Posts Tagged ‘Medicine’

A Second Skin For A Second Chance

Professor Meital Zilberman of Tel Aviv University’s Department of Biomedical Engineering has developed a special dissolvable fiber loaded with antibiotics which can be made into a wound dressing.

Although this may seem to be a simple concept, skin functions in a complex way which is not easily mimicked.

Skin, Prof. Zilberman explains, serves a number of vastly different purposes. “Wound dressings must maintain a certain level of moisture while acting as a shield,” she says. “Like skin, they must also enable fluids from the wound to leave the infected tissue at a certain rate. It can’t be too fast or too slow. If too fast, the wound will dry out and it won’t heal properly. If too slow, there’s a real risk of increased contamination.”

Severe burns are a particularly nasty variety of dermal damage. About 70% of people with severe burns die from infections, not from their actual wounds. In a valiant effort to help patients survive the healing process nurses must change dressings often to prevent infection by cleaning the wounded areas. This new wound dressing can change all that by eliminating the need for constant redressing and by applying high levels of antibiotics precisely where they are needed.

Unlike oral antibiotics, locally-applied antibiotics can target and kill harmful bacteria before they enter the body to cause further infection, sepsis, or death. “People who suffer from large burns don’t usually die from the condition itself. The fatal culprits are the secondary bacterial infections that invade the body through these vulnerable burned areas,” says Prof. Zilberman.

The new TAU dressing inhibits bacterial growth and is biodegradable, which helps doctors avoid constant wound cleaning and  redressing, allowing the body to do the work on its own. “When administered at the wound, a doctor can give relatively high but local doses of antibiotics, avoiding any toxicity issues that arise when the same amount of antibiotic passes through the body,” explains Prof. Zilberman, who worked on this research with Jonathan Elsner, her Ph.D. student.

The only sad part of this news is how early in the development phase it is in right now.

Prof. Zilberman is now starting the early stages of clinical trials on animal models. So far, her wound dressing has passed physical and mechanical tests in vitro and in bacterial inhibition tests in the laboratory. She is also seeking a strategic partner to co-develop the research and take it to the commercial stage.

If this revolutionary new wound dressing survives the clinical stage then it may begin appearing in hospital near you within a few short years.

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Researchers have found that the insulin signaling pathways in worms have a direct bearing on their lifespan. This research is particularly interesting because humans and worms share very similar insulin signaling pathways.

Over a decade ago, the first part of this research led to some positive news as researchers found that certain mutations involved in the insulin pathways can greatly extend lifespan in worms.

“In the early 90s, we discovered mutations that could double the normal life span of worms,” Kenyon said. Those mutations effected insulin signals. Specifically, a mutation in a gene known as daf-2 slowed aging and doubled life span. That longer life depended on another “FOXO transcription factor” called DAF-16 and the heat shock factor HSF-1.

Unfortunately, the recent results show that adding sugar to the worm diet has the opposite effect.

By adding just a small amount of glucose to C. elegans usual fare of straight bacteria, they found the worms lose about 20 percent of their usual life span. They trace the effect to insulin signals, which can block other life-extending molecular players.

Here is the technical aspect of the results:

In fact, glucose makes no difference to the life span of worms that lack DAF-16 or HSF-1, they show. Glucose also completely prevents the life-extending benefits that would otherwise come with mutations in the daf-2 gene.Ultimately, worms fed a steady diet containing glucose show a reduction in aquaporin channels that transport glycerol, one of the ingredients in the process by which the body produces its own glucose. “If there is not enough glucose, the body makes it with glycerol,” Kenyon explained. That glycerol has to first get where it needs to go, which it does via the aquaporin channels.

There are a few ways in which the result from studying worms affects us as humans.

A diet with a low glycemic index seems like a safe bet for now. One of the scientists was alarmed enough with the data to make serious changes to her diet:

As an aside, Kenyon says she read up on low-carb diets and changed her eating habits immediately — cutting out essentially all starches and desserts — after making the initial discovery in worms. The discovery was made several years ago, but had not been reported in a peer-reviewed journal until now.

Another area of concern is medicine. Current drugs may be offering treatment which carry as of yet unknown long term side effects. Fortunately, as is the case with anti-depressant medication, science is continually advancing to make our lives better and this research will undoubtedly result in better life saving medicines.

