Archives: 5/2008

05 08Nanoworms Tumor Targeting, Immune System Evading NanowormsScientists from UC San Diego, UC Santa Barbara, and MIT developed metal nanoparticles, that can, because of their shape and polymer coating, evade the body’s immune system, allowing for free movement around the body. Additionally, a coating of a special peptide F3 molecule allows the nanoparticle to hone in on tumor cells. Perhaps this is the complimentary technology that is required to make the Kanzius Machine effective against tumors?

The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.
“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor [Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team --ed.]. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”
In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.
“Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,” said Sailor. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”
The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.
“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors,” said Ji-Ho Park, a UC San Diego graduate student in materials science and engineering working in Sailor’s laboratory.

Press release: UC San Diego Researchers Target Tumors with Tiny ‘Nanoworms’ …

paper chip x220 Paper based Diagnostic Microfluidic DevicesMIT Technology Review is reporting that researchers at Harvard are using paper as the building block material for creating small microfluidic devices, potentially allowing to make cheap disposable diagnostic tests.

A pinprick of blood or drop of urine soaked up at the edge of the Whitesides device moves naturally through the paper, in much the way that wine will spread through a paper napkin. But the paper is treated with a hydrophobic polymer, which directs the liquid along prescribed channels. Once the liquid reaches the wells at the ends of the channels, it interacts with reagents, turning the paper different colors. The colors can be matched to those on a color key, much as they are in a pH test. One test design that looks like a miniature, three-branched, geometric tree might have wells at the end of two branches for a glucose assay and one at the end of the third for a protein assay, for example.
The design dispenses with expensive components common in conventional microfluidic devices: chemical reactions that color parts of the paper replace sophisticated sensors and analyzers, while using paper’s natural capillary action to absorb liquids avoids the need for external pumps or power sources. Diagnostics for All–a spinoff cofounded by Whitesides and Harvard visiting scholar Hayat Sindi, with the support of partners from MIT–is commercializing the technology.
Instead of etching channels into a material, as most microfluidics designers do, Whitesides and Sindi were able to take advantage of the network of channels inherent in paper; the hydrophobic polymer simply seals off the channels that the researchers don’t want to use. “What’s really clever about this system is that they’ve actually patterned the whole volume of the substrate,” Folch explains. “The paper itself forms a network of capillaries.”

More at MIT Tech Review

35463pep Scientists Discover Heat Sensing RegulatorNeuroscientists at Johns Hopkins are working on identifying molecular mechanisms behind the sensation of heat in food and spiciness. Their latest research was published in the latest Cell.
From the press statement by Johns Hopkins:

“Pain sensitivity increases during inflammation or injury and we want to know what molecules are involved in pain sensation when sensitivity is elevated,” says Xinzhong Dong, Ph.D., an assistant professor of neuroscience at Hopkins.
The ability to sense temperature heat and spice is controlled by the TRPV1 protein channel found on the surface of certain nerve cells. In an inactive state, TRPV1 channels remain closed-there is no pain sensation. However, when noxious heat-temperatures above 108 degrees Fahrenheit-or capsaicin-the main ingredient in “hot” peppers-activates a TRPV1 channel, ions flow through, depolarizing the nerve to create an electrical current that sends pain signals to the brain.
“The interesting thing about this channel is it’s not always constant,” says Dong, whose team set out to find proteins that modulate TRPV1’s action. They found the Pirt protein,phosphoinositide interacting regulator of TRP, and named it for its ability to regulate the TRPV1 channel.
To better understand how Pirt works, the researchers made mice that lacked Pirt and tested their ability to respond to heat. The mice were placed on a hot surface and monitored for how long it took them to scurry off. Mice lacking Pirt responded significantly slower than normal mice.
The team then exposed one hind paw to capsaicin and found that mice lacking Pirt did not lick their paws as long as normal mice, suggesting that without Pirt, they were compromised in their ability to sense the spice of capsaicin. The researchers also tried mustard oil on the hind paw and found mice lacking Pirt licked for about the same amount of time as normal mice. These observations suggest that Pirt’s action is specific to capsaicin and not other chemicals.
To figure out whether Pirt directly affects TRPV1 channel action, the researchers measured electrical currents generated by TRPV1 in single nerve cells with or without Pirt. They exposed some nerves to noxious heat-108 degrees Fahrenheit-and some nerves to capsaicin and compared currents generated in each cell. Cells containing Pirt generated stronger currents in heat and spice than cells lacking Pirt, leading the researchers to conclude that Pirt is required for a full pain response to both heat and spice.
Further research revealed that Pirt interacts with yet another molecule in the cell, a so-called acidic phospholipid, allowing access to TRPV1. According to Dong, through this phospholipid Pirt somehow changes the TRP channel, perhaps by opening it wider, or maybe by causing it to stay open longer. And the result is elevated pain sensitivity.
Exactly how Pirt regulates the TRPV1 channel isn’t yet clear, says Dong. “The goal is to find molecules that specifically affect the pain pathway, but not other nerves,” he says. “We’re looking for genes specifically turned on in pain-sensing neurons. If we find them and can target them with new drugs, we will be able to treat pain without unfavorable side effects.”

