While nanotechnology is being used in everything from paints to car exteriors, clothing and cosmetics, research is also underway using the technology to discover medical breakthroughs. Nanoparticle research by Professor Sanku Mallik and his group at North Dakota State University, Fargo, appears in the July issue of the Review of Ophthalmology in the article “Nanoparticles: Into the New Frontier.” http://www.revophth.com/index.asp?page=1_13901.htm

The article by senior editor Christopher Kent notes that cutting-edge work is being done in North Dakota, Oklahoma and Florida. The promise of such research includes finding treatments for eye diseases such as glaucoma and macular degeneration. Sanku Mallik, associate professor of pharmaceutical sciences at NDSU, conducts research that uses a nanoparticle called nanoceria as a drug delivery device. It is made of cerium oxide molecules. The brain-blood barrier can prevent medicines from reaching their therapeutic targets, but nanoparticles are so small they are capable of crossing the brain-blood barrier. Quoted in the article, Mallik notes, “So far, nanoceria appears to be nontoxic, but the drugs we attach to the particle might be toxic, so targeting molecules are necessary. These particles can also be used for imaging; we can attach molecules that can be made to glow after they reach targets such as cancer cells.”

So far, the research of Mallik and his associates has been conducted in a controlled environment outside of a living organism and is in its initial stages. Researchers must ensure that the particles are water-soluble for effective delivery and less irritation to the cornea. Glaucoma is the leading cause of blindness if left untreated, according to the Glaucoma Research Foundation. An estimated four million Americans have glaucoma but only half of them know it, according to Prevent Blindness America. Minnesota Twins center fielder Kirby Puckett (1960-2006) was forced to retire due to loss of vision in one eye from glaucoma. Age-related macular degeneration is the leading cause of visual impairment and blindness in Americans older than 50, affecting more than two million people, according to the American Academy of Opththalmology.

The pharmaceutical research of Mallik’s team includes attaching anti-cancer drugs to the nanoparticles and targeting molecules so particles only enter cells that are in need of treatment. Nanotechnology is often defined as the science of the extremely small. A nanometer, for example, is a hundred-thousandth of the thickness of a human hair, or one-billionth of a meter.

Mallik recently received a five-year, $1.46 million grant from the National Institutes of Health National Cancer Institute. D. K. Srivastava, professor of biochemistry and molecular biology at NDSU, is the co-investigator on this award. It relies on the complementary scientific expertise of Mallik and Srivastava. The grant will allow the investigators to prepare selective, “multi-prong” inhibitors for matrix metalloproteinases using lipid-based nanoparticles. They also will use the nanoparticles for isozyme-selective detection of these enzymes.

Mallik received his bachelor’s degree in chemistry from the Indian Institute of Technology, Kharagpur, India, and his doctorate degree in organic chemistry at Case Western Reserve University, Cleveland, Ohio. He completed post-doctoral work at the California Institute of Technology, Pasadena, Calif. He is a past recipient of a National Science Foundation CAREER award, which recognizes and supports the early career-development activities of scholars who are likely to become the academic leaders of the 21st century. Information about Dr. Mallik’s research is available at http://pharmsci.ndsu.nodak.edu/facstaff/mallik/research.htm

A University of California, San Diego School of Medicine researcher has developed the first tissue culture of normal, human liver cells that can model infection with the Hepatitis C virus (HCV) and provide a realistic environment to evaluate possible treatments. The novel cell line, described in the July 16 issue of PLoS ONE will allow pharmaceutical companies to effectively test new drug candidates or possible vaccines for the HCV infection, which afflicts about 170 million people worldwide. Currently, there is no animal model that is effective for testing such therapies.

Assistant Professor of Medicine Martina Buck, Ph.D., researcher at UC San Diego’s Department of Medicine and Moores UCSD Cancer Center developed the novel culture system, which mimics the biology of HCV infection in humans.

“This is the first efficient and consistent model system for HCV to be developed,” said Buck, adding that it will now enable researchers not only to conduct mechanistic experiments in culture, such as blocking the virus pathways, but also to more effectively screen possible therapies for HCV. “There is a need for new treatments, and for development of a possible vaccine for HCV. Now we have a model system to support work by investigators in this area.”

Currently, there is only a single treatment for HCV, PEG- interferon-?. The drug combination has an average response rate of about 50 percent in HCV cases, but it is much lower than that, closer to 20 percent, in individuals with liver cirrhosis. It can also cause severe flu-like side effects. Approximately 10,000 deaths due to cirrhosis of the liver and several thousand more from liver cancer are attributed to HCV infection in the United States each year.