She says the findings may also have implications for drugs now in development for the treatment of diabetes, which are meant to block glucose production by inhibiting glycerol channels. The new findings “raise a flag” that glycerol channels might be doing something else, she says, and that drugs designed to block them might have a downside.

A long term study recently found a connection between consuming two servings of diet soda daily and a significant decline in kidney function. How do different types of artificial sugars factor into these results? Is there any connection between these two studies?

Aging in humans is far more complex than in worms.

“Although we do not fully understand the mechanism by which glucose shortens the life span of C. elegans, the fact that the two mammalian aquaporin glycerol-transporting channels are downregulated by insulin raises the possibility that glucose may have a life-span-shortening effect in humans, and, conversely, that a diet with a low glycemic index may extend human life span,” the researchers write. Kenyon also points to recent studies that have linked particular FOXO variants to longevity in several human populations, making the pathway the first with clear effects on human aging.

Glucose and the insulin signaling pathways are probably just one piece in a complex puzzle explaining the aging process. With every piece of the puzzle that gets illuminated and understood we come one step closer to allowing science an opportunity to stop aging.

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Eva Redei, the David Lawrence Stein Professor of Psychiatry at Northwestern’s Feinberg School has published new research which explains why antidepressants don’t work for so many people.

There are two prevailing theories about the causes of depression. One is that depression can be caused by stressful life events and the second is that depression results from an imbalance in neurotransmitters. However, medications based on those theories are treating effects, not causes.

Most animal models that are used by scientists to test antidepressants are based on the hypothesis that stress causes depression. “They stress the animals and look at their behavior,” she said. “Then they manipulate the animals’ behavior with drugs and say, ‘OK, these are going to be good anti-depressants.’ But they are not treating depression; they are treating stress.”

That is one key reason why current antidepressants aren’t doing a great job, Redei noted. She is now looking at the genes that differ in the depressed rat to narrow down targets for drug development.

She said another reason current antidepressants are often ineffective is that they aim to boost neurotransmitters based on the popular molecular explanation of depression, which is that it’s the result of decreased levels of the neurotransmitters serotonin, norepinephrine and dopamine. But that’s wrong, Redei said.

Redei examined the genes involved in both stress and depression. Of the 254 genes related to stress and the 1275 genes related to depression there is an overlap of only 5 genes.

“This overlap is insignificant, a very small percentage,” Redei said. “This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes as depression does.”

If current medications are only treating effects then research should be focused on finding and treating the causes.

In the second part of the study, Redei found strong indications that depression actually begins further up in the chain of events in the brain. The biochemical events that ultimately result in depression actually start in the development and functioning of neurons.

“The medications have been focusing on the effect, not the cause,” she said. “That’s why it takes so long for them to work and why they aren’t effective for so many people.”

Her animal model of depression did not show dramatic differences in the levels of genes controlling neurotransmitters functions. “If depression was related to neurotransmitter activity, we would have seen that,” she said.

Unfortunately, although we now know those theories are wrong, we still do not have a theory that is right.

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As with many scientific discoveries, there is an interesting back story here.

The story begins with a biologist, Robert Silverman of the Cleveland Clinic Foundation in Ohio, investigating if prostate cancer is caused by a virus.

Actually, the story begins a bit earlier than that. Scientists have known that viruses can cause cancer since the early 20th century.

In 1909 Peyton Rous discovered that a virus could cause sarcomas in chickens. For discovering the Rous Sarcoma Virus, Dr. Rous was awarded the Nobel Prize in 1966. This discovery led directly to the discovery of cellular oncogenes (genes that cause cancer) by Bishop and Varmus, which also was rewarded with a Nobel Prize.

Subsequently, numerous other human cancers have been associated with viral infections. The most important of these is Burkitt’s lymphoma. Burkitt’s lymphoma comes in three varieties: one form is endemic to sub-Saharan Africa and is most likely caused in large part by infection with a virus called Epstein-Barr Virus (EBV, which also causes mono), one form is sporadic (as opposed to endemic), and one form is associated with immunodeficiencies such as AIDS. The endemic form of Burkitt’s lymphoma typically causes a large, painful jaw mass, while the sporadic form more commonly involved the intestines. Interestingly, another name for EBV is Human Herpesvirus-4 (HHV-4). EBV, or HHV-4, also causes nasopharyngeal carcinoma in southeast Asia (and elsewhere). It is clear that there is a real connection between viruses and cancer.