Press release: Too Hot To Handle! Scientists Identify Heat Sensing Regulator…
Abstract: Pirt, a Phosphoinositide-Binding Protein, Functions as a Regulatory Subunit of TRPV1 Cell, Vol 133, 475-485, 02 May 2008

5687gam AudiOdyssey DJ Simulator for Visually Impaired or Not
A new computer game called AudiOdyssey, developed by MIT and Singaporean students, makes it possible “for visually impaired people to play the game on a level field with their sighted friends.”
From the product page:

The user stars as Vinyl Scorcher, an up-and-coming DJ, on his quest to get club patrons dancing. Swinging the Nintendo Wii controller to the beat, Vinyl lays down the various component tracks of a song, and keeps the party jumping. If he does an especially good job, he can even freestyle! But beware – if dancers get too rowdy, they’re likely to bump into the turntables, messing up Vinyl’s tracks. Think you have what it takes?
AudiOdyssey was developed with four research goals:

  • The visually-impaired and the sighted can enjoy the same level and quality of gameplay
  • Navigate game’s menus with ease and efficiency approaching that of conventional UIs
  • Create a fun and natural control scheme using the Wiimote
  • An engaging game that relies more on high quality audio than visuals

  • Free download here: AudiOdyssey
    MIT press release: Singapore-MIT game lets visually impaired share the fun…

    5654oo Successful Gene Expression Profiling Performed on EmbryosA team from Monash University in Australia has developed a way to identify, and do a DNA analysis of embryos, which should improve the success of IVF procedures in the future.
    Dr. Gayle Jones, co-author of the study, and a senior research scientists at the Monash Immunology and Stem Cell Laboratories said the following:

    “One of the major stumbling blocks to worldwide acceptance of a single embryo transfer policy is the lack of highly predictive criteria to select the single most viable embryo within a cohort. The ability to use objective, measurable criteria rather than subjective observations, such as morphology, should improve the predictive value and provide sufficient confidence for clinicians to shift towards single embryo transfers for all patients without a concomitant drop in pregnancy rates. This would effectively reduce multiple pregnancies, which is a priority in the field of assisted reproductive medicine at present.”

    More from Forbes
    Article abstract in Human Reproduction: Gene expression profiling of human oocytes following in vivo or in vitro maturation
    Image credit: Wellcome images: Secondary oocyte of human during in vitro fertilisation, viewed with light microscope using Nomarski optics. The small cell bottom left is a polar body….

    1210697241990.low resolution Medtronic 3D Vision Line Gets First FDA ApprovalsMedtronic received FDA approval for the company’s wireless implantable defibrillators, the first devices in a product line that also includes pacemakers and resynchronization therapy pacemakers.

