In a finding that’s making national headlines, researchers at Case Western Reserve University have detected tiny amounts of Iodine 131 from Japan in rainwater collected from the roof of the A.W. Smith Building.

Gerald Matisoff, professor of geology, said the presence of the isotope presents no danger to human health. He estimated the level of radiation is about one-tenth that of natural background radiation.

“In theory, the Iodine 131 could have come from any radioactive waste processing facility,” Matisoff said. “But, we know it’s from Japan. The isotope is being seen worldwide.”

Matisoff and graduate student Mary Carson collect water on the roof of the A.W. Smith Building, on the campus quad, to monitor the particulates being carried in rain into Lake Erie.

Carson first detected the iodine 131 in a sample she analyzed Friday. Matisoff confirmed the finding yesterday.

New research from a Case Western Reserve University School of Medicine professor shows that medications that have raised safety concerns over heart attack and stroke risks might not have gotten approval from the Food and Drug Administration (FDA) if the cardiovascular effects of fluid retention had been better understood. Robert P. Blankfield, clinical professor of family medicine and a member of the Department of Family Medicine at University Hospitals Case Medical Center, said fluid retention may explain the increased risk of heart attacks and strokes of medications such as Vioxx, Bextra and Avandia.

His research, published in Clinical Hemorheology and Microcirculation (IOS Press, ISSN 1386-0291), calculates the effects of fluid retention upon the velocity of blood flow and the turbulence of flowing blood. These calculations demonstrate that fluid retention increases the risk of heart attacks and strokes. Since numerous medications cause fluid retention, the paper’s findings have implications to ensure drugs on the market are safe. The pain medications Vioxx and Bextra and the anti-diabetic medication Avandia cause fluid retention. Vioxx and Bextra, known as cyclo-oxygenase-2 (COX-2) inhibitors, were withdrawn from the market because of safety concerns over heart attacks and strokes, and Avandia has been suspected in some reports of increasing the risk of heart attacks.

Blankfield used several basic cardiovascular and hydraulic equations to demonstrate that fluid retention is detrimental for the cardiovascular system. 

Fluid retention increases the likelihood that blood will flow in a turbulent manner. Turbulent blood flow accelerates atherosclerosis (hardening of the arteries), thereby increasing the risk of heart attacks and strokes. Many medications cause fluid retention, which raises blood pressure in some, but not all, individuals. Physicians worry about fluid retention if it does raise blood pressure, but are unconcerned when blood pressure is unaffected.

“This paper demonstrates that fluid retention is unhealthy because it increases the likelihood that blood will flow in a turbulent manner regardless of whether or not blood pressure is raised. Therefore, drugs that cause the body to retain fluid are dangerous for the cardiovascular system,” Blankfield said. 

“If the FDA had been aware of the increased cardiovascular risk that arises from drugs that cause fluid retention, Vioxx, Bextra and Avandia might never have been approved. These findings might spur the FDA to alter some of its current policies,” he continued. “The calculations in this paper might also help pharmaceutical manufacturers screen drugs for their cardiovascular risk at an early stage in the drug development process.” For more information, click here.

Researchers at Case Western Reserve University have developed a little bomb that promises a big bang for cancer patients.

Preliminary tests show an anti-cancer drug loosely attached to gold nanoparticles starts accumulating deep inside tumors within minutes of injection and can be activated for an effective treatment within two hours. The same drug injected alone takes two days to gather and attacks the tumor from the surface—a far less effective route.

Speeding anti-cancer drugs directly into tumors enables patients to receive lower doses of the toxic chemicals, thereby saving healthy tissue from damage and other harsh side effects suffered in traditional chemotherapy.

“We hope to lower the dosage by at least a factor of 10,” said Clemens Burda, associate professor of chemistry and senior author of the paper. The research team comprised Burda, graduate students Yu Cheng and Joseph D. Meyers, research assistant professor of biomedical engineering Ann-Marie Broome, chemistry professor Malcolm E. Kenney and associate professor of biomedical engineering James Basilion.