Now back to Robert Silverman, who discovered a new retrovirus called XMRV.

The retrovirus was very similar to MLV, a group of viruses that can cause cancer and neurological and immunological diseases in mice. Silverman found XMRV in a subset of prostate tumours, and more recent research found a stronger correlation between XMRV and aggressive prostate tumours.

We should pause for a moment and explain the difference between a virus and a retrovirus. A virus is a very simple organism – basically a protein shell containing a little DNA. Viruses need to find hosts because they lack the tools to multiply on their own.

Cells also contain DNA, but cells (especially those of complex organisms such as humans) have ridiculous amounts of DNA. Most of the instructions in DNA used by cells on a daily basis are for creating proteins. Since mistakes are most likely to occur proportionally to how often DNA is copied, a system using RNA minimizes copying by only duplicating the specific section of DNA needed to build a specific protein. RNA is slightly different than DNA on a molecular level, so cellular machinery can respond to it but not to DNA. A cell which needs a particular protein manufactured goes through the following (simplified) steps:

  1. A portion of DNA is translated into RNA.
  2. RNA is sent to the endoplasmic reticulum.
  3. The specified protein is built.

A standard virus hijacks the cell’s machinery by inserting DNA, which gets translated into RNA, which is then made into the specified protein; only in that case the protein is the virus.

Retroviruses are more insidious. They contain RNA rather than DNA. When a retrovirus attacks a cell, the RNA gets translated into DNA, which then gets incorporated into the cell’s own genome. Rather than hijacking the cellular machinery for their own nefarious plans, they Borg the cell. From then on, every time the cell multiplies it is bringing the virus along with it. Our genome is littered with scars from ancient battles with retroviruses which may have fundamentally shaped us into what we are today.

Alright, enough with the interruptions already.

Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, Nevada, asked Silverman to see if there was a connection to chronic fatigue syndrome.

Mikovits asked Silverman to analyze the blood samples of 101 CFS patients and 218 healthy controls. The authors detected XMRV DNA in the immune cells of 67% of the CFS patients but in only 3.7% of healthy controls. The authors also showed that the virus was able to spread from infected immune cells to cultured prostate cancer cells and that the virus’s DNA sequence was more than 99% similar to the sequence of the virus associated with prostate cancer. The findings were published in Science.

So far, although the results are encouraging, there has only been one pilot study completed. The magic which makes science work is verification and duplication of results.

William Reeves, principal investigator for the Centers for Disease Control and Prevention (CDC)’s CFS public health research programme, says the findings are “unexpected and surprising” and that it is “almost unheard of to find an association of this magnitude between an infectious agent and a well-defined chronic disease, much less an illness like CFS”.

But Reeves is cautious. “Until the work is independently verified, the report represents a single pilot study,” he says. According to Reeves, the CDC is already trying to replicate these findings. He also notes that CFS is a heterogeneous disease and likely arises from a combination of many factors.

The Wall Street Journal has a heartbreaking example of the suffering caused by CFS:

Ms. Whittemore-Goad says she was a regular school girl, playing sports and involved in school activities, until the age of 10, when she became ill with a monolike virus that she couldn’t shake. She said doctors first told her parents that the illness was psychological, that she had school phobia and was under stress from her parents. “We kept searching for an answer,” says Ms. Whittemore-Goad, who says lymph nodes in her groin were so painful that her brothers and sisters used to have to carry her upstairs. She was diagnosed at age 12 with chronic-fatigue syndrome.

Over the years, doctors have treated her symptoms, like intense headaches and severe pain, but the illness persists. She has had her gallbladder, spleen, and appendix removed because they became infected. She tried an experimental drug that she says gave her relief for years, but she then started experiencing side effects and had to stop taking it. Recently the illness has become worse; she began suffering seizures and can no longer drive.

Go read the whole thing.

If this virus is the cause of CFS, diagnosis and detection can be done with a simple blood test. Antiretroviral therapies designed in the fight against HIV are under investigation as a potential cure. The story is not yet over but we remain hopeful that this breakthrough represents the real deal for sufferers of CFS.

