Gene-Targeted Therapy Might Help Prevent Paralysis

Spinal cords of rats shown 24 hours after cervical injury. The rat whose spinal cord is shown in A...
Spinal cords of rats shown 24 hours after cervical injury. The rat whose spinal cord is shown in A received no active treatment whereas the rat whose spinal cord is shown in B was treated to suppress Abcc8, demonstrating a noticeable reduction in hemorrhage.
(Courtesy J. Marc Simard, M.D., Ph. D.)


Suppressing the gene for an ion flux regulatory molecule protected rats against paralysis following spinal cord injury, researchers said, a finding that could have similar implications in humans.

An antisense oligonucleotide, given intravenously 15 minutes after rats' spinal cords were crushed, improved trunk and hind-limb function compared with a sham treatment when the animals were tested six weeks later, according to J. Marc Simard, MD, PhD, of the University of Maryland in Baltimore, and colleagues.

The experiment was one of several implicating the Sur1 receptor protein, which helps control sodium and calcium fluxes into and out of cells, as being critical to loss of neuronal function after injury. The findings were reported online in Science Translational Medicine.

Simard and colleagues suggested that therapies targeting Sur1 expression, combined with glibenclamide (to block preexisting ion channels), appear to be "a promising strategy for prevention of the devastating sequelae of spinal cord trauma in humans."

Sur1 is shorthand for sulfonylurea receptor 1, a name denoting its original discovery as a target for some diabetes drugs.

It has never been clear why total paralysis frequently results when the human spinal cord is injured but not severed: the trauma evidently triggers processes that cause spinal neurons to die off or otherwise cease working over time.

As a result, researchers have been looking for ways to interrupt those process and salvage spinal cord function.

One of those nerve-killing processes appears to be the hemorrhaging that frequently follows a spinal injury, which results from a slow but catastrophic failure of capillaries around the injury site, according to Simard and colleagues.

Previous research indicated that expression of calcium channels regulated by Sur1 surges in capillary endothelial cells during these secondary hemorrhages and is at least partly responsible for them.

Simard and colleagues confirmed the importance of Sur1 in this process with tests on spinal cord tissue taken from human patients who died a few days after spinal trauma. Sur1 proteins were detected in penumbral tissues around the site of injury, but they were less common at the epicenter and absent in remote areas.

Messenger RNA associated with the gene for Sur1, Abcc8, was also more abundant in penumbral regions, but not farther away.

The researchers also studied the effects of spinal cord injury on mice whose Abcc8 gene was silenced and compared them with injuries to normal mice.

Relative to the normal animals, those with Sur1 expression that had been knocked down showed much less secondary hemorrhaging, and it reached its maximum extent within 30 minutes. In the normal mice, hemorrhaging and necrosis continued to spread for 24 hours.

In a final set of experiments, rats had their spinal cords crushed in a standardized way, and an antisense oligonucleotide was administered 15 minutes later, designed to block translation of Abcc8.

Five types of neuromotor function tests -- assessing the animals' trunk stability, walking and rearing ability, and balance after six weeks -- all showed performance "consistently better" in the treated animals than in rats given a nonsense oligonucleotide.

Simard and colleagues found that glibenclamide, a Sur1 antagonist, also improved rats' performance in the spontaneous rearing test following the same type of injury.

Both the antisense drug and glibenclamide led to 75% reductions in spinal cord lesion volume six weeks after the injury, compared with sham-treated animals, the researchers reported.

"Future studies will be needed to determine the therapeutic window for Abcc8 antisense as well as for Sur1 inhibitors such as glibenclamide," Simard and colleagues concluded.

U.S. Treasury Unveils The New $100 Federal Reserve Note

Officials from the U.S. Department of the Treasury, the Federal Reserve Board and the United States Secret Service today unveiled the new design for the $100 note. Complete with advanced technology to combat counterfeiting, the new design for the $100 note retains the traditional look of U.S. currency.