The key to success? The scientists tied an anti-cancer drug to golden missiles using a weak chemical interaction called a noncovalent bond. In molecule construction, a covalent bond is a heavy rope lashed and knotted; a noncovalent bond is a shoestring tied in a bow.

“Very often, additions to chemical systems change properties of the components of the system,” Burda said. Attempts by his and other research groups to use covalent bonds for drug delivery have resulted in such complications and less than hoped-for results.

The researchers, who come from a breadth of disciplines, found that by using a noncovalent bond to attach the drug to coated gold, they eliminated interference among the desired properties of each component.

Burda’s group sought to simplify the process by using materials that have well-known properties.

The work, titled “Deep Penetration of a PDT Drug into Tumors by Noncovalent Drug-Gold Nanoparticle Conjugates,” was published in February in the online edition of the Journal of the American Chemical Society. To read more, click here.

Astronomy professor Heather Morrison and Case Western Reserve Observatory Manager Paul Harding have each been named to “Architect Status” in the newest phase of the Sloan Digital Sky Survey.

Hundreds of scientists in more than 20 countries worldwide are involved in the effort to map the distribution of stars and galaxies in our universe.

The Case Western Reserve University researchers were singled out for extraordinary contributions, a reflection not only of their expertise and capabilities but also their professional leadership and development, said Chris Mihos, chair of the astronomy department.

Morrison, professor of astronomy, received the honor for her work on the Sloan Extension for Galactic Understanding and Exploration. The program investigates the Milky Way’s structure, formation history; paths of movement, speed and chemical makeup of stars; and more for clues explaining the formation and evolution of galaxies.

Harding, Observatory Manager, earned the award based on his scientific and technical contributions to the ongoing third phase of the digital sky survey. He helped develop instrumentation critical to mapping the structure and dynamics of the Milky Way, find and characterize extrasolar planetary systems, and understand dark energy and the nature of the universe.

The SDSS project is a major international project surveying the sky and mapping out the distribution of stars and galaxies in our universe. It is one of the most influential projects in modern astronomy, and has revolutionized many areas of astronomy and cosmology. More than 400 scientists are involved the SDSS-III project at more than 20 institutions spanning the globe.

Magnetic technology could help address a major problem that bioengineers face as they try to create new tissue: getting human cells to not only form structures, but to stimulate the growth of blood vessels to nourish their growth.

A team of investigators from Case Western Reserve University, Duke University and University of Massachusetts, Amherst, created an environment where magnetic particles suspended within a special liquid solution acted like molecular sheep dogs, nudging free-floating human cells to form chains in response to external magnetic fields. These chains, the researchers said, could potentially be integrated into approaches for creating human tissues and organs.

These cells not only naturally adhere to each other upon contact, the researchers said, but the aligned cellular configurations that form may promote or accelerate the creation and growth of tiny blood vessels.

“The cells have receptors on their surfaces that have an affinity for other cells,†said Melissa Krebs, a third-year biomedical engineering graduate student at Case Western Reserve University. “They become sticky and attach to each other. When endothelial cells get together in a linear fashion, as they did in our experiments, it may help them to organize into tiny tubules.â€

The iron-containing nanoparticles used by the researchers are suspended within a liquid known as a ferrofluid. One of the unique properties of these ferrofluids is that they become highly magnetized in the presence of external magnetism, which allows researchers to readily manipulate the chain formation by altering the strength of the magnetic field.

At the end of the process, the nanoparticles are simply washed away, leaving a linear chain of cells. That the cells remain alive, healthy, and relatively unaltered without any harmful effects from the process is one of the major advances of the new approach over other strategies using magnetism.