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Pfizer’s Whistleblowers

The problems at Pfizer which led to the record $2.3 billion settlement were revealed by whistleblowers. Unfortunately, it was not just individual sales representatives who were pushing for sales based on off label uses. Sales managers, who have the responsibility of noticing and preventing these abuses, were the ones pushing for these sales to earn bigger bonuses.

One of the sales reps was Stefan Kruszewski, a psychiatrist. He did not merely disagree with the promotion of unapproved off-label usage of Geodon (an anti-psychotic drug), but actively went and researched it.

Kruszewski didn’t just say no. He went and checked the research and saw Geodon could have serious cardiac side effects not mentioned by the salesmen, who boasted of its relative safety, according to his lawyer, Brian Kenney. And he noticed that Pfizer was paying his peers to promote the drug to other psychiatrists.

He got a lawyer who specializes in these kinds of cases, and they presented their information to the government. Several years earlier, John Kopchinski (also a sales rep) did not fare as well. He joined with Kruszewski and also presented his information to the government.

So did John Kopchinski, who sold Pfizer’s arthritis drug Bextra but not as aggressively as the bosses wanted. They told the sales force to pitch it for post-surgical pain, acute pain, migraines and a host of other conditions for which the drug had been rejected by the U.S. Food and Drug Administration, says Kopchinski’s lawyer, Erika Kelton.

Nor would he advise doctors to boost the recommended dosage to two, four, even eight times the amount approved, though other salespeople did.

“The sales managers were having us do what was blatantly illegal,” Kopchinski told the BBC. Those who did were rewarded financially. He refused, was fired and spent the next six years depleting his retirement funds.

There are a total of 6 whistleblowers, and the awards they are getting range from $2.3 million to $51 million.

Pfizer may really be working hard behind the scenes to make sure all their divisions, subsidiaries, and related sales teams comply with the law, but this is not the first time something like this has happened.

To resolve claims it promoted off-label uses of Neurontin, an anti-seizure drug, Warner-Lambert, owned by Pfizer, paid $430 million in 2004, and Pfizer said it would institute a compliance program.

There’s a systemic problem going on, because the Pharmacia & Upjohn Co. division involved in this most recent case were involved in the same type of off-label promotion nonsense before.

Three years later, Pfizer’s Pharmacia & Upjohn Co. divisions agreed to pay almost $35 million to settle charges related to the human-growth hormone Genotropin. Among the allegations was that the drug was being promoted as an anti- aging treatment.

That same subsidiary has again pleaded guilty, this time as part of the overall settlement with Pfizer for its promotion of Bextra.

Part of Pfizer’s growth strategy involves acquiring other companies. These companies may bring with them an ingrained corrupt corporate culture which takes some time to purge. It is important to note the difference between a company promoting a safe off-label use for a drug, versus an off-label use specifically prohibited by the FDA because of the problems it causes.

We are still hesitant to label Pfizer as evil because killing customers is not a good corporate strategy, what with the big fines and bad publicity eating into profits. Big Tobacco is not a good counter example because none of their products are safe for use, on-label, off-label, or otherwise. They do a lot of good, and huge companies like it will run into the “left hand doesn’t know what the right hand is doing” problems at one point or another. However, although Pfizer can technically blame the Parmacia & Upjohn subsidiary here, it is imperative they have a thorough internal review and toughened compliance system put in place before they even consider any new acquisitions.

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The only way we could think of to go beyond a top 10 list is…

a top 20 list!

Here are important developments in the field of biotechnology and medicine, which will help the sick or disabled return to full capacity and extend our lives. Some of these are in clinical trials while others are still strictly in the research phase.

  1. Decay Fighting Microbes
  2. Artificial Lymph Nodes
  3. Asthma Sensor
  4. Cancer Spit Test
  5. Biological Pacemaker
  6. Prosthetic Feedback
  7. Smart Contact Lens
  8. Speech Restorer
  9. Absorbable Heart Stent
  10. Muscle Stimulator
  11. Nerve Regenerator
  12. Stabilizing Insoles
  13. Smart Pill
  14. Autonomous Wheelchair
  15. Gastrointestinal Liner
  16. Liver Scanner
  17. Nanoscale Adhesive
  18. Portable Dialysis
  19. Walking Simulator
  20. Rocket Powered Arm

Popular Mechanics has the details on all these items plus a few cool images and diagrams.

