Roldan-Fidalgo A.,Autonomous University of Madrid |
Martin Saldana S.,Foundation for Biomedical Research |
Trinidad A.,Autonomous University of Madrid |
Olmedilla-Alonso B.,Institute of Food Science |
And 3 more authors.
Experimental and Toxicologic Pathology | Year: 2016
Introduction: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. Aim: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity. Materials and Methods: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 μM) and to 25 μM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min, 1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy. Results: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 μM. In vivo study: Intratympanic lutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats. Conclusions: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result. © 2016 Elsevier GmbH. Source
De Pablo A.,Foundation University |
Bogoi R.,Foundation University |
Bejarano I.,Foundation for Biomedical Research |
Toro C.,Charles III University of Madrid |
And 5 more authors.
AIDS Research and Human Retroviruses | Year: 2016
The p21/CDKN1A protein has been described in vitro as well as in a small subset of patients as a restriction factor for HIV infection. We evaluated p21/CDKN1A mRNA expression on CD4+ T cells from HIV-infected individuals with two outcomes (18 elite controllers and 28 viremic progressors). Our results show broad interindividual variation in this factor, which is unrelated to the patient's phenotype. Considering the gene's genetic surroundings in chromosome 6, such as HLA genotype and single nucleotide polymorphisms (SNPs), there was a positive association with carrying HLA-B2705 alleles and the rs733590 SNP. Thus, this natural variation of p21/CDKN1A alone does not appear to be a prognostic indicator of effective viral control in vivo and other factors must be considered. © Mary Ann Liebert, Inc. 2016. Source
News Article | December 3, 2007
Now that the deal between Vivendi and Activision has been officially announced, it looks like the former will take two-thirds control in the popular developer and be able to compete more effectively against the video game industry's de facto big shot--EA. And while the $1.7 billion will allow Vivendi to become a more "complete" organization that can offer a wide array of games for people on all platforms, I just can't see how this will benefit any consumers. Sure, the merger between Vivendi and Activision will finally create a competitor for the behemoth that is EA and with Activision's current streak of 74 percent growth since 2003 as compared to EA's paltry 25 percent, it's certainly possible that the former could overtake the latter in terms of size within the next decade. But is an environment where two major video game developers control a significant stake of the market really beneficial to consumers? Unfortunately, the answer is no. EA acquired small developers for one reason: to improve its own game lineup without being forced to create unique titles on its own. And to make matters worse, most of the game franchises it bought were ruined after a few years with EA at the helm. In fact, EA has averaged at least 1.2 acquisitions per year since 1995: Manley & Associates (1996); Maxis (1997); Westwood and Tiburon (1998); Kesmai (1999); Dreamworks Interactive (2000); former Sega Sports studio Black Box (2002); Studio 33 (2003); NuFX (2003); Criterion (2005); JAMDAT Mobile (2006; Mythic (2006); DICE (2006); and Bioware/Pandemic (2007). Save for the latest acquisition, can it be said that EA improved any of these swallowed up studios? If you believe it has, I think you're mistaken. Upon acquiring new studios, EA has taken a successful franchise and doled it out to studios all over North America to create sequel after sequel. And each time the sequel hits store shelves, the allure of the first title quickly gives way to a sense of contempt for the entire franchise. Is that really what we want from Activision and Vivendi? Interestingly enough, Will Wright--the creator of SimCity and a victim of the "buy and reproduce" mentality of the video game industry--chimed in on the subject of sequels. In an interview with German site Stern, Wright was asked about his thoughts on sequels and the following to say: "One would rather play it safe than be creative. Still, this seems to work. But for how much longer? Besides, there are simply too many games on the market. Lots of bad games are coming out because of this." But it's not just Will Wright who believes creativity is what will drive this industry forward and create a better environment for gamers. In an interview with GameIndustry.biz last year, a representative from Ubisoft -- a company partially owned by EA -- explained that "it would be dangerous for a company like Ubisoft to get together too much with a company like EA, because it could kill creativity - and in [the game] industry...that's key." But if all of these "experts" feel this way, why doesn't EA, Vivendi and Activision feel the same way? Is it because the almighty dollar is far more important to these companies than doing what is right for gamers? You better believe it. A quick glance at the current state of the video game industry will immediately yield one fact: the most innovative games are not coming from huge developers, they're coming from small developers with titles like Katamari Damacy. On the other hand, it's the larger developers like EA and now, Vivendi-Activision that create derivative gameplay that makes us all wish for the days of small studios creating games out of a love for video games and not a profit. Unfortunately, the vast majority of video games are developed in a top-floor office by a group of suits who think they know exactly how to create a game that will sell well. And although some developers may have fresh ideas that will push this industry forward, most of those ideas are turned away and called "too costly" or "not commercial enough." And while this may still help these large developers enjoy record profits, it won't last forever. And once the majority of gamers wake up and realize they are victims to a commercial enterprise and not the beneficiaries of innovative video game titles, I think we will see a major shift in the way games are developed.
