02.20.08

Pathogens & Parasites

Posted in Biology at the University of Virginia, Infectious Disease, Jacob Canon, Parasites, The Oscar Show, UVa College of Arts & Sciences, Uncategorized, University of Virginia, biology, biomedical engineering, immune, physical health at 12:10 pm by Jacob Canon

In today’s show, adapted from an article published this month on the Oscar Web site written by Mary Jane Gore, we look at the research of Dr. William Petri, chief of the UVa Division of Infectious Diseases and International Health, and his study of a voracious parasite that is said to kill nearly 100, 000 people each year.

If you have ever contemplated working as a biological researcher then you would probably have considered these questions: what happens when a cell’s life ends? And, what are the mechanisms that control decay?

Contemplating just these types questions during a recent study, a UVa-led research team, directed by Dr. William Petri, chief of the UVa Division of Infectious Diseases and International Health, made discoveries which are helping to stop one of the world’s most voracious parasites.

The team included Douglas Boettner (now completing postdoctoral work in Miami), U.Va. graduate students Alicia S. Linford and Sarah Buss and faculty colleagues Dr. Eric Houpt and Dr. Nicholas Sherman of UVa and Dr. Christopher D. Huston of the University of Vermont.

Their work revolved around the hypothesis that identifying molecules involved in the corpse ingestion would provide insight into how the amoebae cause colitis in children. These amoebae, properly known as entamoeba histolytica, cause colitis, or inflammation of the colon. They do this by attacking and killing human immune cells in mere seconds. It then it hides the evidence by eating the cells’ corpses.

In doing so, per data from Dr. Gerald Mandell of U.Va. Infectious Diseases and editor of Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases, 6th edition, this murderous marauder “on a global basis, affects approximately 50 million people each year, causing diarrhea, malnutrition and nearly 100,000 deaths.

Dr. Petri’s team identified a particular protein on the surface of the ameba called a kinase, PATMK. Their work, published in the Jan. 18 issue of PLoS Pathogens, a peer-reviewed, open-access journal from the Public Library of Science, outlined a special technique called RNA interference, which inhibits the actions of this kinase, thus preventing the amoebae from eating the dead cells.

Dr. Petri, said, “by blocking this kinase, we have for the first time prevented the ameba from colonizing and invading the gut. This means that we are a step closer to preventing this disease, which wreaks havoc among children worldwide.”

The first author of the paper, Douglas Boettner said, “infection and further invasion into the gut require the clearance of dead cells in order to prevent immune recognition of the damaged tissue. PATMK is the first individual member of a large family of proteins to be assigned a function related to the clearance of dying tissue during pathogenesis.”

Boettner added, “this protein may be a pivotal vaccination target because these preliminary studies show that alterations in PATMK function reduced progression of amoebiasis in mice, a vaccine that ultimately would prevent this ameba from clearing the damaged host may draw in helpful immune cells, and thus help to clear this infection.”

Their work has shown how infection depends upon the ameba’s consumption of dead cells. By identifying the molecule that controls this consumption, scientists are one step closer to the ultimate goal of preventing the diseases caused by this parasite.

You’ve been listening to the Oscar Show, I’m Jacob Canon. Join us next week when our topic will be the research of Adrienne Felt, a fourth-year computer science major in the School of Engineering and Applied Science, concerning privacy issues surrounding social networking platforms such as Facebook.

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01.23.08

The HemoShear 2.0

Posted in Atherosclerosis, Cardiology, Jacob Canon, MRI, Skalak, The Oscar Show, UVa College of Arts & Sciences, Uncategorized, University of Virginia, biomedical engineering, pharmaceutical, physical health at 12:12 pm by Jacob Canon

A new device invented by researchers at the University of Virginia could save pharmaceutical companies significant time and money in screening potential new drug compounds. Brett Blackman, an assistant professor in biomedical engineering and Brian Wamhoff, assistant professor in the department of medicine; cardiovascular division, teamed up to create a novel system, the HemoShear 2.0, which, for the first time, offers researchers the ability to observe the behavior patterns of human vascular cells under a variety of blood flow conditions that occur inside the body’s cardiovascular system.

Dr. Blackman said, “We want to help the pharmaceutical industry identify effective therapeutic compounds by allowing them to fail early, fail fast and fail cheap before going to very expensive animal studies.”

Atherosclerosis, hardening or narrowing of the arteries, is considered the most important underlying cause of heart attack or stroke. The HemoShear 2.0 models the early indicators of atherosclerosis by placing actual human endothelial cells, the cells lining the interior of blood vessels, and smooth muscle cells, the cells found in the wall of blood vessels, in an environment that mimics an artery with blood flowing through it. Data from these exposures are recorded and measured to help test the efficacy of therapeutic compounds and aid in early stage toxicity studies. Instead of testing drug compounds on isolated cells, which can produce false negatives, drug companies can use the device to test compounds in a more realistic environment.

This kind of modeling offers unique opportunities to observe the cells and their interaction. This interaction is important because the cells lining the interior of the blood vessels recognize different blood flow patterns imposed upon them and respond by expressing or repressing genes. This, in turn, influences their interactions with the cells found in the walls of blood vessels. The researchers found these cell interactions may lead to the onset of early-inflammation-associated atherosclerosis in certain arteries.

MRI’s were used by researchers to determine the rhythmic pattern that blood flows through different arteries in human subjects. Blackman said, “We are then able to simulate the same flow patterns in those areas that are more or less susceptible to atherosclerosis and observe how the cells respond to these flow patterns in HemoShear.”

