J., Jimenez-Quevedo, P., Kalpak, O., Kan, J., Kanaan, T., Kao, D. H. M., Karamfiloff, K., Karegren, A., Karjalainen, P. P., Kasabov, R., Katsimagklis, G. D., Kaul, U., Khan, A., Kiemeneij, E., Kiviniemi, T., Kleiban, A., Komiyama, N., Konteva, M., Koshy, G., Krepsky, A. M., Kuljit, S., Kulkarni, P., Kumar, V., Kuznetsov, I., Lai, G., Lateef, M. A., Lawand, S., Le Hong, T., Lettieri, C., Levy, G., Lindvall, P., Maitra, A., Makowski, M., Mamas, M. A., Mandal, S. C., Mangalanandan, P., Marin, R., Mashhadi, M., Matsukage, T., Meier, B., Milosavljevic, B., Miro, S. S., Mitov, A., Moeriel, M., Moguel, R., Mohanty, A., Montalescot, G., Mörsdorf, W., Moscato, F., Muniz, A., Muraglia, S., Myć, J., Nada, A., Nair, P., Namazi, M. H., Naraghipour, F., Nguyen, Q. N., Nicosia, A., Nikas, D., Ober, M., Ocaranza-Sánchez, R., Olivecrona, G., Pahlajani, D., Pandey, B. P., Parma, A., Parma, R., Patsilinakos, S. P., Pattam, J., Peddi, S., Perez, P. R., Peruga, J. Z., Pescoller, F., Petrov, I., Piatti, L., Pico-Aracil, F., Pina, J., Piroth, Z., Popa, V., Pourbehi, M. R., Pradhan, A. K., Prida, X. E., Purohit, B. V., Pyun, W. B., Quang Hung, D., Rada, I., Rafizadeh, O., Rahman, M. A., Rai, L., Ramsewak, A., Ravindran, R., Rodriguez De Leiras, O. S., Rodríguez Esteban, M., Roque Figueira, H., Saket, A., Sakhov, O., Saktheeswaran, M. K., Salachas, A., Sallam, A., Sampaolesi, A., Samy, A., Sanchis, J., Santaera, O., Santarelli, A., Santharaj, W. S., Sarango, B., Satheesh, S., Schmitz, T., Schühlen, H., Seewoosagur, R., Segev, A., Seisembekov, V., Semitko, S., Sengottuvelu, G., Sepulveda Varela, P., Sethi, A., Sharma, A., Sharma, R. K., Shi, Hy., Şimşek, M. A., Siqueira, B., Skalidis, E., Slawin, J., Sorokhtey, L., Spaulding, C., Srinivas, B., Srinivasan, M., Stakos, D., Stefanini, G., Stojkovic, S., Tacoy, G., Tawade, M., Tiecco, F., Tondi, S., Torresani, E. M., Tousek, P., Tran, T., Trantalis, G., Triantafyllou, K., Trivedi, R., Trivisonno, A., Tsui, K. L., Türkoğlu, C., Tzung-Dau, W., Ueno, H., Urban, U., Uretsky, B. F., Uscumlic, A., Venugopal, V., Verney, R., Vilar, J. V., Villacorta, V. G., Vishwanath, R., Vlachojannis, G. J., Vlachojannis, M., Vlad, V., Von Birgelen, C., Vukcevic, V., Wahab, A., Waksman, R., Wei-Wen, L., Weisz, G., Whittaker, A., Yadav, A., Yokoi, Y., Zacharoulis, A., Zahran, M., Zamani, J., Ziakas, A., Zimmermann, J. P., Adamo, M., Byrne, R. A., Baumbach, A., Haude, M., Windecker, S., Valgimigli, M., Aaroe, J., Abdeltawab, A. A., Accardi, R., Addad, F., Agostoni, P., Alajab, A., Alcazar, E., Alhabil, B., Altug Cakmak, H., Amico, F., Amoroso, G., Anderson, R., Ando, G., Andreou, A. Y., Antoniadis, D., Aquilina, M., Aramberry, L., Auer, J., Auffret, V., Ausiello, A., Austin, D., Avram, A., Ayman, E., Babunashvili, V., Bagur, R., Bakotic, Z., Balducelli, M., Ballesteros, S. M., Baptista, S., Baranauskas, A., Barbeau, G., Bax, M., Benchimol, C., Berroth, R., Biasco, L., Bilal, A., Binias, K., Blanco Mata, R., Boccuzzi, G., Bolognese, L., Boskovic, S., Bourboulis, N., Briguori, C., Bunc, M., Buysschaert, I., Calabro', P., Campo, G., Candiello, A., Caprotta, U. F., Cardenas, M., Carrilho-Ferreira, P., Carrizo, S., Caruso, M., Cassar, A., Cernigliaro, C., Chacko, G., Chamie, D., Clapp, B., Coceani, M., Colangelo, S., Colombo, A., Comeglio, M., Connaughton, M., Conway, D., Cortese, B., Cosgrave, J., Costa, F., Couvoussis, E., Crimi, G., Crook, R., Cruz-Alvarado, J. E., Curello, S., D'Ascenzo, F., D'Urbano, M., Dana, A., De Backer, O., De Carlo, M., De Cesare, N., De Iaco, G., De La Torre, H. J. M., De Oliveira Netoj, B., Devlin, G. P., Di Lorenzo, E., Diaz, A., Dina, C., Dorsel, T. H., Eberli, F. R., Echeverria, R., Eftychiou, C., Elguindy, A., Ercilla, J., Ernst, A., Esposito, G., Ettori, F., Eufracino, Ezquerra Aguilera, W., Falcone, C., Falu, R. M., Feres, F., Ferlini, M., Fernandez, G., Fernandez-Rodriguez, D., Fileti, L., Fischetti, D., Florescu, N., Formigli, D., Fouladvand, F., Franco, N., Fresco, C., Frigoli, E., Furmaniuk, J., Gabaldo, K., Galli, M., Galli, S., Garbo, R., Garducci, S., Garg, S., Gavrielatos, G., Gensch, J., Giacchi, G., Giunio, L., Giustino, G., Goldberg, L., Goldsmit, R., Gommeaux, A., Gosselin, G., Govorov, A., Gonzalez Godinez, H., Gross, E., Grosz, C., Guagliumi, G., Hadad, W., Hadadi, L., Hansen, P. R., Harb, S., Hatrick, R., Hayrapetyan, H. G., Hernandez-Enriquez, M., Ho Heo, J., Horvath, I. G., Huan Loh, P., Ibrahim, A. M., Ierna, S., Ilic, I., Imperadore, F., Ionescu-Silva, E., Jacksch, R., James, S., Janiak, B., Jensen, S. E., Jeroen, S., Jugessur, R. K., Kala, P., Kambis, M., Kanakakis, J., Karamasis, G., Karchevsky, D., Karpovskiy, A., Kayaert, P., Kedev, S., Kemala, E., Ketteler, T., Khan, S. Q., Kharlamov, A., Kiernan, T., Kiviniem, T., Koltowski, L., Koskinas, K. C., Kouloumpinis, A., Kraaijeveld, A. O., Krizanic, F., Krotz, B., Kuczmik, W., Kukreja, N., Kuksa, D., Yav, K., Kyriakos, D., Labrunie, A., Laine, M., Lapin, O., Larosa, C., Latib, A., Lattuca, B., Lauer, B., Lefevre, T., Legrand, V., Lehto, P., Leiva-Pons, J. L., Leone, A. M., Lev, G., Lim, R., Limbruno, U., Linares Vicente, J. A., Lindsay, S., Linnartz, C., Liso, A., Lluberas, R., Locuratolo, N., Lokshyn, S., Lunde, K., Lupi, A., Magnavacchi, P., Maia, F., Mainar, V., Mancone, M., Manolios, M. G., Mansour, S., Mariano, E., Marques, K., Martins, H., Mckenzie, D., Meco, S., Meemook, K., Mehmed, K., Melikyan, A., Mellwig, K. P., Mendiz, O. A., Merkulov, E., Mesquita, H. G., Mezzapelle, G., Miloradovic, V., Mohamed, S., Mohammed, B., Mohammed, F., Mohammed, K., Mohanad, A., Morawiec, B., More, R., Moreno-Martinez, F. L., Mrevlje, B., Muhammad, F., Naveri, H., Nazzaro, M. S., Neary, P., Negus, B. H., Nelson Durval, F. G., Nick, H., Nilva, E., Oldroyd, K. G., Olivares