    Leading into Heart Rhythm 2008, the pre-eminent worldwide gathering of cardiologists specializing in electrophysiology, Medtronic, Inc… announced U.S. Food and Drug Administration (FDA) approval of the first wave of cardiac rhythm disease management therapies under the new Vision 3D™ portfolio, which will comprise a full line of implantable cardioverter-defibrillators (ICDs), cardiac resynchronization therapy-defibrillators (CRT-Ds), pacemakers and cardiac resynchronization therapy-pacemakers (CRT-Ps) to address the needs of patients with arrhythmias, heart failure and those at risk of sudden cardiac arrest (SCA). The portfolio’s first ICD and CRT-D devices will be commercially available in the coming months…
    In addition to other Medtronic proprietary features, Vision 3D introduces automaticity with Complete Capture Management™, which provides confidence in patients’ safety by continuously and automatically adjusting to changing patient needs. Complete automaticity provides physicians flexibility during in-office device checks and may also reduce battery drain.
    “For the first time, we have access to sophisticated defibrillators with complete automaticity to capture what’s happening in three chambers of the heart and adjust the device’s stimulation to the body’s physiologic needs,” said Anne Curtis, M.D., FHRS, FACC, FAHA, chief of the Division of Cardiology and director of Cardiovascular Services at the University of South Florida. “This also gives us insight into key trend data to help better manage the patient’s condition, rather than simply inform us how the implanted device is operating.”
    Other state-of-the art Medtronic innovations available in the Vision 3D portfolio include:

  • Automaticity with Complete Capture Management™, which provides confidence in patients’ safety by continuously and automatically adjusting to changing patient needs.
  • Conexus® Wireless Telemetry, the industry’s most-used system, is available on all Vision 3D ICDs and CRT-Ds.
  • Medtronic’s PainFREE™ strategy to stop fast heartbeats, which has been clinically proven to eliminate three out of four shocks with painless therapy, potentially improving patient quality of life.
  • Medtronic’s MVP® mode, or Managed Ventricular Pacing, which allows doctors to dramatically reduce unnecessary pacing to the right ventricle (RV, or the heart’s lower right chamber).
  • OptiVol® Fluid Status Monitoring, a Medtronic feature that measures intrathoracic impedance in heart failure patients.
  • The following “backgrounder” about its Vision 3D portfolio was distributed by Medtronic to the media:

    Read this doc on Scribd: Vision 3D Backgrounder


    Press release: Medtronic Announces FDA Approval of New Vision 3D Wireless Implantable Cardiac Devices …

    67868ii SEPET Extracorporeal Liver Assist Device OKed for Pivotal Clinical TrialSEPET™ Liver Assist Device, a blood purification technology designed by Arbios Systems, Inc., a Pasadena, CA company, has been given FDA’s Investigational Device Exemption (IDE) status. The clearance paves the way for the company to begin a pivotal clinical trial. The device, a filter with special qualities, is designed for use with a standard blood dialysis system. We first reported about SEPET™ Liver Assist Device back in April 2005.
    More about the technology, and the planned trial:

    The SEPET™ Liver Assist Device is a novel blood purification therapy designed for use with a standard blood dialysis system. It comprises a sterile, single-use, disposable cartridge containing microporous hollow fibers with unique permeability characteristics. When a patient’s blood is passed through these fibers, blood plasma of specific molecular weight and size is expressed through the micropores, thereby cleansing the blood of harmful impurities (i.e., hepatic failure toxins such as ammonia, as well as various mediators of inflammation and inhibitors of hepatic regeneration). These substances would otherwise progressively accumulate in the patient’s bloodstream during liver failure, accelerating damage to the liver and other organs, including the brain and kidneys, and suppressing the ability of liver cells to function and to proliferate or regenerate.
    SEPET™ is further designed to retain in the circulating bloodstream numerous larger, beneficial molecular weight blood proteins, including a powerful promoter of liver regeneration, Hepatocyte Growth Factor (HGF), various immunoglobulins, such as IgG, IgM, and others, and various complement species that are important for retaining active immune protection against infection (which often exacerbates liver failure). SEPET™ also retains most of the blood clotting factors, which are important for preventing bleeding—another common and potentially lethal complication of liver failure…
    There are three segments to the pivotal trial design. During the first segment of the trial, 5 non-randomized patients will be treated with SEPET to allow us to validate the patient selection criteria, clinical protocol, case report forms, and other trial related documents. During the second segment of the trial, we expect to enroll 116 patients in this randomized, controlled phase of the trial. This segment is targeted to achieve the co-primary endpoints, which are 1) the percentage of patients achieving improvement in hepatic encephalopathy ("HE") grade by a minimum of two grades by the end of Day 7 in the SEPET treatment group versus the standard medical care group, using a 1:1 randomization between the two groups; and 2) the 30-day transplant free survival rate in all patients (i.e. control and treatment groups) who do reach a two grade Pending review and approval by the Data Safety Monitoring Board, the third segment would permit the size of the trial to be increased by an additional 52 patients, if the co-primary efficacy endpoints are reached or have not reached statistical significance but have shown a positive trend. If the co-primary endpoints of the trial are reached upon completion of segment two, extension of the trial into segment three may result in the achievement of statistical significance of one or more secondary endpoints of the trial relating to clinical, functional, and reimbursement advantages for SEPET-treatment over standard medical care.
    To be a candidate for the pivotal trial, a patient must have chronic liver disease and be experiencing an acute episode that results in hospitalization with an HE grade of between II and IV. In addition, the patient must not be responding satisfactorily to standard medical care (e.g. fluid replacement, antibiotics, lactulose) for 20 to 26 hours prior to randomization. Patients contraindicated for a liver transplant (e.g. advanced liver cancer patients and drinking alcoholics) are excluded from the trial.

