Shock treatment: These images show blood flow in the left ventricle of a 62-year-old patient’s heart (red indicates blood flow). The images on the left show the ventricle before acoustic shockwave treatment; the ones on the right show it after treatment.   Credit: R. Erbel, Essen University, Germany

 

A device sends shockwaves to prompt blood vessel growth

 

MIT Technology Review, May 2010, by Lauren Gravitz  –  Cardiac patients are living longer and longer–up to 20 years after receiving stents, a heart bypass, or heart-valve replacements. But extended lifespan is often accompanied by other complications, as a repaired heart can still have difficulty getting enough oxygen. The accompanying pain, a squeezing pressure in the chest called angina, can plague patients for years, and there are some for whom no surgery can provide relief. But a noninvasive shockwave machine could help prompt the growth of new blood vessels, restoring the heart’s oxygen supply and alleviating the pain.

In a clinical trial at three centers across the United States, cardiologists are testing the safety of the shockwave device, developed by Maryland-based Medispec. The “Cardiospec” machine is based on the same sound-wave technology used to break up kidney stones, but it requires only about one-tenth the energy. “Shock waves are acoustic waves that create pressure that can be focused,” says Medispec’s Gil Hakim, the company’s director of new product development. Direct that pressure toward the heart muscle with just the right intensity, and it causes the body to produce new blood vessels.

Researchers aren’t sure precisely why shockwaves have this effect–they believe that the pressure may induce a cascade of events that mimic wound-healing, recruiting undifferentiated cells to the area to build blood vessels. Preliminary studies show that about 70 percent of the patients who undergo the shockwave procedure experience somewhere between a 60 to 70 percent improvement in blood flow to their hearts.

“Patients with [recurring] angina consume a lot of medical care because they have multiple emergency visits, they have multiple angiograms, and their quality of life is extremely low,” says Amir Lerman, a cardiovascular specialist at the Mayo Clinic in Rochester, MN, who’s heading up the Cardiospec trial. And, he notes, the treatments available to these patients to date are short-term therapies that address the symptoms rather than the cause. “These patients currently don’t have any alternative solution. And we need to find one because they live a long time.”

The trial will recruit 15 patients–five each at the Mayo Clinic, the University of California at San Diego, and Albert Einstein Medical Center in Philadelphia–and it will consist of nine treatments applied over a nine-week period (three treatments per week during weeks one, five, and nine).

The Cardiospec technology has already been used to treat about 1,000 patients worldwide, in Europe, Canada, and other regions around the globe. And so far, it seems that about two to three years after the original treatment, patients can experience a relapse. Many patients who undergo treatment don’t change their exercise habits or diets, their blood vessels begin to narrow, and once again their hearts can’t get enough oxygen. “It’s like when patients have undergone a stenting procedure,” Hakim says. “That won’t necessarily be the only stent, because they develop another problem in another area in the heart.”

It’s not that the shockwave treatment has failed. Rather, a patient ends up with the same problem in a different region of his heart. “It’s like maintenance–after a few years, patients can be evaluated, checked again, and then retreated,” Hakim says.

The options available for so-called “refractory angina” patients, who have pain after surgery or aren’t candidates for surgery in the first place, are quite limited, says Timothy Henry, an interventional cardiologist at the Minneapolis Heart Institute who’s not involved in the trial. “We definitely need new options, and this is an interesting one. The preliminary data looks very good, it’s low risk. I think this is a really good option, but it needs to be tested,” Henry says.

Lerman and his collaborators hope to complete the safety trial in a few months, and Medispec is aiming for U.S. Food and Drug Administration approval by 2012. Hakim is hopeful that the technology can provide relief for patients who are now completely dependent on oral medications to stem the tide of their angina attacks. “On average, before starting the treatment, the patients took their medication around three times a day. After the therapy, they’re taking it around three times a week. It’s a marked improvement in their quality of life,” he says. “It’s not a cure, but it’s an improvement.”

Stuart Isett for The New York Times

Shawn Verrall waters his upside-down tomato plants with his daughter, Megan, in their Richmond, Wash., garden.

By KATE MURPHY

Published: May 19, 2010

IF pests and blight are wrecking your plants, it might be time to turn your garden on its head.

Erich Schlegel for The New York Times, Donald Rutledge, in New Braunfels,

Tex.,  put his buckets on pulleys to protect his plants from deer.

The Topsy Turvy Garden

Mark McAlpine made his own containers for his Ontario garden.

Growing crops that dangle upside down from homemade or commercially available planters is growing more popular, and its adherents swear they’ll never come back down to earth.