Asencio, C., Omerovic, E., Ortiz, M. A., Ota, H., Otasevic, P., Otieno, H. A., Paizis, I., Papp, E., Pasquetto, G., Patsourakos, N. G., Peels, J., Pelliccia, F., Pennacchi, M., Penzo, C., Perez, P., Perkan, A., Petrou, E., Phipathananunth, W., Pierri, A., Pinheiro, L. F., Pipa, J. L., Piva, T., Polad, J., Porto, I., Poveda, J., Predescu, L., Prog, R., Puri, R., Raco, D. L., Ramazan, O., Ramazzotti, V., Rao, S. V., Raungaard, B., Reczuch, K., Rekik, S., Rhouati, A., Rigattieri, S., Rodriguez-Olivares, R., Roik, M., Romagnoli, E., Roman, A. J., Routledge, H., Rubartelli, P., Rubboli, A., Ruiz-Garcia, J., Russo, F., Ruzsa, Z., Ryding, A., Saad, A., Sabate, M., Sabouret, P., Sadowski, M., Saia, F., Sanchez Perez, I., Santoro, G. M., Sarenac, D., Saririan, M., Sarma, J., Schuetz, T., Sciahbasi, A., Sebastian, M., Sebik, R., Sesana, M., Hur, S. -H., Sganzerla, P., Shalva, R., Sharma, S., Sheiban, I., Shein, K. K., Shiekh, I. A., Sinha, M., Slhessarenko, J., Smith, D., Smyth, D. W., Sonmez, K., Sood, N., Sourgounis, A., Srdanovic, I., Stables, R. H., Stefanini, G. G., Stewart, J., Stoyanov, N., Suliman, A. A., Suryadevara, R., Suwannasom, P., Tange Veien, K., Tauchert, S., Tebet, M., Testa, L., Thury, A., Tilsted, H. H., Tiroch, K., Torres, A., Tosi, P., Traboulsi, M., Trani, C., Tresoldi, S., Tsigkas, G., Tueller, D., Turri, M., Udovichenko, A. E., Uretsky, B., Van Der Harst, P., Van Houwelingen, K. G., Vandoni, P., Vandormael, M., Varbella, F., Venkitachalam, C. G., Vercellino, M., Vidal-Perez, R., Vigna, C., Vignali, L., Vogt, F., Voudris, V., Vranckx, P., Vrolix, M., Vydt, T., Webster, M., Wijns, W., Woody, W., Wykrzykowska, J., Yazdani, S., Yildiz, A., Yurlevich, D., Zauith, R., Zekanovic, D., Zhao, M., Zimarino, M., Zingarelli, A., Abdelsamad, A. Y., Abo Shaera, E. S., Afshar, M. S., Agatiello, C., Aguiar, P., Ahmad, A. M., Akin, I., Alameda, M., Alegria-Barrero, E., Alejos, R., Alkhashab, K., Alkutshan, R. S. A., Almorraweh, A., Altnji, I., Alvarez Iorio, C., Anchidin, O., Angel, J., Antonopoulos, A., Apshilava, G., Arana, C., Ashikaga, T., Assomull, R., Atef, S. Z., Azmus, A. D., Azzalini, L., Azzouz, A., Baglioni, P., Bampas, G., Basil, M. P., Besh, D., Bhushan Sharm, A., Bien Hsien, H., Bihui, L., Bing-Chen, L., Biryukov, S., Blatt, A., Bocchi, E., Boghdady, A., Bonarjee, V. V. S., Bosnjak, I., Bravo Baptista, S., Brinckman, S. L., Buchter, B., Burzotta, F., Cacucci, M., Cagliyan, C. E., Cernetti, C., Chavez Mizraym, R., Choo, W. S., Choudhury, R., Cicco, N., Cisneros Clavijo, P., Citaku, H., Collet, J. P., Consuegra-Sanchez, L., Conte, M., Corral, J. M., Damonte, A., Dangoisse, V., Dastani, M., Della Rosa, F., Deora, S., Devadathan, S., Dharma, S., Di Giorgio, A., Diez, J. L., Dinesha, B., Duplancic, D., El Behwashi, M. F., Elghawaby, H., Elshahawy, O., Eskola, M. J., Etman, A., Eun Gyu, L., Fabiano, L., Facta, A., Fan, Y., Fang-Yang, H., Farag, E., Fathi, Y., Fazeli, N., Federico, P., Fereidoun, M. Z., Fernandez-Nofrerias, E., Flensted Lassen, J., Flessas, D., Fouad, H., Franco-Pelaez, J. A., Fu, Q., Furtado, R., Gadepalli, R., Gallino, R., Gasparetto, V., Gentiletti, A., Gholoobi, A., Ghosh, A. K., Gkizas, S., Golchha, S. K., Goncharov, A., Gossl, M., Gotberg, M., Greco, F., Grundeken, M. J., Gupta, D., Gupta, S., Guray, U., Hahalis, G., Hakim Vista, J., Hamid, M. A., Hammoudeh, A., Hasan, A. R. I., Hatsumura, F. E., Heintzen, M. P., Helal, T., Hetherington, S., Hewarathna, U. I., Hioki, H., Hissein, F., Ho-Ping, Y., Homs, S., Huber, K., Ibarra, F. M., Ielasi, A., Ipek, E., Jambunathan, R., Jamshidi, P., Jarrad, I., Javier, W., Jensen, J., Jimenez-Quevedo, P., Kalpak, O., Kan, J., Kanaan, T., Kao, D. H. M., Karamfiloff, K., Karegren, A., Karjalainen, P. P., Kasabov, R., Katsimagklis, G. D., Kaul, U., Khan, A., Kiemeneij, E., Kiviniemi, T., Kleiban, A., Komiyama, N., Konteva, M., Koshy, G., Krepsky, A. M., Kuljit, S., Kulkarni, P., Kumar, V., Kuznetsov, I., Lai, G., Lateef, M. A., Lawand, S., Le Hong, T., Lettieri, C., Levy, G., Lindvall, P., Maitra, A., Makowski, M., Mamas, M. A., Mandal, S. C., Mangalanandan, P., Marin, R., Mashhadi, M., Matsukage, T., Meier, B., Milosavljevic, B., Miro, S. S., Mitov, A., Moeriel, M., Moguel, R., Mohanty, A., Montalescot, G., Morsdorf, W., Moscato, F., Muniz, A., Muraglia, S., Myc, J., Nada, A., Nair, P., Namazi, M. H., Naraghipour, F., Nguyen, Q. N., Nicosia, A., Nikas, D., Ober, M., Ocaranza-Sanchez, R., Olivecrona, G., Pahlajani, D., Pandey, B. P., Parma, A., Parma, R., Patsilinakos, S. P., Pattam, J., Peddi, S., Perez, P. R., Peruga, J. Z., Pescoller, F., Petrov, I., Piatti, L., Pico-Aracil, F., Pina, J., Piroth, Z., Popa, V., Pourbehi, M. R., Pradhan, A. K., Prida, X. E., Purohit, B. V., Pyun, W. B., Quang Hung, D., Rada, I., Rafizadeh, O., Rahman, M. A., Rai, L., Ramsewak, A., Ravindran, R., Rodriguez De Leiras, O. S., Rodriguez Esteban, M., Roque Figueira, H., Saket, A., Sakhov, O., Saktheeswaran, M. K., Salachas, A., Sallam, A., Sampaolesi, A., Samy, A., Sanchis, J., Santaera, O., Santarelli, A., Santharaj, W. S., Sarango, B., Satheesh, S., Schmitz, T., Schuhlen, H., Seewoosagur, R., Segev, A., Seisembekov, V., Semitko, S., Sengottuvelu, G., Sepulveda Varela, P., Sethi, A., Sharma, A., Sharma, R. K., Shi, Hy., Simsek, M. A., Siqueira, B., Skalidis, E., Slawin, J., Sorokhtey, L., Spaulding, C., Srinivas, B., Srinivasan, M., Stakos, D., Stojkovic, S., Tacoy, G., Tawade, M., Tiecco, F., Tondi, S., Torresani, E. M., Tousek, P., Tran, T., Trantalis, G., Triantafyllou, K., Trivedi, R., Trivisonno, A., Tsui, K. L., Turkoglu, C., Tzung-Dau, W., Ueno, H., Urban, U., Uretsky, B. F., Uscumlic, A., Venugopal, V., Verney, R., Vilar, J. V., Villacorta, V. G., Vishwanath, R., Vlachojannis, G. J., Vlachojannis, M., Vlad, V., Von Birgelen, C., Vukcevic, V., Wahab, A., Waksman, R., Wei-Wen, L., Weisz, G., Whittaker, A., Yadav, A., Yokoi, Y., Zacharoulis, A., Zahran, M., Zamani, J., Ziakas, A., Zimmermann, J. P., and Cardiology