U.S. Treasury Unveils The New $100 Federal Reserve Note
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Comment On This ArticleBy Bureau of Engraving and Printing on Wednesday, April 21, 2010
Filed Under: Banknotes
Officials from the U.S. Department of the Treasury, the Federal Reserve Board and the United States Secret Service today unveiled the new design for the $100 note. Complete with advanced technology to combat counterfeiting, the new design for the $100 note retains the traditional look of U.S. currency.



“As with previous U.S. currency redesigns, this note incorporates the best technology available to ensure we’re staying ahead of counterfeiters,” said Secretary of the Treasury Tim Geithner.

“When the new design $100 note is issued in TBD, the approximately 6.5 billion old design $100s already in circulation will remain legal tender,” said Chairman of the Federal Reserve Board Ben S. Bernanke. “U.S. currency users should know they will not have to trade in their old design notes when the new notes begin circulating.”



The redesigned $100 note includes two new advanced counterfeit-deterrent security features, in addition to effective security features from the previous design. The features are easy for consumers and merchants to check when verifying authenticity.

The blue 3-D Security Ribbon on the front of the new $100 note contains images of bells and 100s that move and change from one to the other as you tilt the note.

The Bell in the Inkwell on the front of the note is another new security feature. The bell changes color from copper to green when the note is tilted, an effect that makes it seem to appear and disappear within the copper inkwell. “The new security features announced today come after more than a decade of research and development to protect our currency from counterfeiting.

To ensure a seamless introduction of the new $100 note into the financial system, we will continue global public education of retailers, financial institutions and industry organizations to ensure that consumers and merchants are aware of the new security features,” said Treasurer of the United States Rosie Rios.

“For 145 years, the men and women of the United States Secret Service have worked diligently to protect the integrity of U.S. currency from counterfeiters,” said Director Mark Sullivan. “During that time, our agency has evolved to keep pace with the advanced methodologies employed by the criminals we pursue. What has remained constant in combating counterfeiting, however, is the effectiveness of consumer education initiatives that urge merchants and customers to examine the security features on the notes they receive.”

Although less than 1/100th of one percent of the value of all U.S. currency in circulation is reported counterfeit, the $100 note is the most widely circulated and most often counterfeited denomination outside the U.S. “The $100 is the highest value denomination that we issue, and it circulates broadly around the world,” said Michael Lambert, Assistant Director for Cash at the Federal Reserve Board. “Therefore, we took the necessary time to develop advanced security features that are easy for the public to use in everyday transactions, but difficult for counterfeiters to replicate.”

“The advanced security features we’ve included in the new $100 note will thwart potential counterfeiters from producing high-quality fakes that can fool consumers and merchants,” said Larry R. Felix, Director of the Treasury’s Bureau of Engraving and Printing. “Protect yourself -- it only takes a few seconds to check the new $100 note and know it’s real.”

The new design for the $100 note retains three effective security features from the previous design: the portrait watermark of Benjamin Franklin, the security thread, and the color-shifting numeral 100. The new $100 note also displays American symbols of freedom, including phrases from the Declaration of Independence and the quill the Founding Fathers used to sign this historic document. Both are located to the right of the portrait on the front of the note.

The back of the note has a new vignette of Independence Hall featuring the rear, rather than the front, of the building. Both the vignette on the back of the note and the portrait on the front have been enlarged, and the oval that previously appeared around both images has been removed.

For a more detailed description of the redesigned $100 note and its features, visit www.newmoney.gov where you can watch an animated video, click through an interactive note or browse through the multimedia center for images and B-roll.

Also, visit www.newmoney.gov for information on how to order free training materials for cash handlers, or you may download the materials directly from the Web site. The training materials for the $100 note are available in 25 languages.

The New $100 Note will be available starting February 10, 2011.

Heather Locklear Hit-and-Run Arrest!