“I’m totally converted,” said Mark McAlpine, a body piercer in Guelph, Ontario, who began growing tomatoes upside down two years ago because cutworms were ravaging the ones he planted in the ground. He made six planters out of five-gallon plastic buckets, some bought at the Home Depot and some salvaged from the trash of a local winemaker. He cut a two-inch hole in the bottom of each bucket and threaded a tomato seedling down through the opening, packing strips of newspaper around the root ball to keep it in place and to prevent dirt from falling out.

He then filled the buckets with soil mixed with compost and hung them on sturdy steel hooks bolted to the railing of his backyard deck. “Last summer was really hot so it wasn’t the best crop, but I still was able to jar enough whole tomatoes, half tomatoes, salsa and tomato sauce to last me through the winter,” said Mr. McAlpine, who plans an additional six upside-down planters this year.

Upside-down gardening, primarily of leggy crops like tomatoes, cucumbers and peppers, is more common partly because of the ubiquity of Topsy Turvy planters, which are breathlessly advertised on television and have prominent placement at retailers like Wal-Mart, Walgreens and Bed Bath & Beyond. According to the company that licenses the product, Allstar Products Group in Hawthorne, N.Y., sales this year are twice last year’s, with 20 million sold since the planter’s invention in 2005. Not to be outdone, Gardener’s Supply and Plow & Hearth recently began selling rival upside-down planters. “Upside-down gardening is definitely a phenomenon,” said Steve Wagner, senior product manager for Plow & Hearth.

The advantages of upside-down gardening are many: it saves space; there is no need for stakes or cages; it foils pests and fungus; there are fewer, if any, weeds; there is efficient delivery of water and nutrients thanks to gravity; and it allows for greater air circulation and sunlight exposure.

While there are skeptics, proponents say the proof is in the produce.

Tomato and jalapeño seedlings sprout from upside-down planters fashioned out of milk jugs and soda bottles that hang from the fence surrounding the Redmond, Wash., yard of Shawn Verrall, a Microsoft software tester who blogs about gardening at Cheapvegetablegardener.com. Mr. Verrall turned to upside-down gardening last summer as an experiment.

“I put one tomato plant in the ground and one upside down, and the one in the ground died,” he said. The other tomato did so well, he planted a jalapeño upside down, too, and it was more prolific than the one he had in the ground. “The plants seem to stay healthier upside down if you water them enough, and it’s a great way to go if you have limited space,” he said.

While horticulturists, agronomists and plant scientists agree that pests and blight are less likely to damage crops suspended in the air, they said they are unsure whether growing them upside down rather than right-side up will yield better results.

“Growing things upside down seems like a fad to me, but I’m glad people are fooling around with it and hope they will let us traditionalist gardening snobs know what we’ve been missing,” said Hans Christian Wien, a horticulture professor at Cornell University in Ithaca, N.Y.

Judging from gardening blogs and Web sites, those fooling around with upside-down gardening are generally enthusiastic, particularly if they have planted smaller varieties of tomatoes.

“Bigger tomatoes are too heavy and put too much stress on the vine, causing it to twist and break,” said Michael Nolan, an avid gardener in Atlanta and a writer for Urbangardencasual.com, who has four upside-down planters also made out of five-gallon buckets in which he grows bushels of cherry and patio varieties of tomatoes as well as small pickling cucumbers.

Tomato varieties are labeled as either indeterminate or determinate, and horticulture experts recommend choosing indeterminate ones for upside-down gardens. Determinate tomato plants are stubbier, with somewhat rigid stalks that issue all their fruit at once, which could weigh down and break the stems if hanging upside down. Indeterminate types, by contrast, have more flexible, sprawling stems that produce fruit throughout the season and are less likely to be harmed by gravity.

When Mr. Nolan first tried upside-down gardening, he used the Topsy Turvy planters, which are made of polyethylene bags and look like Chinese lanterns gone wrong. But he was disappointed in the yield. “I far prefer using buckets,” he said, which hang from tall metal shepherd hooks bolted to the posts supporting his backyard deck. He paints his buckets bright colors, and plants herbs and marigolds in the top to help retain moisture.

Another, less decorative solution for preventing evaporation is to top the planters with mulch or simply cover them with a lid. Regardless, Mr. Nolan said, “The upside-down planters tend to dry out really fast, so I have to water a lot — probably once a day in the heat of the summer.”

Many gardeners reported that the thinner, breathable plastic Topsy Turvy planters ($19.98) dried out so quickly that watering even once a day was not enough to prevent desiccated plants. There were similar comments about the Plow & Hearth version ($12.95) and while the Gardener’s Supply upside-down planter ($19.95) has a built-in watering system, online reviewers said it is difficult to assemble.

In addition to plastic soda bottles, milk jugs and five-gallon buckets, upside-down planters can be made out of thick heavy-duty plastic trash bags, plastic reusable shopping totes, kitty litter containers, laundry hampers and even used tires. Web sites like Instructables.com and UpsideDownTomatoPlant.com show how it can be done, and YouTube has several how-to videos. Variations include building a water reservoir either at the top or bottom of planters for irrigation, cutting several openings in the bottom and sides for planting several seedlings and lining the interior with landscape fabric or coconut fiber to help retain moisture.