Subjects
Hirudin, Percutaneous, Antithrombin, medicine.medical_treatment, Psychological intervention, 030204 cardiovascular system & hematology, medical, 0302 clinical medicine, Peptide Fragment, Surveys and Questionnaires, Surveys and Questionnaire, Medicine, Bivalirudin, 030212 general & internal medicine, Societies, Medical, Transradial, Anticoagulant, Hirudins, Middle Aged, Recombinant Protein, Recombinant Proteins, Femoral Artery, Radial Artery, Cardiology, acute coronary syndrome, bivalirudin, transradial, adult, antithrombins, cardiology, femoral artery, hirudins, humans, middle aged, peptide fragments, percutaneous coronary intervention, recombinant proteins, societies, medical, surveys and questionnaires, attitude of health personnel, radial artery, Acute coronary syndrome, Cardiology and Cardiovascular Medicine, Human, medicine.drug, Adult, medicine.medical_specialty, Attitude of Health Personnel, medicine.drug_class, MEDLINE, Antithrombins, 03 medical and health sciences, societies, Percutaneous Coronary Intervention, Internal medicine, Humans, Acute Coronary Syndrome, Peptide Fragments, Management of acute coronary syndrome, business.industry, Percutaneous coronary intervention, medicine.disease, business
Abstract

