Psidium acidum (DC.) Landrum (Myrtaceae): frutal de reciente cultivo en Cuba

Se registra por primera vez en Cuba Psidium acidum (DC.) Landrum (Myrtaceae), especie oriunda de América del Sur que forma parte del grupo de los guayabos ácidos. Se emplearon métodos propios de la botánica, como el trabajo con colecciones, el uso de catálogos especializados, la descripción e ilustración científica. Se discute la utilidad del fruto maduro para la alimentación humana, la acción fungicida y antioxidantes de extractos obtenidos de sus ramas y hojas, así como el potencial uso de la misma como porta-injertos de cultivares comerciales. Se ofrece una clave analítica para diferenciarla de taxones afines presentes en archipiélago cubano

Psidium acidum (DC.) Landrum (Myrtaceae): frutal de reciente cultivo en Cuba

Psidium acidum (DC.), a native species to South America that is part of the group of acid guavas, is recorded for the first time in Cuba. Botanical methods were used, such as work with collections, the use of specialized catalogs, the description and scientific illustration. The usefulness of mature fruit for human consumption, the fungicidal and antioxidants action of extracts obtained from its branches and leaves, as well as its potential use as a graft support of commercial cultivars are discussed. An analytical key is offered to differentiate it from related taxa present in the Cuban archipelago.Se registra por primera vez en Cuba Psidium acidum (DC.) Landrum (Myrtaceae), especie oriunda de América del Sur que forma parte del grupo de los guayabos ácidos. Se emplearon métodos propios de la botánica, como el trabajo con colecciones, el uso de catálogos especializados, la descripción e ilustración científica. Se discute la utilidad del fruto maduro para la alimentación humana, la acción fungicida y antioxidantes de extractos obtenidos de sus ramas y hojas, así como el potencial uso de la misma como porta-injertos de cultivares comerciales. Se ofrece una clave analítica para diferenciarla de taxones afines presentes en archipiélago cubano. &nbsp

CONTRIBUCIÓN AL ESTUDIO DE LOS BRIÓFITOS EPÍFITOS DE JUNIPERUS PHOElVlCEA L. EN LA ISLA DEL HIERRO (l. CANARIAS). I

A study of the bryophytic epiphytes of Juniperus phoenicea L present on the island of Hierro has been carried out. As a result of this investigation, a total of 23 taxa have been catalogued, of which, 5 represent new records for the island. Stations situated on the highest ground and the midmontane zone orientated S-SW, were selected, the former being richer in both flora and covering of bryophytes.En esta comunicación se aborda el estudio de los briófitos epífitos de Juniperus phoenicea L. en el Hierro y se cataloga un total de 23 táxones de los que 5 se citan por primera vez para esta isla. Se han elegido estaciones de cumbre y de piso montano seco en orientación S-SW, las primeras más ricas en flora y cobertura briofítica

Drug delivery nanosystems for the localized treatment of glioblastoma multiforme

