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Avastin (bevacizumab) and Lucentis (ranibizumab injection), two drugs used to treat age-related macular degeneration (AMD)—the leading cause of vision loss and blindness in older Americans—were compared head-to-head for the first time in a two-year clinical trial. In conducting the Comparison of AMD Treatment Trials (CATT), NEI researchers and their collaborators found that Avastin and Lucentis were equivalent in treating AMD. In AMD’s advanced stages, abnormal blood vessels leak fluid and blood into the macula, the central part of the retina that allows perception of fine visual detail, and obscure vision. Avastin and Lucentis block the growth of abnormal blood vessels and leakage of fluid from the vessels.
Patients in the CATT trial were assigned to four treatment groups defined by drug (Avastin or Lucentis) and dosing regimen (monthly or as needed). At two years, visual acuity with monthly treatment was slightly better than with as-needed dosing, regardless of the drug. Overall, after two years, two-thirds of patients had 20/40 vision or better, compared with only 15 percent of patients retaining similar visual acuity with previous treatments. (NIH authors: M. Redford, F.L. Ferris; Ophthalmology DOI: 10.1016/j.ophtha.2012.03.053)
A new technique for improving delivery of stem cells, developed by NIH researchers and others, may lead to better and faster tissue repair. Using noninvasive pulsed focused ultrasound (pFUS), in which high amounts of energy are delivered to a treatment site without affecting the surrounding tissue, the researchers enhanced the delivery of transplant cells in rodents. Energy generated by noninvasive pFUS stimulates tissue at the treatment site to produce mediators such as cytokines, chemokines, and growth factors. Normally, the production of these mediators is enhanced only during inflammation or injury. Because transplanted stem cells have receptors for these chemical agents, more chemicals attract more transplant cells to the desired site. By increasing the concentration of naturally produced chemical agents, the researchers saw eight to 10 times as many transplanted bone marrow stromal cells in a pFUS-treated rodent kidney than in a nontreated kidney. The use of pFUS to improve transplant cell delivery is a breakthrough in regenerative medicine with implications for sports medicine and military medicine. (NIH authors: A. Ziadloo, S.R. Burks, E.M. Gold, B.K. Lewis, A. Chaudhry, M.J. Merino, J.A. Frank; Stem Cells 30:1216–1227, 2012)
For years, researchers have known that obesity, type 2 diabetes, and inflammation are linked, but have not fully understood how. A study done by NIAAA researchers and others revealed that natural killer T (NKT) cells, essential to the human immune system, are a key piece of the puzzle. The researchers injected mice that were fed high-fat diets with alpha-galactosylceramide, a lipid known to specifically activate NKT cells. The injected mice exhibited decreased tissue inflammation, decreased insulin resistance, and increased glucose tolerance. Thus, though the mice were being fed a high-fat diet, their metabolic response was closer to that of mice being fed a healthier diet. The researchers plan to next alter the regimen of lipid treatment to see whether they can induce an even better effect in animals and identify compounds in foods that naturally activate NKT cells in humans. Their ultimate goal is to identify specific foods that obese people with diabetes could eat to achieve the positive effects seen in mice. (NIH authors: B. Gao; J Biol Chem 287:13561–13571, 2012)
Television viewing and unhealthy eating habits in U.S. adolescents appear to be linked, according to a study performed by NIH scientists and others. The study authors used data from the 2009-2010 Health Behavior in School-Aged Children Study, a nationwide survey of 12,642 U.S. students in grades 5 through 10. Television viewing time was found to be associated with decreased consumption of fruit or vegetables daily and increased consumption of candy and soda daily, skipping breakfast at least one day per week, and eating at a fast-food restaurant at least one day per week. Further research is needed to clarify the independent contributions of TV viewing, food advertising, and TV snacking on dietary intake in U.S. adolescents. (NIH authors: L.M. Lipsky, R.J. Iannotti; Arch Pediatr Adolesc Med 166:465-472, 2012)
Poor-quality antimalarial drugs lead to inadequate treatment and drug resistance and pose a threat to vulnerable populations. By studying survey data of the malaria drugs available across Southeast Asia and sub-Saharan Africa, NIH researchers found that from 20 to 42 percent are either poor quality or fake. The researchers also found that antimalarial drugs are widely distributed and self-prescribed, correctly or incorrectly, in the regions surveyed. Facilities to monitor the quality of antimalarial drugs are lacking, as are consumer and health-worker knowledge about the therapies. Of particular concern are signs of resistance to artemisinin derivatives, the most effective drugs against malaria, in western Cambodia. The findings indicate the need for a series of interventions to better define and eliminate poor-quality antimalarial drugs. (NIH authors: G.M.L. Nayyar, J.G. Breman, J. Herrington; Lancet Infect Dis 12:488–496, 2012)
Steven Roberts, NIEHS
DNA mutations are thought to be rare events that occur randomly and over time, but NIEHS researchers have identified DNA regions in yeast and in some cancers that have a disproportionately high number of mutations that arose simultaneously. In yeast, the clusters are produced by exposure to environmental toxins; in cancers, they are produced through typical biochemical processes.