AIMS Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. METHODS AND RESULTS A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. CONCLUSIONS The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

Published
2016
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24. Severe encephalopathy associated to pyruvate dehydrogenase mutations and unbalanced coenzyme Q(10) content

Author

Asencio C, Rodríguez-Hernandez MA, Briones P, Montoya J, Cortés A, Emperador S, Gavilán A, Ruiz-Pesini E, Yubero-Siles D, Montero-Sanchez R, Pineda M, O'Callaghan-Gordo M, Alcázar-Fabra M, Salviati L, Artuch-Iriberri R, and Navas P

Abstract

Coenzyme Q(10) (CoQ(10)) deficiency is associated to a variety of clinical phenotypes including neuromuscular and nephrotic disorders. We report two unrelated boys presenting encephalopathy, ataxia, and lactic acidosis, who died with necrotic lesions in different areas of brain. Levels of CoQ(10) and complex II+III activity were increased in both skeletal muscle and fibroblasts, but it was a consequence of higher mitochondria mass measured as citrate synthase. In fibroblasts, oxygen consumption was also increased, whereas steady state ATP levels were decreased. Antioxidant enzymes such as NQO1 and MnSOD and mitochondrial marker VDAC were overexpressed. Mitochondria recycling markers Fis1 and mitofusin, and mtDNA regulatory Tfam were reduced. Exome sequencing showed mutations in PDHA1 in the first patient and in PDHB in the second. These genes encode subunits of pyruvate dehydrogenase complex (PDH) that could explain the compensatory increase of CoQ(10) and a defect of mitochondrial homeostasis. These two cases describe, for the first time, a mitochondrial disease caused by PDH defects associated with unbalanced of both CoQ(10) content and mitochondria homeostasis, which severely affects the brain. Both CoQ(10) and mitochondria homeostasis appears as new markers for PDH associated mitochondrial disorders.

Published
2016

28. Traumatismo materno grave y cirugía múltiple con resultado perinatal exitoso

Author

Rodrigo Cornejo R, Jorge Hasbun H, Susana Benítez S, Stefan Danilla E, José Luis Navarro A, and Ramón Asencio C

Subjects
desforramiento, trauma, Embarazo, Obstetrics and Gynecology, infección, cuidado intensivo
Abstract