[EN] Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood-brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood-brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.This research was funded by an Ussher start-up funding award (School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin) and the European Union’s Horizon 2020 research and innovation program under Grant agreement No. 708036.Nam, L.; Coll Merino, MC.; Erthal, L.; De La Torre-Paredes, C.; Serrano, D.; Martínez-Máñez, R.; Santos-Martinez, M.... (2018). Drug delivery nanosystems for the localized treatment of glioblastoma multiforme. Materials. 11(5). https://doi.org/10.3390/ma11050779S115Goodenberger, M. L., & Jenkins, R. B. (2012). Genetics of adult glioma. Cancer Genetics, 205(12), 613-621. doi:10.1016/j.cancergen.2012.10.009Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., … Kleihues, P. (2007). The 2007 WHO Classification of Tumours of the Central Nervous System. Acta Neuropathologica, 114(2), 97-109. doi:10.1007/s00401-007-0243-4Gutkin, A., Cohen, Z. R., & Peer, D. (2016). Harnessing nanomedicine for therapeutic intervention in glioblastoma. Expert Opinion on Drug Delivery, 13(11), 1573-1582. doi:10.1080/17425247.2016.1200557Omuro, A. (2013). Glioblastoma and Other Malignant Gliomas. JAMA, 310(17), 1842. doi:10.1001/jama.2013.280319Wang, Y., & Jiang, T. (2013). Understanding high grade glioma: Molecular mechanism, therapy and comprehensive management. Cancer Letters, 331(2), 139-146. doi:10.1016/j.canlet.2012.12.024Gallego, O. (2015). Nonsurgical treatment of recurrent glioblastoma. Current Oncology, 22(4), 273. doi:10.3747/co.22.2436Carlsson, S. K., Brothers, S. P., & Wahlestedt, C. (2014). Emerging treatment strategies for glioblastoma multiforme. EMBO Molecular Medicine, 6(11), 1359-1370. doi:10.15252/emmm.201302627Yamasaki, F., Kurisu, K., Satoh, K., Arita, K., Sugiyama, K., Ohtaki, M., … Thohar, M. A. (2005). Apparent Diffusion Coefficient of Human Brain Tumors at MR Imaging. Radiology, 235(3), 985-991. doi:10.1148/radiol.2353031338Gupta, A., Young, R. J., Shah, A. D., Schweitzer, A. D., Graber, J. J., Shi, W., … Omuro, A. M. P. (2014). Pretreatment Dynamic Susceptibility Contrast MRI Perfusion in Glioblastoma: Prediction of EGFR Gene Amplification. Clinical Neuroradiology, 25(2), 143-150. doi:10.1007/s00062-014-0289-3Fakhoury, M. (2015). Drug delivery approaches for the treatment of glioblastoma multiforme. Artificial Cells, Nanomedicine, and Biotechnology, 44(6), 1365-1373. doi:10.3109/21691401.2015.1052467Štolc, S., Jakubíková, L., & Kukurová, I. (2011). Body distribution of 11C-methionine and 18FDG in rat measured by microPET. Interdisciplinary Toxicology, 4(1). doi:10.2478/v10102-011-0010-1Galldiks, N., Dunkl, V., Kracht, L. W., Vollmar, S., Jacobs, A. H., Fink, G. R., & Schroeter, M. (2012). Volumetry of [11C]-Methionine Positron Emission Tomographic Uptake as a Prognostic Marker before Treatment of Patients with Malignant Glioma. Molecular Imaging, 11(6), 7290.2012.00022. doi:10.2310/7290.2012.00022Louis, D. N., Perry, A., Reifenberger, G., von Deimling, A., Figarella-Branger, D., Cavenee, W. K., … Ellison, D. W. (2016). The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathologica, 131(6), 803-820. doi:10.1007/s00401-016-1545-1Martínez-Garcia, M., Álvarez-Linera, J., Carrato, C., Ley, L., Luque, R., Maldonado, X., … Gil-Gil, M. (2017). SEOM clinical guidelines for diagnosis and treatment of glioblastoma (2017). Clinical and Translational Oncology, 20(1), 22-28. doi:10.1007/s12094-017-1763-6WILSON, C. B. (1964). Glioblastoma Multiforme. Archives of Neurology, 11(5), 562. doi:10.1001/archneur.1964.00460230112012Juratli, T. A., Schackert, G., & Krex, D. (2013). Current status of local therapy in malignant gliomas — A clinical review of three selected approaches. Pharmacology & Therapeutics, 139(3), 341-358. doi:10.1016/j.pharmthera.2013.05.003Westphal, M., Hilt, D. C., Bortey, E., Delavault, P., Olivares, R., Warnke, P. C., … Ram, Z. (2003). A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncology, 5(2), 79-88. doi:10.1093/neuonc/5.2.79Chamberlain, M., Rhun, E., & Taillibert, S. (2015). The future of high-grade glioma: Where we are and where are we going. Surgical Neurology International, 6(2), 9. doi:10.4103/2152-7806.151331Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., … Mirimanoff, R. O. (2005). Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma. New England Journal of Medicine, 352(10), 987-996. doi:10.1056/nejmoa043330Lee, C. Y. (2017). Strategies of temozolomide in future glioblastoma treatment. OncoTargets and Therapy, Volume 10, 265-270. doi:10.2147/ott.s120662Mun, E. J., Babiker, H. M., Weinberg, U., Kirson, E. D., & Von Hoff, D. D. (2017). Tumor-Treating Fields: A Fourth Modality in Cancer Treatment. Clinical Cancer Research, 24(2), 266-275. doi:10.1158/1078-0432.ccr-17-1117Stupp, R., Taillibert, S., Kanner, A., Kesari, S., Toms, S. A., Barnett, G. H., … Ram, Z. (2015). Tumor treating fields (TTFields): A novel treatment modality added to standard chemo- and radiotherapy in newly diagnosed glioblastoma—First report of the full dataset of the EF14 randomized phase III trial. Journal of Clinical Oncology, 33(15_suppl), 2000-2000. doi:10.1200/jco.2015.33.15_suppl.2000Bernard-Arnoux, F., Lamure, M., Ducray, F., Aulagner, G., Honnorat, J., & Armoiry, X. (2016). The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma. Neuro-Oncology, 18(8), 1129-1136. doi:10.1093/neuonc/now102Stupp, R., Hegi, M. E., Mason, W. P., van den Bent, M. J., Taphoorn, M. J., Janzer, R. C., … Mirimanoff, R.-O. (2009). Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. The Lancet Oncology, 10(5), 459-466. doi:10.1016/s1470-2045(09)70025-7Preusser, M., de Ribaupierre, S., Wöhrer, A., Erridge, S. C., Hegi, M., Weller, M., & Stupp, R. (2011). Current concepts and management of glioblastoma. Annals of Neurology, 70(1), 9-21. doi:10.1002/ana.22425FDA Grants Genentech’s Avastin Full Approval for Most Aggressive Form of Brain Cancerhttps://www.gene.com/media/press-releases/14695/2017-12-05/fda-grants-genentechs-avastin-full-approWick, W., Stupp, R., Gorlia, T., Bendszus, M., Sahm, F., Bromberg, J. E., … Van Den Bent, M. J. (2016). Phase II part of EORTC study 26101: The sequence of bevacizumab and lomustine in patients with first recurrence of a glioblastoma. Journal of Clinical Oncology, 34(15_suppl), 2019-2019. doi:10.1200/jco.2016.34.15_suppl.2019Liu, W.-Y., Wang, Z.-B., Zhang, L.-C., Wei, X., & Li, L. (2012). Tight Junction in Blood-Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances. CNS Neuroscience & Therapeutics, 18(8), 609-615. doi:10.1111/j.1755-5949.2012.00340.xRonaldson, P. T., & Davis, T. P. (2011). Targeting blood–brain barrier changes during inflammatory pain: an opportunity for optimizing CNS drug delivery. Therapeutic Delivery, 2(8), 1015-1041. doi:10.4155/tde.11.67S. Hersh, D., S. Wadajkar, A., B. Roberts, N., G. Perez, J., P. Connolly, N., Frenkel, V., … J. Kim, A. (2016). Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. Current Pharmaceutical Design, 22(9), 1177-1193. doi:10.2174/1381612822666151221150733Patel, M. M., Goyal, B. R., Bhadada, S. V., Bhatt, J. S., & Amin, A. F. (2009). Getting into the Brain. CNS Drugs, 23(1), 35-58. doi:10.2165/0023210-200923010-00003Clark, D. E. (2003). In silico prediction of blood–brain barrier permeation. Drug Discovery Today, 8(20), 927-933. doi:10.1016/s1359-6446(03)02827-7Gleeson, M. P. (2008). Generation of a Set of Simple, Interpretable ADMET Rules of Thumb. Journal of Medicinal Chemistry, 51(4), 817-834. doi:10.1021/jm701122qHervé, F., Ghinea, N., & Scherrmann, J.