    sepetdiag SEPET Extracorporeal Liver Assist Device OKed for Pivotal Clinical Trial
    Product page: SEPET™ Liver Assist Device…
    Press release: ARBIOS RECEIVES APPROVAL FROM THE FDA TO INITIATE PIVOTAL TRIAL FOR SEPET™ LIVER ASSIST DEVICE…

    26454mo How Dangerous is Moon Dust?At the National Space Biomedical Research Institute, scientists are studying the human physiologic response to prolonged exposure to lunar dust, the particles of which might pose a threat to human lungs:

    During the Apollo lunar missions in the late 1960s and 1970s, the clingy particles were easily transported via spacesuits into the lunar lander following moonwalks. The amount of dust inside the vehicle was so great some astronauts reported they could smell it.
    Even though there were no known illnesses due to exposure, lunar dust is a concern because it has properties comparable to that of fresh-fractured quartz, a highly toxic substance. However, the Apollo flights lasted only a few days. During the proposed return to the moon, astronauts will be exposed to lunar dust for longer periods of time, including missions that could last months.
    Due to the moon’s reduced gravity and the size of its dust particles, the respiratory system’s process to remove unwanted matter may not work as efficiently as it does on Earth. “In the moon’s fractional gravity, particles remain suspended in the airways rather than settling out, increasing the chances of distribution deep in the lung, with the possible consequence that the particles will remain there for a long period of time,” Prisk said.
    The lungs are a highly sensitive organ because of the large surface area that delivers oxygen molecules through a thin membrane directly to the blood. The health risk to astronauts increases as dust particles go deeper into the lungs.
    To conduct the research, scientists take measurements during flights on NASA’s Microgravity Research Aircraft. These airplanes are used to provide short periods of reduced- and zero-gravity during a series of steep climbs and descents.
    “During the portions of the flight in which gravity is reduced to levels seen on the lunar surface, we inject particles into a mouthpiece through which the study participants breathe,” Prisk said. “Subjects breathe in and out, and we measure how the particles behave and how many end up inside the lung.”
    Prisk said the research flights have been beneficial so far. “With the reduced-gravity flights, we’re improving the process of assessing environmental exposure to inhaled particles,” he said. “We’ve learned that tiny particles (less than 2.5 microns) which are the most significant in terms of damage, are greatly affected by alterations in gravity.”
    The next step is to investigate the risks and determine ways to limit exposure.

    Press release: Astronaut health on moon may depend on good dusting…

    Co-sponsored by Medgadget, the 2nd Annual DiabetesMine™ Design Challenge, “a competition designed to foster innovation in diabetes design and encourage creative new tools that will improve life with diabetes,” is gathering up steam. As we have reported before, the contest is looking for unique, practical, and novel design ideas that may one day be applied to real products for diabetics. The winners of the design challenge will receive both prize money and consulting time with design firm IDEO. How much money? Now even more of it!
    Please note the following newly announced updates to the competition:

  • increased prize money (we have an additional $200 from DexCom and an additonal $1000 from two anonymous sponsors, bringing the total to $3200)
  • we’d now like to open up to “paper” submissions as well as YouTube videos (requirements are a 2-3 page written “elevator pitch” plus supporting graphics).
  • extension of the submission deadline to midnight PST on Monday, June 16, 2008. Winners will be announced on Friday, June 20, 2008.
  • Press release: DiabetesMine™ Announces Diabetes Design Contest to Foster Innovation for Life with Diabetes; Good Design can Transform Life for Diabetics…
    More at Diabetes Mine…