RESUMEN El traumatismo mayor de la embarazada es frecuente, tiene riesgo de muerte y agrega a sus complicaciones propias, las generadas por el embarazo como prematurez, desprendimiento placentario y dano perinatal. Presentamos el caso de una embarazada de 27 semanas, con traumatismo grave por atropello, fracturas oseas y desforramiento extenso de extremidad inferior derecha, que fue sometida a tratamiento quirurgico con reduccion y correccion de luxofracturas, aseo e injertos cutaneos. Se complica con infeccion grave de foco cutaneo, persistente, permaneciendo 24 dias en Unidad de Cuidad Intensivo (UCI) en tratamiento antibiotico, 10 drenajes quirurgicos, nutricion enteral y manejo continuo del dolor, antes del parto. Inicia sindrome de respuesta inflamatoria sistemica y se efectua operacion cesarea. El recien nacido prematuro peso 1500 gramos y evoluciono favorablemente. En su puerperio permanece 60 dias hospitalizada en UCI con 14 cirugias de reparacion y mejoria completa. Se analiza las caracteristicas singulares de morbilidad materna del caso, discutiendo los aspectos obstetricos, quirurgicos y de cuidado intensivo, la evolucion materna, el manejo de la infeccion y el rol de la cirugia en la prolongacion del embarazo y su influencia en el resultado perinatal exitoso. Se concluye la importancia de la integracion multidisciplinaria en la toma de decisiones medicas y quirurgicas en el manejo del trauma materno grave.PALABRAS CLAVE

Published
2011

29. Traumatismo materno grave y cirugía múltiple con resultado perinatal exitoso

Author

Hasbun H, Jorge, Benitez S, Susana, Cornejo R, Rodrigo, Asencio C, Ramón, Navarro A, José Luis, and Danilla E, Stefan

Subjects
desforramiento, trauma, Embarazo, Pregnancy, infección, skinning, cuidado intensivo, infection, intensive care
Abstract

El traumatismo mayor de la embarazada es frecuente, tiene riesgo de muerte y agrega a sus complicaciones propias, las generadas por el embarazo como prematurez, desprendimiento placentario y daño perinatal. Presentamos el caso de una embarazada de 27 semanas, con traumatismo grave por atropello, fracturas óseas y desforramiento extenso de extremidad inferior derecha, que fue sometida a tratamiento quirúrgico con reducción y corrección de luxofracturas, aseo e injertos cutáneos. Se complica con infección grave de foco cutáneo, persistente, permaneciendo 24 días en Unidad de Cuidad Intensivo (UCI) en tratamiento antibiótico, 10 drenajes quirúrgicos, nutrición enteral y manejo continuo del dolor, antes del parto. Inicia síndrome de respuesta inflamatoria sistêmica y se efectúa operación cesárea. El recién nacido prematuro pesó 1500 gramos y evolucionó favorablemente. En su puerperio permanece 60 días hospitalizada en UCI con 14 cirugías de reparación y mejoría completa. Se analiza las características singulares de morbilidad materna del caso, discutiendo los aspectos obstétricos, quirúrgicos y de cuidado intensivo, la evolución materna, el manejo de la infección y el rol de la cirugía en la prolongación del embarazo y su influencia en el resultado perinatal exitoso. Se concluye la importancia de la integración multidisciplinaria en la toma de decisiones médicas y quirúrgicas en el manejo del trauma materno grave. Maternal trauma is a leading cause of morbidity and mortality for both, fetus and mother. In addition, trauma can generate risks as premature delivery, abruptio placentae and fetal damage. A pregnant women, at 27 gestational weeks had a car accident with dislocation and fractures and extensive skinning of right leg. The first surgery for fracture-dislocations, cleaning and muscle skin flap were complicated with infection from cutaneous focus, serious and persistent. She remainded for 24 days in Intensive Care Unit (ICU) with antibiotic therapy; she had 10 procedures of surgical drainage with anesthesia, catheter enteral nutrition and continuous pain medication before delivery. Then, she presented systemic inflammatory syndrome maternal and a cesarean section was done; the newborn weighted 1500 grams and had a favorable evolution. After delivery the mother stayed 60 days in ICU, with 14 reparatives surgeries and complete recovery. In this special patient with severe maternal morbidity we discuss the etiology of the oligoamnios observed, the maternal evolution in ICU, the handling of infection, the significance of surgical treatment in prolonging pregnancy and its influence on a successful perinatal outcome. We emphasize on the importance of a multidisciplinary approach in making the medical and surgical decisions in severe maternal trauma.

Published
2011

31. Association between entero-hepaticHelicobacterspecies and Crohn’s disease: a prospective cross-sectional study

Author

LAHARIE, D., primary, ASENCIO, C., additional, ASSELINEAU, J., additional, BULOIS, P., additional, BOURREILLE, A., additional, MOREAU, J., additional, BONJEAN, P., additional, LAMARQUE, D., additional, PARIENTE, A., additional, SOULÉ, J.-C., additional, CHARACHON, A., additional, COFFIN, B., additional, PEREZ, P., additional, MÉGRAUD, F., additional, and ZERBIB, F., additional

Published
2009
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33. P199 ENTERO-HEPATIC HELICOBACTER SPECIES AND POSTOPERATIVE RECURRENCE OF CROHN'S DISEASE: PRELIMINARY RESULTS OF A PROSPECTIVE CASE-CONTROL STUDY

Author

Laharie, D., primary, Asencio, C., additional, Bulois, P., additional, Bourreille, A., additional, Moreau, J., additional, Bonjean, P., additional, Lamarque, D., additional, Pariente, E.A., additional, Soule, J.C., additional, Charachon, A., additional, Megraud, F., additional, and Zerbib, F., additional

Published
2007
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35. P1898 HIV–related morbidity in the HAART era

Author

Escobar, M.A., primary, Garcia-Egido, A.A., additional, Romero, S.P., additional, Bernal, J.A., additional, Puerto, J.L., additional, Gonzalez-Outon, J., additional, Asencio, C., additional, and Gomez, F., additional

Published
2007
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36. A desk spectrofluorometer for in-vivo and in-situ biological material measurements.