The HCV life cycle is only partially understood because, until now, it has not been possible to efficiently infect normal human hepatocytes, or liver cells, in culture. According to Buck, the valuable Huh-7 system currently in use to test HCV uses cloned, synthetic HCV RNA expressed from liver tumor cells. These cells cannot be infected with naturally occurring HCV obtained from infected patients.

In contrast, the culture developed by the UCSD scientists allows direct infection with HCV genotypes 1, 2, 3 and 4 from the blood of HCV-infected patients. This system will enable researchers to study the complete viral lifecycle in its normal host cell, providing novel scientific opportunities. The study reports that the system has been tested using over 30 virus donors as well as multiple donors of hepatocytes, with the production of infectious HCV for all genotypes tested.

This work was supported by grants from the National Institutes of Health, the Department of Veterans Affairs (Merit Review) and the Medical Research Foundation at UC San Diego. Buck is a recipient of the Howard Temin Award from the National Cancer Institute.

Tobacco addiction starts early, and public health experts agree that it is important to keep tobacco out of the hands of adolescents. Still, what works for prevention is a matter of controversy, and a new systematic review suggests that there is no clear answer.

Review authors Lindsay Stead and Tim Lancaster at the University of Oxford examined 35 studies to determine whether programs targeting shopkeepers who sold tobacco to minors actually reduced how much teens smoked.

Simply informing merchants about the law had no effect on reducing sales to minors, the review found. Rather, the most successful initiatives used a variety of tactics, including retailer education, personal visits from law enforcement personnel, and posters and public information campaigns to increase community awareness.

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

The 35 included studies examined a variety of interventions focused on retailers including educating them about the law, checking up on them via sting operations, notifying them of compliance check results and punishing violators with fines or license suspensions. Studies also looked at community-based strategies, such as public information campaigns.

Researchers measured how well strategies worked by (1) a reduction in illegal sales, which was assessed by test purchasing; (2) changes in young people’s smoking behavior; and (3) surveys of teens to find out whether they thought it was easier or harder to procure forbidden smokes.

Getting access to cigarettes has gotten harder, but it is still relatively easy, according to the review: In 1996, 91 percent of kids surveyed said it was at least “fairly easy” to procure tobacco; a 2007 survey found that number had dropped to 78 percent.

The theory is that if kids cannot buy cigarettes or other tobacco products at stores, they will smoke less. The problem with focusing on retailers is that kids can also get tobacco in other ways: from their parents, siblings or friends — or even by stealing. Therefore, spending money on enforcement of laws against selling to minors might not be cost-effective.

“You can clearly reduce the number of shopkeepers who make illegal sales by test purchaser or sting, but there are many reasons to think that’s not a good way to measure real-life behavior,” Stead said.

David Pearson, associate director of the Center for Community Health and Evaluation, said the review demonstrates how difficult it is to perform evaluations in community settings. “Rigorous, controlled trials are complex, expensive and subject to all the other influences in the communities,” said Pearson, who had no affiliation with the review.

Community support appears to be crucial for several reasons. For one, if adults do not think adolescent smoking is a problem, some are willing to buy cigarettes for the kids. For another, one study found that judges tended to suspend sentences on clerks, because they felt the penalties were too harsh. It is also important that laws and penalties are somewhat standardized across the region; otherwise, merchants might resent the loss of tobacco revenue to their competitors a few miles down the road.

None of the controlled studies reviewed provided conclusive evidence that making it harder to buy cigarettes actually reduced underage smoking. The biggest problem, the authors found, was that intervening with retailers never put a complete stop to illegal sales.

Pearson said that cigarettes bummed from adults or peers is a major source of the contraband: “Even if access through retail outlets is effectively restricted, as we’ve been able to do in King County, Washington, an equally important issue is changing the culture that thinks it is OK for kids to get cigarettes from social sources.”

Intervening with retailers could be an effective part of a comprehensive tobacco control strategy, but it does not seem to be the whole answer, the review found. “Put your money into community-wide efforts as well, instead of focusing on preventing the selling of tobacco to minors,” Stead said. “If you can change community norms and reduce smoking among adults — that will ultimately be more useful.”

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

Stead LF, Lancaster T. Interventions for preventing tobacco sales to minors (Review). Cochrane Database of Systematic Reviews 2008, Issue 3.