NIEHS researchers and their collaborators have identified DNA regions in yeast and in some cancers that have a disproportionately high number of mutations. The findings represent an exception to the traditional view that mutations accumulate over time, and may explain one of the mechanisms behind cancer development. Team members subjected yeast to continuous damage by growing them in media containing the carcinogen methyl methanesulfonate (MMS). Normally, mutations occur haphazardly throughout the genome. But the researchers found that for approximately 70 yeast cells, certain DNA clusters contained more mutations than the rest of the genome. These clusters also exhibited a very unusual pattern, suggesting they were formed simultaneously in stretches of abnormally long single-stranded DNA.
The researchers next found that over half of 32 human tumor types examined had mutation clusters. But the cause of the mutation clusters wasn’t environmental damage as it was in yeast. The DNA sequence surrounding clustered mutations suggested that specific proteins called apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytosine deaminases, which inactivate viruses attacking the body, are also somehow damaging DNA. The study results suggest that antiviral drugs capable of stimulating APOBEC genes should be studied for potential long-term effects connected with enhanced mutagenesis. (NIH authors: S.A. Roberts, J. Sterling, C. Thompson, S. Harris, L.J. Klimczak M.A. Resnick, D.A. Gordenin; Molec Cell 46:424–435, 2012)
NIH scientists and their collaborators have identified a new human immunodeficiency virus (HIV)–suppressing protein in the blood of people infected with the virus. In laboratory studies, the chemokine CXCL4 binds to HIV and thereby prevents it from attaching to or entering a human cell. Previously, four chemokines were known to function as HIV inhibitors. These chemokines, as well as CXCL4, may regulate the level of virus replication in infected individuals and thus the pace at which HIV disease progresses. According to the researchers, the site where CXCL4 binds to the outer coat of HIV seems to be different from other known vulnerable sites targeted by HIV-blocking antibodies and drugs. The researchers aim to better understand CXCL4’s role in HIV disease and to determine whether the chemokine has a protective effect not only in laboratory studies, but also in people. (NIH authors: D.J. Auerbach, Y. Lin, H. Miao, R. Cimbro, M.J. DiFiore, M.E. Gianolini, A.S. Fauci, P. Lusso; Proc Natl Acad Sci USA 109:9569–9574, 2012)
Viewing a five-minute video can remove memories of past drug use in former heroin addicts and ease cravings, according to a study done by NIDA researchers and others. Sixty-six people battling heroin addiction watched a video of people smoking and injecting heroin, which served as a quick reminder of past drug abuse. The study subjects then participated in “extinction sessions,” in which they watched more drug-related videos and slideshows and handled fake heroin. Time between the reminder and the extinction sessions was varied: some people waited 10 minutes, others waited six hours. The researchers found that people whose memories were primed with the drug reminder 10 minutes before extinction reported less craving for heroin after seeing drug cues than did people who hadn’t received the reminder. In contrast, people who waited six hours before undergoing the extinction did not get the same effect. The results suggest that there’s something important happening in the 10-minute window right after the reminder. Further investigation is needed to clarify whether the effects persists under normal circumstances. (NIH authors: D.H. Epstein, Y. Shaham; Science 336:241–245, 2012)