-M. (2008). CNS Delivery Via Adsorptive Transcytosis. The AAPS Journal, 10(3), 455-472. doi:10.1208/s12248-008-9055-2Van Tellingen, O., Yetkin-Arik, B., de Gooijer, M. C., Wesseling, P., Wurdinger, T., & de Vries, H. E. (2015). Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resistance Updates, 19, 1-12. doi:10.1016/j.drup.2015.02.002Ostermann, S. (2004). Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients. Clinical Cancer Research, 10(11), 3728-3736. doi:10.1158/1078-0432.ccr-03-0807Laquintana, V., Trapani, A., Denora, N., Wang, F., Gallo, J. M., & Trapani, G. (2009). New strategies to deliver anticancer drugs to brain tumors. Expert Opinion on Drug Delivery, 6(10), 1017-1032. doi:10.1517/17425240903167942Zhan, C., Gu, B., Xie, C., Li, J., Liu, Y., & Lu, W. (2010). Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances paclitaxel anti-glioblastoma effect. Journal of Controlled Release, 143(1), 136-142. doi:10.1016/j.jconrel.2009.12.020Kondo, Y., Kondo, S., Tanaka, Y., Haqqi, T., Barna, B. P., & Cowell, J. K. (1998). Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. Oncogene, 16(17), 2243-2248. doi:10.1038/sj.onc.1201754Wang, P. P., Frazier, J., & Brem, H. (2002). Local drug delivery to the brain. Advanced Drug Delivery Reviews, 54(7), 987-1013. doi:10.1016/s0169-409x(02)00054-6De Souza, R., Zahedi, P., Allen, C. J., & Piquette-Miller, M. (2010). Polymeric drug delivery systems for localized cancer chemotherapy. Drug Delivery, 17(6), 365-375. doi:10.3109/10717541003762854Wolinsky, J. B., Colson, Y. L., & Grinstaff, M. W. (2012). Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers. Journal of Controlled Release, 159(1), 14-26. doi:10.1016/j.jconrel.2011.11.031Chakroun, R. W., Zhang, P., Lin, R., Schiapparelli, P., Quinones-Hinojosa, A., & Cui, H. (2017). Nanotherapeutic systems for local treatment of brain tumors. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 10(1), e1479. doi:10.1002/wnan.1479Mathios, D., Kim, J. E., Mangraviti, A., Phallen, J., Park, C.-K., Jackson, C. M., … Lim, M. (2016). Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM. Science Translational Medicine, 8(370), 370ra180-370ra180. doi:10.1126/scitranslmed.aag2942Chaichana, K. L., Pinheiro, L., & Brem, H. (2015). Delivery of local therapeutics to the brain: working toward advancing treatment for malignant gliomas. Therapeutic Delivery, 6(3), 353-369. doi:10.4155/tde.14.114Patchell, R. A., Regine, W. F., Ashton, P., Tibbs, P. A., Wilson, D., Shappley, D., & Young, B. (2002). Journal of Neuro-Oncology, 60(1), 37-42. doi:10.1023/a:1020291229317Hassenbusch, S. J., Nardone, E. M., Levin, V. A., Leeds, N., & Pietronigro, D. (2003). Stereotactic Injection of DTI-015 into Recurrent Malignant Gliomas: Phase I/II Trial. Neoplasia, 5(1), 9-16. doi:10.1016/s1476-5586(03)80012-xBoiardi, A., Eoli, M., Salmaggi, A., Zappacosta, B., Fariselli, L., Milanesi, I., … Silvani, A. (2001). Journal of Neuro-Oncology, 54(1), 39-47. doi:10.1023/a:1012510513780Lidar, Z., Mardor, Y., Jonas, T., Pfeffer, R., Faibel, M., Nass, D., … Ram, Z. (2004). Convection-enhanced delivery of paclitaxel for the treatment of recurrent malignant glioma: a Phase I/II clinical study. Journal of Neurosurgery, 100(3), 472-479. doi:10.3171/jns.2004.100.3.0472Bruce, J. N., Fine, R. L., Canoll, P., Yun, J., Kennedy, B. C., Rosenfeld, S. S., … DeLaPaz, R. L. (2011). Regression of Recurrent Malignant Gliomas With Convection-Enhanced Delivery of Topotecan. Neurosurgery, 69(6), 1272-1280. doi:10.1227/neu.0b013e3182233e24Carpentier, A., Metellus, P., Ursu, R., Zohar, S., Lafitte, F., Barrie, M., … Carpentier, A. F. (2010). Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. Neuro-Oncology, 12(4), 401-408. doi:10.1093/neuonc/nop047Bogdahn, U., Hau, P., Stockhammer, G., Venkataramana, N. K., Mahapatra, A. K., … Suri, A. (2010). Targeted therapy for high-grade glioma with the TGF- 2 inhibitor trabedersen: results of a randomized and controlled phase IIb study. Neuro-Oncology, 13(1), 132-142. doi:10.1093/neuonc/noq142Iwamoto, F. M., Lamborn, K. R., Robins, H. I., Mehta, M. P., Chang, S. M., Butowski, N. A., … Fine, H. A. (2010). Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro-Oncology, 12(8), 855-861. doi:10.1093/neuonc/noq025Brem, S., Tyler, B., Li, K., Pradilla, G., Legnani, F., Caplan, J., & Brem, H. (2007). Local delivery of temozolomide by biodegradable polymers is superior to oral administration in a rodent glioma model. Cancer Chemotherapy and Pharmacology, 60(5), 643-650. doi:10.1007/s00280-006-0407-2Recinos, V. R., Tyler, B. M., Bekelis, K., Sunshine, S. B., Vellimana, A., Li, K. W., & Brem, H. (2010). Combination of Intracranial Temozolomide With Intracranial Carmustine Improves Survival When Compared With Either Treatment Alone in a Rodent Glioma Model. Neurosurgery, 66(3), 530-537. doi:10.1227/01.neu.0000365263.14725.39Storm, P. B., Moriarity, J. L., Tyler, B., Burger, P. C., Brem, H., & Weingart, J. (2002). Journal of Neuro-Oncology, 56(3), 209-217. doi:10.1023/a:1015003232713Scott, A. W., Tyler, B. M., Masi, B. C., Upadhyay, U. M., Patta, Y. R., Grossman, R., … Cima, M. J. (2011). Intracranial microcapsule drug delivery device for the treatment of an experimental gliosarcoma model. Biomaterials, 32(10), 2532-2539. doi:10.1016/j.biomaterials.2010.12.020Kim, G. Y., Tyler, B. M., Tupper, M. M., Karp, J. M., Langer, R. S., Brem, H., & Cima, M. J. (2007). Resorbable polymer microchips releasing BCNU inhibit tumor growth in the rat 9L flank model. Journal of Controlled Release, 123(2), 172-178. doi:10.1016/j.jconrel.2007.08.003Masi, B. C., Tyler, B. M., Bow, H., Wicks, R. T., Xue, Y., Brem, H., … Cima, M. J. (2012). Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model. Biomaterials, 33(23), 5768-5775. doi:10.1016/j.biomaterials.2012.04.048Li, X., Tsibouklis, J., Weng, T., Zhang, B., Yin, G., Feng, G., … Mikhalovsky, S. V. (2016). Nano carriers for drug transport across the blood–brain barrier. Journal of Drug Targeting, 25(1), 17-28. doi:10.1080/1061186x.2016.1184272Mangraviti, A., Gullotti, D., Tyler, B., & Brem, H. (2016). Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies. Journal of Controlled Release, 240, 443-453. doi:10.1016/j.jconrel.2016.03.031Torchilin, V. P. (2009). Passive and Active Drug Targeting: Drug Delivery to Tumors as an Example. Handbook of Experimental Pharmacology, 3-53. doi:10.1007/978-3-642-00477-3_1Rippe, B., Rosengren, B.-I., Carlsson, O., & Venturoli, D. (2002). Transendothelial Transport: The Vesicle Controversy. Journal of Vascular Research, 39(5), 375-390. doi:10.1159/000064521Hobbs, S. K., Monsky, W. L., Yuan, F., Roberts, W. G., Griffith, L., Torchilin, V. P., & Jain, R. K. (1998). Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment. Proceedings of the National Academy of Sciences, 95(8), 4607-4612. doi:10.1073/pnas.95.8.4607Lammers, T., Kiessling, F., Hennink, W. E., & Storm, G. (2012). Drug targeting to tumors: Principles, pitfalls and (pre-) clinical progress. Journal of Controlled Release, 161(2), 175-187. doi:10.1016/j.jconrel.2011.09.063Danhier, F. (2016). To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? Journal of Controlled Release, 244, 108-121. doi:10.1016/j.jconrel.2016.11.015Petros, R. A., & DeSimone, J. M. (2010). Strategies in the design of nanoparticles for therapeutic applications. Nature Reviews Drug Discovery, 9(8), 615-627. doi:10.1038/nrd2591Chouly, C., Pouliquen, D., Lucet, I., Jeune, J. J., & Jallet, P. (1996). Development of superparamagnetic nanoparticles for MRI: effect of particle size, charge and surface nature on biodistribution. Journal of Microencapsulation, 13(3), 245-255. doi:10.3109/02652049609026013OWENSIII, D., & PEPPAS, N. (2006). Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. International Journal of Pharmaceutics, 307(1), 93-102. doi:10.1016/j.ijpharm.2005.10.010Salvador-Morales, C., Zhang, L., Langer, R., & Farokhzad, O. C. (2009). Immunocompatibility properties of lipid–polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials, 30(12), 2231-2240. doi:10.1016/j.biomaterials.2009.01.005Zhan, C., & Lu, W. (2012). The Blood-Brain/Tumor Barriers: Challenges and Chances for Malignant Gliomas Targeted Drug Delivery. Current Pharmaceutical Biotechnology, 13(12), 2380-2387. doi:10.2174/138920112803341798Steiniger, S. C. J., Kreuter, J., Khalansky, A. S., Skidan, I. N., Bobruskin, A. I., Smirnova, Z. S., … Gelperina, S. E. (2004). Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. International Journal of Cancer, 109(5), 759-767. doi:10.1002/ijc.20048Wohlfart, S., Khalansky, A. S., Bernreuther, C., Michaelis, M., Cinatl, J., Glatzel, M., & Kreuter, J. (2011). Treatment of glioblastoma with poly(isohexyl cyanoacrylate) nanoparticles. International Journal of Pharmaceutics, 415(1-2), 244-251. doi:10.1016/j.ijpharm.2011.05.046Zanotto-Filho, A., Coradini, K., Braganhol, E., Schröder, R., de Oliveira, C. M., Simões-Pires, A., … Moreira, J. C. F. (2013). Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment. European Journal of Pharmaceutics and Biopharmaceutics, 83(2), 156-167. doi:10.1016/j.ejpb.2012.10.019Gao, H. (2016). Perspectives on Dual Targeting Delivery Systems for Brain Tumors. Journal of Neuroimmune Pharmacology, 12(1), 6-16. doi:10.1007/s11481-016-9687-4Pinto, M. P., Arce, M., Yameen, B., & Vilos, C. (2017). Targeted brain delivery nanoparticles for malignant gliomas. Nanomedicine, 12(1), 59-72. doi:10.2217/nnm-2016-0307Fang, C., Wang, K., Stephen, Z. R., Mu, Q., Kievit, F. M., Chiu, D. T., … Zhang, M. (2015). Temozolomide Nanoparticles for Targeted Glioblastoma Therapy. ACS Applied Materials & Interfaces, 7(12), 6674-6682. doi:10.1021/am5092165Ke, W., Shao, K., Huang, R., Han, L., Liu, Y., Li, J., … Jiang, C. (2009). Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials, 30(36), 6976-6985. doi:10.1016/j.biomaterials.2009.08.049Xin, H., Jiang, X., Gu, J., Sha, X., Chen, L., Law, K., … Fang, X. (2011). Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials, 32(18), 4293-4305. doi:10.1016/j.biomaterials.2011.02.044Zhang, B., Wang, H., Liao, Z., Wang, Y., Hu, Y., Yang, J., … Jiang, X. (2014). EGFP–EGF1-conjugated nanoparticles for targeting both neovascular and glioma cells in therapy of brain glioma. Biomaterials, 35(13), 4133-4145. doi:10.1016/j.biomaterials.2014.01.071Zhang, P., Hu, L., Yin, Q., Feng, L., & Li, Y. (2012). Transferrin-Modified c[RGDfK]-Paclitaxel Loaded Hybrid Micelle for Sequential Blood-Brain Barrier Penetration and Glioma Targeting Therapy. Molecular Pharmaceutics, 9(6), 1590-1598. doi:10.1021/mp200600tMa, D. (2014). Enhancing endosomal escape for nanoparticle mediated siRNA delivery. Nanoscale, 6(12), 6415. doi:10.1039/c4nr00018hShim, M. S., & Kwon, Y. J. (2012). Stimuli-responsive polymers and nanomaterials for gene delivery and imaging applications. Advanced Drug Delivery Reviews, 64(11), 1046-1059. doi:10.1016/j.addr.2012.01.018Zarebkohan, A., Najafi, F., Moghimi, H. R., Hemmati, M., Deevband, M. R., & Kazemi, B. (2015). Synthesis and characterization of a PAMAM dendrimer nanocarrier functionalized by SRL peptide for targeted gene delivery to the brain. European Journal of Pharmaceutical Sciences, 78, 19-30. doi:10.1016/j.ejps.2015.06.024Hynynen, K., McDannold, N., Vykhodtseva, N., & Jolesz, F. A. (2001). Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits. Radiology, 220(3), 640-646. doi:10.1148/radiol.2202001804Nance, E., Timbie, K., Miller, G. W., Song, J., Louttit, C., Klibanov, A. L., … Price, R. J. (2014). Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood − brain barrier using MRI-guided focused ultrasound. Journal of Controlled Release, 189, 123-132. doi:10.1016/j.jconrel.2014.06.031Mead,

Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid arthritis in daily practice

[Objectives]: We aimed to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. [Methods]: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). [Results]: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). [Conclusion]: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.Peer Reviewe

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Enteritis secundaria a nivolumab, una causa creciente de diarrea

La inmunoterapia es una herramienta cada vez más utilizada en el campo de la oncología. Conviene conocerla debido a sus crecientes usos, entre los que se incluye el tratamiento de tumores del aparato digestivo (hepatocarcinoma1, adenocarcinoma colorrectal con alta inestabilidad en microsatelites2) así como por las reacciones adversas que con elevada frecuencia afectan al tubo digestivo. Presentamos el caso de un varón de 74 años, con antecedentes personales de enfermedad pulmonar obstructiva crónica (EPOC) y melanoma con metástasis pulmonares. Debido a estas patologías tomaba de manera habitual inhaladores de salbutamol y había estado en tratamiento con nivolumab, suspendido hacía cuatro meses tras conseguir una respuesta radiológica completa de las metástasis pulmonares. El paciente refería cuadro diarreico de un mes de evolución, consistente en tres a cuadro deposiciones (Bristol 5-6) sin productos patológicos, que afectaban el descanso nocturno, asociaban molestias centroabdominales intermitentes y pérdida de peso de unos 3-4 kg. No había ingerido alimentos crudos, antibióticos o nuevas medicaciones. Tampoco había convivientes con la misma sintomatología ni había realizado viajes al extranjero. Negaba cualquier otra sintomatología y antecedentes familiares de interés. La exploración física era anodina a excepción de unas ligeras molestias a la palpación profunda en mesogastrio..