Author

García, E. Moreno, de la Rosa Vázquez, J. M., Fabíla Bustos, D. A., Gutiérrez, N. Pérez, Asencio, C. Mujica, and Domíngez-Cherit, J.

Subjects
FLUORESCENCE, SPECTRUM analysis, TISSUES, BIFURCATION theory, ORGANIC compounds
Abstract

Copyright of Revista Mexicana de Ingeniería Biomédica is the property of Sociedad Mexicana de Ingenieria Biomedica, A.C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2009

40. Modulation of Helicobacter pylori NAD(P)H: flavin oxidoreductase activity by intracellular oxygen.

Author

Mendz, G.L., Asencio, C., and Mégraud, F.

Subjects
*HELICOBACTER pylori, *NAD (Coenzyme), *OXIDOREDUCTASES
Abstract

Background. There is agreement that both RdxA, a membrane-associated oxygen-independent NADPH-nitroreductase, and FrxA, a cytosolic NAD(P)H:flavin oxidoreductase, are involved in the resistance of Helicobacter pylori to metronidazole, but there are conflicting views regarding their roles in the susceptibility of the bacterium to the drug. Aim. To characterise the kinetic properties of H. pylori FrxA in matched strains with intact or mutated frxA genes, and the properties of the enzyme expressed in an E. coli strain which lacks frxA. Results. Cytosolic extracts of H. pylori strains expressing FrxA had lower K[sub m] for the reduction of nitrofurazone (redox potential -257 mV) than the corresponding matched strains with mutated frxA. Only strains expressing FrxA were able to reduce metronidazole (redox potential -415 mV). Cell extracts of E. coli transformed with a plasmid carrying frxA had lower K[sub m] for the reduction of nitrofurazone than the parent strain or a strain transformed with the same plasmid but without frxA. The K[sub m] for nitrofurazone reduction of strains expressing FrxA depended also on the incubation conditions. Extracts from E. coli cells grown under microaerophilic conditions had significantly lower Km than those grown aerobically. Only transformed E. coli strains expressing FrxA and grown under microaerophilic conditions were able to reduce metronizadole, and no reduction of this low redox compound was observed in these strains when they were grown aerobically. The characteristics of flavin adenine dinucleotide reduction by transformed and untransformed E. coli strains were similar to those determined for metronidazole. Conclusions: The results from this study demonstrate directly the involvement of FrxA in the reduction of nitro compounds with low redox potential in H. pylori and in E. coli strains transformed with frxA, and the modulation of FrxA properties in the latter by the intracellular redox status. [ABSTRACT FROM AUTHOR]

Published
2002

43. Ultrasound transmural healing correlates with higher adalimumab drug concentration in Crohn's disease only in the short-term.

Author

Lorente JR, Paredes JM, Llopis P, Ripollés T, Voces A, Algarra Á, Asencio C, Latorre P, Moreno N, López-Serrano A, and Moreno-Osset E

Subjects
Humans, Female, Male, Retrospective Studies, Cross-Sectional Studies, Adult, Middle Aged, Anti-Inflammatory Agents therapeutic use, Anti-Inflammatory Agents pharmacokinetics, Anti-Inflammatory Agents blood, Young Adult, Adalimumab therapeutic use, Adalimumab blood, Crohn Disease drug therapy, Crohn Disease diagnostic imaging, Crohn Disease blood, Ultrasonography
Abstract

Background: anti-TNF drugs have revolutionized the treatment of Crohn's disease (CD) and have set new therapeutic targets. A direct correlation between anti-TNF trough levels and endoscopic healing in inflammatory bowel disease (IBD) patients has been established, but the association between drug levels and transmural healing assessed by ultrasound is not yet clearly defined., Aims: to evaluate the correlation between the serum concentration of adalimumab (ADA) and sonographic transmural healing in CD patients at different times during follow-up., Methods: in this retrospective, cross-sectional study, all patients with CD who were undergoing treatment with ADA in our center were included. Intestinal ultrasound (IUS) was performed before the initiation of the drug and for response monitoring. ADA serum-trough levels were compared between patients with and without transmural healing at different periods of time., Results: ninety-two patients were included, and all patients showed signs of inflammatory activity in the baseline IUS. During IUS monitoring of the response to ADA, 34 (34.8 %) patients presented transmural healing. Among patients in the first year of treatment, those with sonographic healing showed higher median levels than patients without transmural healing (12.0 µg/ml vs 9.3 µg/ml, respectively; p = 0.007). There was no correlation between ADA levels and sonographic healing in patients undergoing treatment for over a year., Conclusions: higher ADA trough levels correlated with transmural healing with ultrasound during the first year of treatment. This correlation was not found after one year of treatment.

Published
2024
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44. Streptococcus pyogenes Cas9 ribonucleoprotein delivery for efficient, rapid and marker-free gene editing in Trypanosoma and Leishmania.