“Others have tried using magnetic particles either within or on the surface of the cells,†explained Randall Erb, a fourth-year graduate student in the laboratory of Benjamin Yellen, assistant professor of Mechanical Engineering and Materials Science, at Duke University’s Pratt School of Engineering and Krebs’ brother. “However, the iron in the nanoparticles can be toxic to cells. Also, the process of removing the nanoparticles afterward can be harmful to the cells and their function.â€

The key ingredient for these studies was the synthesis of non-toxic ferrofluids. Researchers developed a method for coating the magnetic nanoparticles with bovine serum albumin (BSA), a protein derived from cow blood. BSA is a stable protein used in many experiments because it is biochemically inert. In these experiments, the BSA shielded the cells from the toxic iron.

“The other main benefit of our approach is that we are creating three-dimensional cell chains without any sophisticated techniques or equipment,†Krebs said. “Any type of tissue we’d ultimately want to engineer will have to be three-dimensional.â€

For their experiments, the researchers used human umbilical vein endothelial cells. Others types of cells have also been used, and it appears to the researchers that this new approach can work with any type of cell.

“While still in the early stages, we have shown that we can form oriented cellular structures,†said Eben Alsberg, assistant professor of Biomedical Engineering and Orthopaedic Surgery at Case Western Reserve. “The next step is to see if the spatial arrangement of these cells in three dimensions will promote vascular formation. A major current hurdle in tissue engineering is vascularization, and we hope that this technology may help to address the problem.â€

The research, appearing online in advance of the May publication of Nanoletters, a journal published by the American Chemical Society, was supported by the National Institutes of Health, the National Science Foundation and Case Western Reserve University.

Leaded gasoline was responsible for about two-thirds of toxic lead that African-American children in Cleveland ingested or inhaled during the latter two-thirds of the 20th century, according to a new study in Science of the Total Environment.

Researchers from Case Western Reserve University say what they've shown in Cleveland probably applies to many cities across the U.S. and reinforces concerns about the health threat for children in countries still using leaded gasoline. However, they emphasize that the results do not minimize the ongoing importance of current childhood lead exposure due to persistence and deterioration of leaded paint which was used as late as the 1960's.

Extrapolation from lead analyses of teeth from 124 residents of urban Cleveland neighborhoods show that “at the peak of leaded gasoline usage, in the 1960's and early 70's, the levels of lead in the bloodstream were likely to be toxic,†said Norman Robbins, emeritus professor of neurosciences at Case Western Reserve School of Medicine. Research of others has shown that these levels of lead are associated with significant neurological and behavioral defects lasting into adulthood, he said.

"It raises the question, has leaded gasoline had a lasting effect on many present-day Cleveland adults?" Robbins said.

Robbins, who began the study 17 years ago, put together an interdisciplinary team to determine what was the predominant recent historic source of lead exposure within the city. Leaded gasoline, lead paint, and lead soldering in food cans had been implicated.

"The findings are important today," said Jiayang Sun, professor of statistics at CWRU and a co-author of the study. "Some countries are still using leaded gasoline."

The United Nations Environment Programme says Afghanistan, Myanmar and North Korea rely on leaded gasoline while Algeria, Bosnia, Egypt, Iraq, Serbia and Yemen sell both leaded and unleaded gasoline.

The researchers here used a comprehensive analysis of data collected from multiple sources, including the Cleveland tooth enamel data from 1936 to 1993, two different Lake Erie sediment data sets (one collected by faculty from the CWRU Geology dept), data from the Bureau of Mines and traffic data from the Ohio Bureau of Motor Vehicles.

Because blood tests to determine lead levels were unreliable prior to the mid 1970s, the team used lead levels in the enamel of teeth removed from adults at Cleveland dental clinics to determine their childhood lead exposure.

James A. Lalumandier, chairman of the Department of Community Dentistry at CWRU's School of Dental Medicine, obtained teeth, which were removed from for dental reasons. Richard A. Shulze, a former dental student now in private practice, developed the method to extract lead samples from the enamel.