Donald Rutledge, a construction project designer and manager in New Braunfels, Tex., devised a triple-pulley system so he could easily hoist his nine upside-down planters 16 feet above the ground, away from ravenous deer. He made his planters out of five-gallon buckets four years ago, following instructions on the Internet. “The tomatoes and basil worked real well upside down, but the lettuce, peas and carrots weren’t so successful,” he said. “It’s been trial and error.”

This year, he put his plantings right-side up in the buckets to see if it makes any difference. He said his suspended garden started as an entertaining summer project for him and his three children but has become more of a scientific pursuit: “Is upside down better than right-side up? I’m guess I’m going to find out.”

Neuron transform: An astroglial cell from a mouse’s brain has been transformed into a type of neuron called an excitatory neuron. The green color marks a molecule specific to excitatory neurons, and the white indicates a molecule critical for synaptic plasticity, a key function in communication between neurons.     Credit: Christophe Heinrich

 

 

Transforming support cells in the brain into neurons might one day help repair damage from stroke or injury

 

 

MIT Technology Review, May 2010, by Courtney Humphries  –  Support cells in the brain called astroglia can be turned into functioning neurons, according to a study in this week’s Public Library of Science Biology. Researchers found that they could transform the cells into two different classes of neurons, and that the neurons could form connections with one another in a dish. Although the research is at an early stage, the finding suggests that scientists could someday recruit existing cells in the brain to repair the brain and spinal cord after a stroke, injury, or neurodegenerative disease.

The research team, from the Helmholtz Center and Ludwig-Maximilians University in Munich, had previously shown that it was possible to turn astroglia–star-shaped cells that provide structural support in the brain–into neurons by introducing genes called transcription factors into the cells using a virus. In that study, however, the neurons did not form functioning connections, or synapses. Now the researchers have demonstrated that astroglial cells taken from young mice can be transformed into synapse-forming neurons, and can be directed into two different major classes of neurons.

The addition of one specific genegenerated excitatory neurons, which promote activity in other cells. By adding a different gene, they generated inhibitory neurons, which dampen cell activity. In principle, “you could generate other types of neurons if you choose the appropriate factors,” says study coauthor Benedickt Berninger. For instance, he said, researchers could generate the dopamine-releasing neurons that are destroyed by Parkinson’s disease.

The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. Researchers have previously transformed skin cells into neurons, and one type of pancreatic cell into another. Marius Wernig, a coauthor of the skin cell study and a stem cell biologist at Stanford University, says there’s a growing awareness that it may not be necessary to erase a cell’s existing identity before giving it a new one.

Wernig says that the PLOS Biology paper offers a new strategy for creating neurons that complements the approach of using skin cells. Skin cells, he says, would be more useful for generating a patient’s own cells in a petri dish for transplantation, because a skin sample is easy to obtain. In contrast, this latest study “means that these astroglial cells could be converted in the brain” without the need for a transplant. Berninger says that one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain.

Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice.

Sweet power: Scientists implanted a glucose-powered device into the abdominal cavity of a rat and measured its performance for three months. The glucose device consists of electrodes made of compressed graphite discs containing enzymes that catalyze the oxidation of glucose. The electrodes sit inside a dialysis bag that keeps enzymes inside but lets glucose and oxygen flow through.    Credit: Joseph Fourier University, National Center for Scientific Research

An implanted biofuel cell may someday power medical devices

MIT Technology Review, May 2010, by Janelle Weaver  –  Scientists have implanted the first functional glucose biofuel cell in a living animal. Unlike batteries that supply power to implants, a power-generating device may not have to be surgically removed and replaced, because glucose is a potentially limitless source of energy.

The device uses enzymes to harvest energy from glucose and oxygen found naturally in the body. Past attempts at using such a device in animals have failed because the enzymes have required acidic conditions or were inhibited by charged particles in the fluid surrounding cells. But Philippe Cinquin and his team from Joseph Fourier University in Grenoble, France, overcame these obstacles by confining selected enzymes inside graphite discs that were placed into dialysis bags. Glucose and oxygen flowed into the device, but enzymes stayed in place and catalyzed the oxidation of glucose to generate electrical energy.

The team surgically implanted the device in the abdominal cavity of two rats. The maximum power of the device was 6.5 microwatts, which approaches the 10 microwatts required by pacemakers. The power remained around two microwatts for 11 days in one rat, and the other rat showed byproducts of glucose oxidation in its urine for three months, indicating that the device lasts at least that long. “This is a big breakthrough for the field of implantable biofuel cells,” says Shelley Minteer, an electrochemist at Saint Louis University.