Author

Asencio C, Hervé P, Morand P, Oliveres Q, Morel CA, Prouzet-Mauleon V, Biran M, Monic S, Bonhivers M, Robinson DR, Ouellette M, Rivière L, Bringaud F, and Tetaud E

Subjects
Streptococcus pyogenes genetics, Streptococcus pyogenes metabolism, Leishmania genetics, Leishmania metabolism, CRISPR-Associated Protein 9 genetics, CRISPR-Associated Protein 9 metabolism, RNA, Guide, CRISPR-Cas Systems genetics, RNA, Guide, CRISPR-Cas Systems metabolism, Trypanosoma brucei brucei genetics, Trypanosoma brucei brucei metabolism, Trypanosoma genetics, Trypanosoma metabolism, Transfection, Gene Editing methods, CRISPR-Cas Systems, Ribonucleoproteins metabolism, Ribonucleoproteins genetics
Abstract

Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including Trypanosoma congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 (SpCas9) and an in vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete, and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense, and Leishmania promastigotes. The functionality of SpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics but requires only cloning and PCR screening of the clones. Importantly, this approach is adaptable to any wild-type parasite., (© 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Published
2024
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45. Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells.

Author

Pradenas C, Luque-Campos N, Oyarce K, Contreras-Lopez R, Bustamante-Barrientos FA, Bustos A, Galvez-Jiron F, Araya MJ, Asencio C, Lagos R, Herrera-Luna Y, Abba Moussa D, Hill CN, Lara-Barba E, Altamirano C, Ortloff A, Hidalgo-Fadic Y, Vega-Letter AM, García-Robles MLÁ, Djouad F, Luz-Crawford P, and Elizondo-Vega R

Subjects
Humans, Male, Animals, Mice, Mice, Inbred C57BL, Immunosuppressive Agents, Cell Differentiation, Lactic Acid, Mesenchymal Stem Cells
Abstract

Background: The metabolic reprogramming of mesenchymal stem/stromal cells (MSC) favoring glycolysis has recently emerged as a new approach to improve their immunotherapeutic abilities. This strategy is associated with greater lactate release, and interestingly, recent studies have proposed lactate as a functional suppressive molecule, changing the old paradigm of lactate as a waste product. Therefore, we evaluated the role of lactate as an alternative mediator of MSC immunosuppressive properties and its contribution to the enhanced immunoregulatory activity of glycolytic MSCs., Materials and Methods: Murine CD4 + T cells from C57BL/6 male mice were differentiated into proinflammatory Th1 or Th17 cells and cultured with either L-lactate, MSCs pretreated or not with the glycolytic inductor, oligomycin, and MSCs pretreated or not with a chemical inhibitor of lactate dehydrogenase A (LDHA), galloflavin or LDH siRNA to prevent lactate production. Additionally, we validated our results using human umbilical cord-derived MSCs (UC-MSCs) in a murine model of delayed type 1 hypersensitivity (DTH)., Results: Our results showed that 50 mM of exogenous L-lactate inhibited the proliferation rate and phenotype of CD4 + T cell-derived Th1 or Th17 by 40% and 60%, respectively. Moreover, the suppressive activity of both glycolytic and basal MSCs was impaired when LDH activity was reduced. Likewise, in the DTH inflammation model, lactate production was required for MSC anti-inflammatory activity. This lactate dependent-immunosuppressive mechanism was confirmed in UC-MSCs through the inhibition of LDH, which significantly decreased their capacity to control proliferation of activated CD4 + and CD8 + human T cells by 30%., Conclusion: These findings identify a new MSC immunosuppressive pathway that is independent of the classical suppressive mechanism and demonstrated that the enhanced suppressive and therapeutic abilities of glycolytic MSCs depend at least in part on lactate production., (© 2023. The Author(s).)

Published
2023
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46. Small noncoding RNA interactome capture reveals pervasive, carbon source-dependent tRNA engagement of yeast glycolytic enzymes.

Author

Asencio C, Schwarzl T, Sahadevan S, and Hentze MW

Subjects
Proteome genetics, RNA metabolism, RNA Polymerase III metabolism, Glycolysis genetics, RNA, Transfer genetics, RNA, Transfer metabolism, RNA-Binding Proteins genetics, RNA-Binding Proteins metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, RNA, Small Untranslated genetics, RNA, Small Untranslated metabolism
Abstract

Small noncoding RNAs fulfill key functions in cellular and organismal biology, typically working in concert with RNA-binding proteins (RBPs). While proteome-wide methodologies have enormously expanded the repertoire of known RBPs, these methods do not distinguish RBPs binding to small noncoding RNAs from the rest. To specifically identify this relevant subclass of RBPs, we developed small noncoding RNA interactome capture (snRIC 2C ) based on the differential RNA-binding capacity of silica matrices (2C). We define the S. cerevisiae proteome of nearly 300 proteins that specifically binds to RNAs smaller than 200 nt in length (snRBPs), identifying informative distinctions from the total RNA-binding proteome determined in parallel. Strikingly, the snRBPs include most glycolytic enzymes from yeast. With further methodological developments using silica matrices, 12 tRNAs were identified as specific binders of the glycolytic enzyme GAPDH. We show that tRNA engagement of GAPDH is carbon source-dependent and regulated by the RNA polymerase III repressor Maf1, suggesting a regulatory interaction between glycolysis and RNA polymerase III activity. We conclude that snRIC 2C and other 2C-derived methods greatly facilitate the study of RBPs, revealing previously unrecognized interactions., (© 2023 Asencio et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Published
2023
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47. Intra-Abdominal Hypertension: A Systemic Complication of Severe Acute Pancreatitis.