Actress Heather Locklear is in trouble with the law again after a hit-and-run arrest Saturday morning. Locklear allegedly hit a no parking sign and failed to stop and report the damage before driving home. Luckily, there were no other people involved in the accident.




Heather Locklear was arrested after police followed a trail of debris from the accident scene back to her home in Ventura County, CA. After discovering damage to Locklear’s black BMW, police charged her with misdemeanor hit-and-run.

“While Locklear was technically arrested, she was not handcuffed or taken to a station because it was just a misdemeanor charge,” Ventura County Sheriffs Dept spokesman Ross Bonfiglio told People. “She was cooperative, but I can’t give any information about any statements she made. She was cited and released. She signed a document stating she would make a court appearance.”

Heather Locklear is already serving a three year probation from a reckless driving incident in September, 2008. Locklear was originally charged with DUI in that arrest, but later pleaded no contest to the lesser charge.

Somebody lock down this lady’s keys before she ends up killing someone!

Former Mayor Kwame Kilpatrick Is Found Guilty

Kwame Kilpatrick faces jail for violating probation terms that have allowed him to remain free and living on his high horse in Texas, a judge ruled today. ”He’s facing incarceration,” Wayne County Circuit Judge David Groner told prosecutors during Kilpatrick’s criminal probation hearing. “You know that.”
Groner ruled that Kilpatrick violated the terms of his probation because of his failure to disclose all of his assets as well as not reporting money he received from tax refunds for tapping political funds, and money he received from a $240,000 loan.
Just so you all know your tax return is considered an asset.Kilpatrick also hasn’t made a $240,000 restitution payment due by 4:30 p.m. today. Failure to pay put him around $280,000 behind on court-ordered payments on $1 million promised to the city when he took a plea bargain in 2008 to avoid trial on charges stemming from the infamous text message scandal. Damn Kilpatrick I guess you don’t have common sense. – Courtney L.

It's About Time: Kate Gosselin Booted Off Dancing with the Stars

Kate Gosselin was sent packing on Dancing With the Stars Tuesday.

After their fifth consecutive brutal week, she and partner Tony Dolovani could not stave off the inevitable. When her fate was announced, she was speechless.

"I need a minute," she said, tearfully. "I am so honored to have been here. It was a good experience. I cannot wait to watch the rest of these people Monday."

In the bottom two for the second time this season, despite being decent Monday night and all season long, were Pamela Anderson and Damian Whitewood.


Kate Gosselin reacts to her Dancing with the Stars ouster.

Tony Dovolani, who has clashed repeatedly with her, then said he is "proud of Kate. I know she gets a lot of criticism out ... She has eight kids and is a single mom ... she showed up every single day. I thought she danced beautifully."

Now she can show up every day at home, right Jon Gosselin?

If nothing else, it was a classy exit and a fairly long run. To her fan base, Kate said "Thank you for believing in me probably more than I believed in myself."

Schefter: Roethlisberger to be suspended 6 games; Steelers looking at trade options

We've certainly had plenty of discussion about Ben Roethlisberger but this remains a significant story. Adam Schefter is reporting that sources are indicating that Ben Roethlisberger is facing a 6 game suspension to start the season. Schefter indicated that if certain unreported conditions are met, the suspension would eventually be reduced to 4 games. He has tweeted and retweeted some interesting information. For instance:

Pittsburgh has begun contacting teams to trade Ben Roethlisberger for a top 10 pick. At least one team considering it. Story far from done.

The next 24 hours will be especially interesting with any potential Steeler deal.

He also retweeted an interesting comment:

This tweeter was on to something last night. RT @bdischy: Coincedence that PITT has 5 National TV games but 0 of their first 6 games?

Do you believe in a conspiracy like this? Is the 6 games potentially reduced to 4 sufficient? Any ideas where Big Ben ends up? And if the Steelers do get a top 10 pick, are they drafting Jimmy Clausen?

Official Press Release after the jump...