Panzee the chimpanzee was a skilled communicator that could tell untrained humans where to find hidden food by using gestures and vocalizations. Austin the chimp was particularly adept with a computer, and scientists have been scanning the animal's genome for clues to its unusual cognitive abilities. Both apes lived at a language-research centre at Georgia State University in Atlanta, and both died several years ago — but they will live on in an online database of brain scans and behavioural data from nearly 250 chimpanzees. Researchers hope to combine this trove, now in development, with a biobank of chimpanzee brains to enable scientists anywhere in the world to study the animals’ neurobiology. This push to repurpose old data is especially timely now that the US National Institutes of Health (NIH) has decided to retire its remaining research chimpanzees. The agency decommissioned more than 300 animals in 2013, but kept 50 available for research in case of a public-health emergency. Following an 18 November decision, this remaining population will also be sent to sanctuaries in the coming years. The NIH also hopes to retire another 82 chimps that it supports but does not own, says director Francis Collins. “We were on a trajectory toward zero, and today’s the day we’re at zero,” says Jeffrey Kahn, a bioethicist at Johns Hopkins University in Baltimore, Maryland, who led a 2011 study on the NIH chimp colony for the Institute of Medicine. The NIH’s latest move, along with a decision in June by the US Fish and Wildlife Service to give research chimps endangered-species protections, effectively ends the possibility of biomedical research on the animals in the United States. The retirement of the NIH chimps will also end non-invasive studies on the 139 NIH-owned animals at the University of Texas MD Anderson Cancer Center primate facility in Bastrop. Its director, Christian Abee, says that researchers have published more than 50 behavioural studies since 2012 using these animals. “There is no other alternative for cognitive research in chimpanzees,” he says. That makes the NIH-funded chimp database all the more important. “This is a very unique window of opportunity to make sure that there’s a legacy and a contribution from the lives they have lived,” says project leader Chet Sherwood, a biological anthropologist at George Washington University in Washington DC. In the next few months, Sherwood’s team plans to launch a website with a database for researchers and an educational component for the public. The site will eventually include existing data on the chimps’ performance in behaviour and personality tests, scans of the primates’ brain structure and activity, and their pedigrees and some genetic information. Sherwood and his colleagues plan to model the website on that of the Human Connectome Project, an open-access collection of brain scans from 1,200 individuals that researchers can use to study the links between brain structure and activity and human traits. The team is also collaborating with the Allen Brain Institute in Seattle, Washington, to create an atlas of gene expression in the chimp brain. Researchers who want to study chimp brains in more detail can request tissue and blood samples from the team, which has nearly 250 preserved organs stored at facilities in Washington DC and Atlanta. But some scientists and advocates worry about the consequences of losing access to research chimps. Frankie Trull, director of the Foundation for Biomedical Research in Washington DC, which advocates for animal research, says that the US government may regret its decision if a public-health threat emerges that would be best studied in chimpanzees. Others caution that the dwindling number of research animals will make it difficult to develop therapies — such as vaccines against Ebola — for wild chimps, which would help both the animals and human beings. In the meantime, the NIH is struggling to find homes for its newly retired chimps. By law, retired animals are sent to a federal sanctuary known as Chimp Haven in Keithville, Louisiana, but that facility has only 25 places available now. Nearly 310 NIH-owned animals need to be resettled, and Collins says that the agency is still evaluating its options — a situation that worries lawmakers. On 20 November, two members of Congress sent the NIH a letter asking the agency for its plan to rehome the remaining chimps. “We want to make sure that for the sake of taxpayers and these much-abused chimpanzees, these delays are overcome immediately,” they wrote. Although retired, the apes of Chimp Haven may one day re-enter research labs — posthumously. Sherwood’s team is drafting an agreement with the sanctuary to obtain the animals’ brains when they die; it also hopes to acquire organs from chimps in zoos and research facilities. “You can imagine 20 years from now, this ageing population won’t be here,” he says. “If we weren’t making the efforts today, there wouldn’t be a way to study neurobiology in chimpanzees.”
Martinez-Miguel P.,Foundation for Biomedical Research |
Martinez-Miguel P.,Foundation for Biomedical Research |
de Sequera P.,Nephrology Section |
Albalate M.,Nephrology Section |
And 13 more authors.
International Journal of Artificial Organs | Year: 2015
Purpose: The biocompatibility of dialyzers may influence the inflammatory state of hemodialysis patients. This study compares the effect of a high-flux polynephron membrane with other high-flux membranes, helixone and polyamide, on some inflammation biomarkers based on the analysis of circulating mononuclear cells (MC). Methods: The study included 47 patients on hemodialysis with helixone and polyamide; 9 formed the control group, without changes in their dialyzers throughout the study, and 38 formed the intervention group, in which their dialyzers were replaced by polynephron. In both groups, blood samples were taken at the beginning of the study before and after hemodialysis session, and at the end of the study 4 months later. In each extraction, biochemical parameters were determined, and MC isolated using Ficoll gradient. Production of reactive oxygen species and the percentage of activated MC (CD14+CD16+) were measured by flow cytometry, and protein levels of heat-shock proteins (Hsp70/Hsp90) studied by Western blot. Results: After 1 hemodialysis session with different membranes, no significant differences were observed in the different parameters considered. After 4 months of dialysis with polynephron, a significant reduction in the percentage of CD14+CD16+ and in the β2-microglobulin reduction ratio were found, with respect to helixone and polyamide, without changes in the other parameters analyzed. Conclusions: The use of polynephron for 4 months reduces the percentage of CD14+CD16+ compared to helixone and polyamide, suggesting a better profile regarding activation of the inflammatory response. These findings could be explained by a better biocompatibility or an increased reduction of medium-sized toxic molecules. © 2015 Wichtig Publishing. Source