They trimmed the outer layers to reveal lead trapped within the enamel of developing first and second molars. Like trees, teeth grow in layers around the center, Lalumandier said. The enamel layers in first and second molars provide a permanent record of the lead to which the tooth’s owner was exposed, with mid-points of lead incorporation at about ages 3 and 7, respectively. The researchers obtained the birthplace, age, sex and race of the owners and wound back the clock.

Chemistry Professor Michael E. Ketterer began the lead analysis at John Carroll University in Cleveland and continued after moving to Northern Arizona University.

Lead levels in the teeth were compared to reliable blood levels taken in the 1980s and 1990s, Lake Erie sediment cores that reflect atmospheric lead levels of the past, as well as leaded gasoline use by year.

Sun and former PhD student Zhong-Fa Zhang, now at the Wistar Institute in Philadelphia, who joined in the study in late 2003, developed and applied modern statistical methods to mine the information and compare data curves created with the tooth, blood, sediment and usage data. The impact of the new statistical technique motivated by this study, goes beyond this lead application; it has a general application to simultaneous comparison of curves needed in other biomedical data applications.

The data shows leaded gasoline was the primary cause of exposure, with lead levels in teeth comparatively low in 1936 and increasing dramatically, mirroring the usage of leaded gas and atmospheric lead levels, which tripled from the 1930s to the mid 1960's.

The time dependency of the lead isotope ratios in tooth enamel, measured in Ketterer's laboratory, also closely matched that of atmospheric deposition from gasoline. If the main source of lead in teeth had been lead from paint and food can solder that were commonly used at the turn of the last century up through the 1960s, the data would have shown consistently high levels of lead in teeth already in the 1930s and a modest rise as lead was introduced into gasoline from that decade up until usage peaked in the mid 1960s.

Traffic data kept by the Ohio Department of Transportation reinforced the finding. The researchers found that children in neighborhood clusters with the highest number of cars on their roads also had the highest levels of lead in their teeth.

Cleveland is hardly unique in the nation's history of lead usage and exposure, Robbins said. "What we found here we expect to be similar to urban areas in the rest of the country."

The study was funded by the Mary Ann Swetland Endowment, Case Western Reserve University and by grants or programs of the National Science Foundation.

The famous hominid fossil Lucy has family. An announcement yesterday in the early online edition of the Proceedings of the National Academy of Science (PNAS) says the relative—although 400,000 years older—was, like Lucy, an advanced upright walker.

Three Case Western Reserve University researchers: Yohannes Haile-Selassie, Bruce Latimer and Beverly Saylor, were among an international team of scientists who reported the most complete skeleton so far of a 3.6 million-year-old Lucy species, Australopithecus afarensis.

Other researchers were from the Cleveland Museum of Natural History, Kent State University, Addis Ababa University and Berkeley Geochronology Center, and researchers from Sweden and France. Latimer, interim director of the CWRU Center for Human Origins—a component center of the Institute for the Science of Origins—and an adjunct professor of anatomy at the School of Medicine, co-directed the Woranso-Mille Paleontological Project with Haile-Selassie, the lead investigator of the study reported in PNAS.

The finding is nicknamed "Kadanuumuu," which means big man, because of his height, determined to range from 5 feet to 5 feet 6 inches tall. In comparison, Lucy, found in 1974, was determined to be a small female about 40 inches tall. Kadanuumuu provides a glimpse into the evolution of man, generating new information about locomotion, shoulder morphology and the rib cage. According to the researchers, nearly 1 million years before stone tools were made, Kadanuumuu already had long legs like the modern human. This overturns the theory that man developed long legs to walk miles during persistent hunting.

The bones were among 4,500 fossil mammalian specimens found. Some 95 fossil hominid specimens, as old as 3.8 million years, are among those discovered.