Author

Mancilla Asencio C and Berger Fleiszig Z

Subjects
Abdomen, Acute Disease, Humans, Prognosis, Intra-Abdominal Hypertension complications, Intra-Abdominal Hypertension therapy, Pancreatitis complications, Pancreatitis therapy
Abstract

Patients with severe acute pancreatitis (SAP) present complications and organ failure, which require treatment in critical care units. These extrapancreatic complications determine the clinical outcome of the disease. Intra-abdominal hypertension (IAH) deteriorates the prognosis of SAP. In this paper, relevant recent literature was reviewed, as well as the authors' own experiences, concerning the clinical importance of IAH and its treatment in SAP. The principal observations confirmed that IAH is a frequent consequence of SAP but is practically absent in mild disease. Common manifestations of AP such as pain, abdominal distension, and paralytic ileus contribute to increased abdominal pressure, as well as fluid loss in third space and aggressive fluid replacement therapy. A severe increase in IAP can evolve to abdominal compartment syndrome and new onset organ failure. Conservative measures are useful, but invasive interventions are necessary in several cases. Percutaneous drainage of major collections is preferred when possible, but open decompressive laparotomy is the final possibility in some cases in order to definitively reduce abdominal pressure. Intra-abdominal pressure should be measured in all SAP cases that worsen despite adequate treatment in critical care units. Conservative measures must be introduced to treat IAH, including negative fluid balance, digestive decompression by gastric-rectal tube, and prokinetics, including neostigmine. In the case of insufficient responses to these measures, minimally invasive interventions should be preferred.

Published
2022
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48. Glycerol, a possible new player in the biology of trypanosomes.

Author

Bringaud F, Plazolles N, Pineda E, Asencio C, Villafraz O, Millerioux Y, Rivière L, and Tetaud E

Subjects
Biology, Humans, Glycerol metabolism, Trypanosoma brucei brucei metabolism, Trypanosomiasis, African parasitology
Abstract

Competing Interests: The authors have declared that no competing interests exist

Published
2021
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49. Circadian PERformance in breast cancer: a germline and somatic genetic study of PER3 VNTR polymorphisms and gene co-expression.

Author

Fores-Martos J, Cervera-Vidal R, Sierra-Roca J, Lozano-Asencio C, Fedele V, Cornelissen S, Edvarsen H, Tadeo-Cervera I, Eroles P, Lluch A, Tabares-Seisdedos R, Falcó A, Van't Veer LJ, Schmidt M, Quigley DA, Børresen-Dale AL, Kristensen VN, Balmain A, and Climent J

Abstract

Polymorphisms in the PER3 gene have been associated with several human disease phenotypes, including sleep disorders and cancer. In particular, the long allele of a variable number of tandem repeat (VNTR) polymorphism has been previously linked to an increased risk of breast cancer. Here we carried out a combined germline and somatic genetic analysis of the role of the PER3 VNRT polymorphism in breast cancer. The combined data from 8284 individuals showed a non-significant trend towards increased breast cancer risk in the 5-repeat allele homozygous carriers (OR = 1.17, 95% CI: 0.97-1.42). We observed allelic imbalance at the PER3 locus in matched blood and tumor DNA samples, showing a significant retention of the long variant (risk) allele in tumor samples, and a preferential loss of the short repetition allele (p = 0.0005). Gene co-expression analysis in healthy and tumoral breast tissue samples uncovered significant associations between PER3 expression levels with those from genes which belong to several cancer-associated pathways. Finally, relapse-free survival (RFS) analysis showed that low expression levels of PER3 were linked to a significant lower RSF in luminal A (p = 3 × 10 -12 ) but not in the rest of breast cancer subtypes., (© 2021. The Author(s).)

Published
2021
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50. Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.

Author

Allmann S, Wargnies M, Plazolles N, Cahoreau E, Biran M, Morand P, Pineda E, Kulyk H, Asencio C, Villafraz O, Rivière L, Tetaud E, Rotureau B, Mourier A, Portais JC, and Bringaud F

Subjects
Adenosine Triphosphate metabolism, Cell Line, Glycerol metabolism, Glycerol Kinase metabolism, Hexokinase metabolism, Microbodies enzymology, Trypanosoma brucei brucei metabolism
Abstract

Microorganisms must make the right choice for nutrient consumption to adapt to their changing environment. As a consequence, bacteria and yeasts have developed regulatory mechanisms involving nutrient sensing and signaling, known as "catabolite repression," allowing redirection of cell metabolism to maximize the consumption of an energy-efficient carbon source. Here, we report a new mechanism named "metabolic contest" for regulating the use of carbon sources without nutrient sensing and signaling. Trypanosoma brucei is a unicellular eukaryote transmitted by tsetse flies and causing human African trypanosomiasis, or sleeping sickness. We showed that, in contrast to most microorganisms, the insect stages of this parasite developed a preference for glycerol over glucose, with glucose consumption beginning after the depletion of glycerol present in the medium. This "metabolic contest" depends on the combination of 3 conditions: (i) the sequestration of both metabolic pathways in the same subcellular compartment, here in the peroxisomal-related organelles named glycosomes; (ii) the competition for the same substrate, here ATP, with the first enzymatic step of the glycerol and glucose metabolic pathways both being ATP-dependent (glycerol kinase and hexokinase, respectively); and (iii) an unbalanced activity between the competing enzymes, here the glycerol kinase activity being approximately 80-fold higher than the hexokinase activity. As predicted by our model, an approximately 50-fold down-regulation of the GK expression abolished the preference for glycerol over glucose, with glucose and glycerol being metabolized concomitantly. In theory, a metabolic contest could be found in any organism provided that the 3 conditions listed above are met., Competing Interests: The authors have declared that no competing interests exist.

Published
2021
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