Using a synthetic elastic layer that is similar to a real blood vessel wall, endothelial cells are plated on the top surface and smooth muscle cells on the bottom surface. Then, the different blood flow patterns modeled from human circulation are applied to the endothelial cells through rotation of a motor-driven cone system. The findings: the blood flow can influence both endothelial and smooth muscle cell behaviors.

When subjected to atheroprotective blood flow patterns, the endothelial cells aligned with the direction of the blood flow, and the smooth muscle cells aligned perpendicularly to the flow as is true in a healthy blood vessel. In stark contrast, the atheroprone type of flow caused the endothelial cells to move away from their parallel structure while smooth muscle cells moved away from their perpendicular structure.

This remodeling mimics the early phases of the diseased state of the artery; the blood flow pattern associated with atheroprone areas resulted in inflammation in both cells reminiscent of early hallmarks of atherosclerosis. This was confirmed through evaluating gene and protein expression profiles in both cell types.

Thomas Skalak, professor and chair of the U.Va. Department of Biomedical Engineering said, “the results of this study validate the use of this novel co-culture system as a relevant biomimetic vascular model for studying early atherosclerotic events. The cells’ responses to these carefully controlled models of blood flow can now be used to develop therapeutic interventions for detection and treatment of vascular diseases. It has the potential to be revolutionary.”

You’ve been listening to the Oscar Show, I’m Jacob Canon. Join us next week as we again delve into the election season, when our topic will be the work of Bryan Pfaffenberger, associate professor at the University of Virginia’s School of Engineering and Applied Science and his study of mechanical-lever voting machines, their history and understanding the interaction between technology and culture that has been going on for more than a century…

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01.19.08

Magnetic Therapy

Posted in Magnetic therapy, Skalak, The Oscar Show, UVa College of Arts & Sciences, Uncategorized, University of Virginia, biomedical engineering, physical health at 3:45 pm by Jacob Canon

In today’s show, adapted from an article published this month on the Oscar web site written by Melissa Maki, we examine the continuing studies of UVa professor and chair of biomedical engineering Thomas Skalak and his efforts to develop real scientific evidence about the effectiveness of magnetic therapy.

Magnetic therapy, touted for healing properties since ancient Greece, is still widely used today as an alternative method for treating a number of conditions, from arthritis to depression. Yet, in spite of no scientific proof that magnets can heal, a lack of regulation and widespread public acceptance based on anecdotal evidence, hopeful consumers have created a $5 billion world market as they buy bracelets, knee braces, shoe inserts, mattresses and other products embedded with magnets, hoping for a non-invasive and drug-free cure to what ails them.

Thomas Skalak, professor and chair of biomedical engineering at U.Va., has carefully studied magnets for a number of years in order to develop real scientific evidence about the effectiveness of magnetic therapy. His lab leads the field in the area of micro-circulation research - the study of blood flow through the body’s tiniest blood vessels. With a five-year, $875,000 grant from the National Institutes of Health’s National Center for Complementary and Alternative Medicine, Skalak and Cassandra Morris, former Ph.D. student in biomedical engineering, set out to investigate the effect of magnetic therapy on micro-circulation.

Initially, they sought to examine a major claim, that magnets increase blood flow, made by the companies that sell magnet. They first found evidence to support this claim in their initial research with laboratory rats. Magnets of 70 milliTesla (mT) field strength - about 10 times the strength commonly found on a refrigerator - were placed near the rat’s blood vessels. Measurements of blood vessel diameter were taken both before and after exposure to the force created by the magnets. They effect found was significant. The vessels that had been dilated constricted, and the constricted vessels dilated, implying that the magnetic field could induce vessel relaxation in tissues with constrained blood supply, ultimately increasing blood flow.

Since dilation of blood vessels is often a major cause of swelling at sites of trauma to soft tissues such as muscles or ligaments, the prior results on vessel constriction led Morris and Skalak to look closer at whether magnets, by limiting blood flow in such cases, would also reduce swelling. Their most recent research, published in the November 2007 issue of the American Journal of Physiology, yielded affirmative results.

In this study, the hind paws of anesthetized rats were treated with inflammatory agents in order to simulate tissue injury. Magnetic therapy was then applied to the paws. The research results indicate that magnets can significantly reduce swelling if applied immediately after tissue trauma.

Since muscle bruising and joint sprains are the most common injuries worldwide, this discovery has significant implications. Skalak said, “if an injury doesn’t swell, it will heal faster - and the person will experience less pain and better mobility.” This means that magnets could be used much the way ice packs and compression are now used for everyday sprains, bumps and bruises, but with more beneficial results.

A key to the success of magnetic therapy for tissue swelling is careful engineering of the proper field strength at the tissue location, a challenge in which most currently available commercial magnet systems fall short. The new research should allow Skalak’s biomedical engineering group to design field strengths that provide real benefit for specific injuries and parts of the body.

The ready availability and low cost of this treatment could produce huge gains in worker productivity and quality of life. Skalak, who plans to continue testing magnet effectiveness through clinical trials and on elite athletes, envisions the magnets being particularly useful to high school, college and professional sports teams, as well as school nurses and retirement communities.

Skalak said, “we now hope to implement a series of steps, including private investment partners and eventually a major corporate partner, to realize these very widespread applications that will make a positive difference for human health.”

You’ve been listening to the Oscar Show… I’m Jacob Canon. Join us next week when continue with the topic of biomedical engineering by examining the work of two University of Virginia professors who have created a system, the HemoShear 2.0, which offers researchers the ability to observe the behavior patterns of vascular cells under a variety of blood flow conditions.

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