"As a result of this discovery, we now know Lucy and her relatives better than ever," said Haile-Selassie, the curator and head of physical anthropology at the Cleveland Museum of Natural History and a fellow of the Center for Human Origins.

"Partial skeletons are rare, which is why they are so valuable," Latimer said. "This particular skeleton preserves portions of the shoulder and thoracic cage—elements not previously found together in an associated individual."

He added that Kadanuumuu's shoulder complex was more like humans' and not at all like chimpanzees', which are knuckle-walkers.

"The idea that humans went through a knuckle-walking phase can now be discarded," Latimer said.

Collaborating as the project's geologist and dating the soils surrounding the fossil skeleton was Saylor, associate professor of geological sciences in the College of Arts and Sciences.

Through early indicators in the soil around the fossil remains, Saylor estimates the hominid's age at approximately 3.6 million years, making it the oldest specimen in the group of Australopithecus afarensis.

The species was named after the Afar region of Ethiopia. Lucy was found in the Hadar in the Afar region.

Studies have indicated that insects rely on their brains to respond to what they feel and see. But for the first time, researchers have shown a direct link between neurons at the center of an insect brain and changes in behavior. The findings and a video are published online in Current Biology. A team led by Roy Ritzmann, Case Western Reserve University biology professor, recorded neural activity in the central complex of walking cockroaches—that in itself is a painstaking first. They found that in the same area of the brain where visual, chemical and tactile information from the world outside is processed, the firing of neurons is correlated to the insect's stepping rate. That is, cockroaches walk or run when their brains decide to do so. So what? Well, what if robots could do as much? "Robots were sent into the World Trade Center after 911," Ritzmann said. "By the time the driver would see an obstacle, they were stuck." "We see in these animals an ability to adapt to difficult and changing terrain and conditions," he continued. "What we'd like to see is a robotic brain that can make these kinds of decisions." He believes the research could help lead to better robots to search collapsed mines and buildings, to pilot drones, and for space exploration, where signals from Earth to a far off planet takes minutes, hours or longer. So, to make a robot that can turn, back up, climb over or burrow under and obstacle without the guidance of a far off rescue worker using computer controls, what could be better than mimicking an insect's comparatively simple brain? Easier said than done. To get these first recordings of neural activity, Research Assistant Allan Pollack spent more than a year perfecting techniques to perform brain surgery in an area the size of the head of a pin. After delicately cutting through the brain sheath and exposing the central complex, he inserted a hair-thin braid of four wires that can monitor activity of groups of neurons or stimulate the groups with electricity. With the braid implanted, cockroaches were tethered over the simplest version of a treadmill: a greased glass plate. The researchers waited, sometimes for three hours or more, for a cockroach to begin walking, and to change speeds, all without prodding. "We wanted to study the cockroach when it wants to move," Ritzmann said. The researchers filmed the insects walking in place while recording groups of neurons firing. Watch a clip. John Bender, a postdoctoral research associate, crunched the raw data. He found that when he graphed the sums of the insects' step rates and sums of the neural firing, they produce a similar pattern. The steps come about 450 milliseconds after the neural firing. To test whether neural activity is more than coincidental to stepping, the researchers used electrical stimulation to make the neurons fire. In some, the step followed about 450 milliseconds later. "This is a breakthrough on a number of different levels," said Sasha Zill, a professor of anatomy and pathology at the Joan C. Edwards School of Medicine at Marshal University. Zill, who studies how the nervous system generates movement, and is familiar with this research, said, "It was a real accomplishment to record the neural activity of walking. The interesting finding is the cockroach can control speed with the brain." Zill explained research shows animals from humans to—now, cockroaches—walk by sending a signal from the brain down to a part of the spinal cord or the equivalent, which generates a pattern of signals that direct the orderly contraction of muscles needed for each step. To take a closer look at what's occurring in the cockroach brain to initiate and speed stepping, Ritzmann, Pollack and Bender plan next to record changes within individual neural cells.