COMMISSIONER ROGER GOODELL notified Pittsburgh Steelers quarterback BEN ROETHLISBERGER today that he 1) must undergo a comprehensive behavioral evaluation by medical professionals and 2) will be suspended without pay for the first six games of the regular season for conduct detrimental to the NFL in violation of the league's Personal Conduct Policy.

After consultation with Commissioner Goodell, Steelers President ART ROONEY and the commissioner informed Roethlisberger by telephone today of the two-step approach that is designed to hold Roethlisberger accountable for his conduct and provide him an opportunity to change his behavior and establish himself as a responsible individual.

In a letter to Roethlisberger, Commissioner Goodell said that Roethlisberger must adhere to any counseling or treatment that is recommended by the professional evaluators to help him make better decisions and avoid situations that can cause legal or other problems. A professional behavioral evaluation is mandatory for anyone that has violated the NFL Personal Conduct Policy. Roethlisberger may not attend any team off-season activity after today until he has completed the evaluation and the evaluating professionals confirm with the commissioner that Roethlisberger may resume football activities. If so cleared, Roethlisberger will be able to participate in training camp and preseason games this summer.

The commissioner said he would review Roethlisberger's progress under the plan prior to the start of the regular season and consider whether to reduce the suspension to four games. Failure to cooperate and follow the plan could result in a longer suspension, the commissioner added.

"The Personal Conduct Policy makes clear that I may impose discipline ‘even where the conduct does not result in conviction of a crime' as, for example, where the conduct ‘imposes inherent danger to the safety and well being of another person'," Commissioner Goodell stated in his letter to Roethlisberger. "As the District Attorney concluded, the extensive investigatory record shows that you contributed to the irresponsible consumption of alcohol by purchasing (or facilitating the purchase of) alcoholic beverages for underage college students, at least some of whom were likely already intoxicated. There is no question that the excessive consumption of alcohol that evening put the students and yourself at risk. The Personal Conduct Policy also states that discipline is appropriate for conduct that ‘undermines or puts at risk the integrity and reputation of the NFL, NFL clubs, or NFL players.' By any measure, your conduct satisfies that standard."

Commissioner Goodell said his review of the matter included the extensive volume of material released by the Georgia Bureau of Investigation and the Milledgeville Police Department; public comments by and a private conversation with Georgia District Attorney Fred Bright; comments and recommendations of Roethlisberger's representatives; a personal interview with Roethlisberger on April 13; dialogue with current players, former players, the NFL Players Association, and others; and information learned by the NFL office in the course of examining the Milledgeville matter.

Other excerpts from Commissioner Goodell's letter:

•"I recognize that the allegations in Georgia were disputed and that they did not result in criminal charges being filed against you. My decision today is not based on a finding that you violated Georgia law, or on a conclusion that differs from that of the local prosecutor. That said, you are held to a higher standard as an NFL player, and there is nothing about your conduct in Milledgeville that can remotely be described as admirable, responsible, or consistent with either the values of the league or the expectations of our fans."

•"Your conduct raises sufficient concerns that I believe effective intervention now is the best step for your personal and professional welfare."

•"I believe it is essential that you take full advantage of the resources available to you. My ultimate disposition in this matter will be influenced by the extent to which you do so, what you learn as a result, and a demonstrated commitment to making positive change in your life."

•"In your six years in the NFL, you have first thrilled and now disappointed a great many people. I urge you to take full advantage of this opportunity to get your life and career back on track."
In addition to the discipline imposed on Roethlisberger, league policy requires that NFL teams remit to the league a portion of a suspended player's salary starting with the second suspension in a year for violations of the personal conduct or drug policies. The second such suspension in a year results in the club being assessed 25 percent of the suspended player's forfeited salary to a maximum of $200,000. Prior to the Steelers trading him to the New York Jets, wide receiver Santonio Holmes was suspended for four games for violating the substance abuse program.