“It’s quite an interesting paper that demonstrates for the first time that one can generate electrical power from body fluids,” says Itamar Willner, a biomolecular chemist at the Hebrew University of Jerusalem.

The technology could be used for a range of applications, such as neural and bone-growth stimulators, drug delivery devices, insulin pumps, and biosensors, says Eileen Yu, a chemical engineer at Newcastle University. But whether enzymes remain stable for a long period of time is a concern, she says. And the efficiency of transfer of electrons between enzymes and electrodes should be improved, she says.

Cinquin believes his team can improve its efficiency. “I’m optimistic that we will get tens of milliwatts in future versions,” he says.

The authors would next like to test the device for longer periods of time in larger animals, improve its design, and incorporate biocompatible materials. “If industry finds a willingness to enter into the technological development of biofuel cells, I’m sure the use of biofuel cells to power medical implants will materialize in a very short period of time,” Willner says.

Making Medicine Personal

MIT Technology Review, May 24, 2010  –  A number of scientists bared their genetic souls recently as part of the Personal Genome Project, a study at Harvard University Medical School. They were among the first of the eventually 100,000 volunteers who will agree to place their genetic profiles on the Internet.

Genetic profiling can provide information on what diseases may befall us. And knowledge of an individual’s genetic makeup may also help scientists figure out how to treat diseases—part of an emerging field known as personalized medicine.

As many doctors freely admit, says Julie Johnson, director of the Center of Phamacogenomics at the University of Florida (UF), prescribing medicine is “more of an art than a science.” Approved drugs work—but not 100 percent of the time, and not for 100 percent of the population. Some people have no response to certain drugs, and others experience severe side effects.

What determines whether a particular treatment is effective or leads to severe side effects is our genes, scientists believe. Personalized medicine holds the promise of tailored medical treatments based on genetic information, rather than a one-size-fits-all approach.

The UF center participated in studies on warfarin, a blood thinner prescribed for millions of Americans to prevent heart attack or clotting after a heart attack. Too little of the drug causes a risk of clotting, and too much can cause excessive bleeding. “There’s a very narrow window, and there’s a great deal of variability among patients,” says Johnson. “A lot of work in the past decade has uncovered several genes that help explain a great deal of that variability.” In 2007, the FDA cleared a genetic test for sensitivity to warfarin to help doctors prescribe the correct dosage, although the tests are not yet widely implemented.

The UF center is also focusing research on drugs prescribed for hypertension, in an attempt to find the genes that “will predict how much a person’s blood pressure will go down if they’re administered certain medicines,” says Johnson.

Speeding the Process

Part of what has contributed to the increasing interest in personalized medicine is the speed and cost of sequencing genomes. The first human genome took many years and millions of dollars to sequence. The price has already dropped into the thousands instead of millions of dollars, and it’s expected to continue to fall. The journal Science listed “faster, cheaper genome sequencing” as one of the top scientific advances in 2008.

These advances have increased the speed of research in the field. John Reed, the president and CEO of Burnham Institute for Medical Research, a center with campuses in San Diego, CA, and Orlando, FL, says that the Florida campus has engaged in major initiatives related to personalized medicine. While Burnham’s research has traditionally focused on cancer and on neurodegenerative and inflammatory diseases, the scientific team is expanding into obesity, diabetes, and metabolism research.

“We all have friends who can eat french fries every day and never gain weight, while the rest of us will have a hard time getting the belt to fit,” says Reed. “There are genetic differences in how we metabolize food—individual metabolic rates, hormone signaling—that’s all just being worked out.” Burnham is partnering with the clinical research institute at Florida Hospital, particularly the diabetes center, to engage in research on the metabolic systems of the patients there.

A related field of research involves investigating which chemicals can affect the actions of proteins, encoded by specific genes. This is a natural path to drug discovery, but it can also aid in genomic research. “A chemical probe can be used in basic research to help identify the role of a protein or a pathway, aiding in understanding the biology of a particular gene,” says Patrick Griffin, chair of Molecular Therapeutics at Scripps Florida, a campus of Scripps Research Institute headquartered in California.

The National Institutes of Health (NIH) funds four molecule-screening centers in the United States to rapidly test a library of chemicals against specific proteins. Scripps Florida operates one of the four centers.

Burnham operates a second of those NIH molecule-screening centers at both its California and Florida research centers. Currently, its screening output can tackle half a million chemicals in one day, but the new system being developed in Orlando will be able to handle as many as 2.2 million chemicals a day.

The fields of genome research and rapid drug discovery are coming together to enhance each other, says Reed. “We’ll be able to, with far more accuracy, define for whom a drug is really going to work, and to avoid a lot of trial and error that we experience when we’re confronted with a health issue.” He and other researchers in the field see a time not too far in the future when understanding individual genomes will lead to better, more effective medical treatments for everyone.