Science Weekly: A taste of things to come, and Darwin’s dogs

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We discuss what 2010 will hold for Nasa, the LHC and disappointed climate change activists. Plus, Emma Townshend explains how dogs helped inspire Darwin

Fundamentals of the Bioscience Industry Course

Target Health is pleased to announce that Dr. Jules T. Mitchel is one of the Course Directors of The Fundamentals of the Bioscience Industry program at SUNY Stony Brook. The course, which will be given in both Manhattan and Stony Brook, provides life scientists with a comprehensive introduction to the bioscience business environment. This innovative, 15-week program provides participants with a comprehensive introduction to the complexities of the bioscience business environment including current business models, product development cycles, technology management, regulatory issues, and future trends in the life sciences.

Participants in the program gain valuable insights that help guide their careers and expand career options. Classes begin January 27, 2010. Visit www.fobip.org for more information or contact Kate Posnanski at kposnanski@notes.cc.sunysb.edu.

For more information about Target Health and our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website at www.targethealth.com

Artificial Red Blood Cells for Drug Delivery

These novel particles could make red cells last longer in the blood. Since the 1950s, researchers have been trying to mimic the abilities of red 1) ___ cells. These flexible discs carry oxygen throughout the body, squeezing through the smallest capillaries to do so. But the physical characteristics of red blood cells, including their doubly concave shape, have made them difficult to copy with precision. In research, recently published in the Proceedings of the National Academy of Sciences, a group specializing in drug delivery has found a way to create biodegradable, biocompatible particles with the size, shape, and flexibility of red blood 2) ___. The group believes these artificial cells might be particularly effective not just for carrying oxygen but also as therapeutic and imaging agents. People have made over a thousand different polymers of different sizes for drug delivery. But if you look at them all together, they represent the synthetic world; the particles are nice and spherical. If you look at the biological world, nature uses all kinds of particles for delivering its own goods. Bacteria, cells, viruses are all designed to perform very specific 3) ___ functions. To create the synthetic cells, researchers at the University of Michigan, start with spherical particles made of a common 4) ___ called polylactic-co-glycolic acid (PLGA), a compound known for its biocompatible and biodegradable properties. They expose the spheres to rubbing alcohol, which causes them to deflate and collapse into the dimpled shape of a red blood cell. The hard PLGA particle acts as a mold, around which the researchers can deposit layer after layer of proteins. They crosslink the proteins to get them to hold to the PLGA, then dissolve the rigid inner structure. The result is a soft, flexible protein shell the size and shape of a red blood cell. The researchers can also vary the protein coatings depending, for example adding hemoglobin, which could carry 5) ___. So far, it has been shown, that the particles are 6) ___ enough to compress and flow through capillary-sized tubes, and can be infused with drugs at just about every stage of the process. Researchers have also encapsulated iron-oxide nanoparticles in the synthetic cells, creating a potential contrast agent for MRIs. One can imagine putting these particles into the blood and using them to visualize blood flow. There’s an increasing appreciation about how the shape of particles is important for a variety of different things, like the hydrodynamics of particles inside fluid, or how different biological entities interact with them. Such flexible, potentially long-lasting particles hold great potential for 7) ___ delivery. Scientists still need to see whether the synthetic cells can stand up to the most difficult test: remaining in circulation. Proving that the particles remain in the bloodstream and do not prompt an immune attack is a critical step that will require testing in animals. “Back in 1966, I made similar [particles] that can change in shape and in size,” says artificial blood researcher Thomas Chang from McGill University in Quebec, Canada. Those cells, he says, could also squeeze through capillary tubes and were about the same size as red blood cells. The problem was that even synthetic cells one-eighth of the size of regular blood cells were purged from the blood within 30 seconds. “The main thing is to show that they remain in 8) ___,” Chang says. Even the most advanced synthetic particles get cleared out of the blood incredibly rapidly. “The longest circulating nanoparticle ever, lasted about 24 hours, so there’s a need for developing an approach to something that can circulate in the bloodstream for a long period of 9) ___,” says Jeffrey Karp, a Harvard-MIT professor of health science and technology. But the new research could be a big step in that direction if the body keeps the synthetic cells circulating for as long as two to three months, like real red blood cells. The next step will be 10) ___ testing. Researchers want to look into other ways to mimic nature’s delivery methods. They’ve started with red blood cells, but there are many others that might be of interest, like viruses and bacteria. There is the synthetic world on one side, and the biological world on the other, and scientists want to bridge the gap as best they can between these two extremes. Source: MIT Technology Review

ANSWERS: 1) blood; 2) cells; 3) delivery; 4) polymer; 5) oxygen; 6) flexible; 7) drug; 8) circulation; 9) time; 10) animal

Public Health Before the FDA

This is the least safe time in history for eating, right? Wrong. If you find it terrifying feeding your family now, try imagining yourself in Washington or New York from the 1850s to the 1900s. You try to buy vinegar; you are sold sulfuric acid. Your peas come greened with copper, giving you a dose of heavy metal poisoning with every bite. Spices are bulked with breadcrumbs or sawdust. Children’s candies are colored with poisonous lead. Canned goods are laced with copper, tin and toxic preservatives. You buy “fresh country milk” to feed your baby, only to be sold disgusting swill milk from cows kept in stables attached to distilleries and fed on the alcoholic “mash” left over from making liquor. To disguise its thin bluish appearance, swindlers have thickened it with plaster of Paris and colored it yellow with molasses. There’s a good chance your baby will die from drinking it, as a reported 8,000 infants in New York City did in 1857. Or what about meat? If you think industrial meat production is scary today (and you’re not wrong) you could at least be grateful that you’re not living in the part of Chicago known as Packingtown in the early 1900s. Sausages contaminated with rat dung, spoiled hams disguised with chemicals and “potted chicken” that was really rotten pork were just a few of the scandals exposed by Upton Sinclair in his 1906 novel, “The Jungle.” Source: The Washington Post, by Bee Wilson 

GENETICS

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Diet May Protect Against Gene Changes in Smokers

There has been considerable debate regarding the relationship between diet and cancer prevention. Previous studies, such as the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Trial, showed an increased risk of lung cancer in smokers who took beta-carotene supplements, while other studies have suggested an association between a low folate intake and increased lung cancer risk in current and former smokers. Higher folate intake has also been associated with lower methylation of genes in colorectal tumors as well. While methyl groups are simple four-atom molecules, their addition to DNA can affect whether the gene is expressed, i.e., whether the gene’s signal to produce a protein is actually sent. Many genes involved in critical cell functions, including cell division, are methylated in lung tumors. As seen in previous studies, gene methylation is likely to be a major mechanism in lung cancer development and progression, as well as a potential marker for the early detection of lung cancer. According to an article published online in Cancer Research (12 January 2010), leafy green vegetables, folate, and some multivitamins could serve as protective factors against lung cancer in current and former smokers. The study examined cells that were coughed up by current and former smokers. Upon careful study of the cells and by comparing those cells with profiles of smokers’ dietary intake of leafy green vegetables, folate, and some multivitamins, it was found that those particular substances could influence the prevalence of cellular gene methylation. In the study, slightly more than 1,100 current and former smokers from the Lovelace Smokers Cohort submitted sputum samples and completed questionnaires regarding their dietary intake. Most (75%) of the participants were women who had been enrolled in the study since 2001. Men were not enrolled until 2004. The study analyzed cells in the sputum samples for the methylation status of eight genes that were linked to increased risk for lung cancer in previous studies. Two of the genes, p16 and MGMT, have been found to be highly associated with increased methylation rates. The study next investigated associations between 21 dietary variables and methylation. Both higher intake of leafy green vegetables and higher intake of folate were significantly associated with a reduced probability of high methylation. Current multivitamin users also had less DNA methylation, although there was no association between the duration of multivitamin use and methylation. According to the authors, gene methylation is a promising marker for lung cancer, and understanding the factors underlying methylation is a high priority could be used for early detection and chemoprevention of lung cancer.

Morphine Use after Combat Injury in Iraq and Post-Traumatic Stress Disorder (PTSD)

Target Health is pleased to announce that it has collaborated with one of our clients and the US Army for another indication to assess response to trauma in Iraq and in the US.

Post-traumatic stress disorder (PTSD) is a common adverse mental health outcome among seriously injured civilians and military personnel who are survivors of trauma. According to an article published in the New England Journal of Medicine (2010;362:110-117), pharmacotherapy in the aftermath of serious physical injury or exposure to traumatic events may be effective for the secondary prevention of PTSD. For the study, 696 injured U.S. military personnel were identified without serious traumatic brain injury from the Navy–Marine Corps Combat Trauma Registry Expeditionary Medical Encounter Database. Complete data on medications administered were available for all personnel selected. The diagnosis of PTSD was obtained from the Career History Archival Medical and Personnel System and verified in a review of medical records. Among the 696 patients studied, 243 received a diagnosis of PTSD and 453 did not. The use of morphine during early resuscitation and trauma care was significantly associated with a lower risk of PTSD after injury. Among the patients in whom PTSD developed, 61% received morphine; among those in whom PTSD did not develop, 76% received morphine (odds ratio, 0.47; P<0.001). This association remained significant after adjustment for injury severity, age, mechanism of injury, status with respect to amputation, and selected injury-related clinical factors. The authors concluded that the findings suggest that the use of morphine during trauma care may reduce the risk of subsequent development of PTSD after serious injury.

Use of Angiotensin Receptor Blockers and Risk of Dementia in a Predominantly Male Population

According to an article published in the British Medical Journal (2010;340:b5465) a study was performed to investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases. The study used the administrative database of the US Veteran Affairs, 2002-2006. The population included, 819,491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. The main outcome measures were time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the “cardiovascular comparator”) over a four year period. The statistical analysis included Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia. Results showed that the hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 compared with the cardiovascular comparator and 0.81compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51) and death (0.83). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54) and admission to a nursing home (0.33). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease. According to the authors, angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.

Science & Research at CBER

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

Science & Research at the Center for Biologics Evaluation and Research (CBER)

In order to provide effective regulatory review of biological products, the Center for Biologics Evaluation and Research conducts active mission-related research programs. This research greatly expands our knowledge of fundamental biological processes and provides a strong scientific base for regulatory review. A wide variety of changing technical and scientific issues related to the safety, potency and efficacy of novel biological products requires knowledge of new developments and concepts of basic research in the relevant biological disciplines. Because of the rapid advancement in both conventional and new biotechnologies, the scope of research is both diverse and dynamic. The Web site provides information for the public on various research programs being conducted at the Center, and the many scientific articles published by CBER’s scientists. CBER also offers research related job opportunities in the form of research fellowships and staff positions.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

Target Health (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing. Target Health has developed a full suite of eClinical Trial software including 1) Target e*CRF® (EDC plus randomization and batch edit checks), 2) Target e*CTMS™, 3) Target Document®, 4) Target Encoder®, 5) Target Newsletter®, 6) Target e*CTR™ (electronic medical record for clinical trials). Target Health ‘s Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.