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The MC1R (melanocortin-1 receptor) gene produces melanin in humans. A variant of this gene present in redheads may be responsible for an increased sensitivity to pain. Non-redheads may carry this variant nor is it 100% guaranteed that a redhead will have it.

Many people will encounter anesthesia for the first time in their everyday lives at the dentist’s office. Administering too much anesthesia can have serious consequences so dentists are hesitant to go above recommended guidelines. Someone with a heightened pain sensitivity will likely never want to set foot in a dental office again after single procedure requiring anesthesia. Postponing dental care will likely make the problem worse and cause even more pain down the road.

“Redheads are sensitive to pain,” said Dr. Daniel Sessler, an Outcomes Research Department chair at The Cleveland Clinic, in Cleveland, Ohio, who is one of the authors.

“They require more generalized anesthesia, localized anesthesia. The conventional doses fail. They have bad experiences at the dentist and because of the bad experiences, they could avoid dental care.”

Sessler, an anesthesiologist, began studying redheads’ sensitivity to pain after hearing chatter from colleagues.

“The persistent rumor in the anesthesia community was that redheads were difficult to anesthetize,” Sessler said. “They didn’t go under, had a lot of pain, didn’t respond well to anesthesia. Urban legends usually don’t start studies, but it was such an intriguing observation.”

This led to two studies. In 2004, research showed that people with red hair need 20 percent more general anesthesia than blonds and brunettes.

A 2005 study indicated that redheads are more sensitive to thermal pain and are more resistant to the effects of local anesthesia.

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Healing Wounds With Nanodiamonds

“This study introduces the concept of nanodiamond-mediated release of therapeutic proteins,” said Dean Ho, assistant professor of biomedical engineering and mechanical engineering at the McCormick School of Engineering and Applied Science. Ho led the research. “It’s a tricky problem because proteins, even small ones like insulin, bind so well to the nanodiamonds. But, in this case, the right pH level effectively triggers the release of the insulin.”

Nanodiamonds will hold onto insulin tightly under normal pH conditions. If they are place in an alkaline environment (pH above 7) the insulin loses its grip and is released.

That’s all well and good but why would you want to put insulin onto a would site?

Insulin accelerates wound healing by acting as a growth hormone. It encourages skin cells to proliferate and divide, restores blood flow to the wound, suppresses inflammation and fights infection. Earlier investigations have confirmed an increase in alkalinity of wound tissue, due to bacterial colonization, to levels as high as pH 10.5, the pH level that promoted insulin release from the nanodiamonds in the Northwestern study.

Now it makes sense.

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There are two general types of prostate cancer, and one of them is very aggressive. Unfortunately for some men, that means surgery is no longer an option by the time it gets noticed. Fortunately, some great forward strides have been made on this front at the Mayo Clinic to give these men a fighting chance.

Dr. Kwon called Dr. Allison and designed the trial together. The idea: use androgen ablation or hormone therapy to ignite an immune approach — a pilot light — and then, after a short interval of hormone therapy, introduce an anti-CTLA-4 antibody that acts like gasoline to this pilot light and overwhelms the cancer cells. MDX-010 (now called Ipilimumab) is the clinical antibody being tested in the Mayo trial.

This has been tested on two patients so far, with very good results, but some caution is in order.

Both investigators are quick to point out that the outcomes in these two patients need to be validated in further studies. Plans are already underway for extended trials at Mayo Clinic to determine the dosage to optimize this therapy and explain how this combined treatment actually works.

“It’s important for us to understand the mechanism of favorable response in these patients,” says Dr. Blute. “This could have significant implications for other forms of cancer, including hormone-sensitive forms, such as breast and ovarian cancer.

Go read the source material for a detailed account of the patients experiences, and to learn a little more about the treatment.

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Here’s a whole bunch of “just around the corner” advances which will have an impact on health and medicine within the next 5 – 10 years. Some are already undergoing clinical trials.

The list:

  1. Transcranial Magnetic Stimulation (TMS) In TMS, magnetic pulses created by a metal coil attached to the scalp generate small electrical currents in the brain; these stimulate nerve cells in areas involved in depression—without harming surrounding gray matter.
  2. Stem Cell ScaffoldTo pinch-hit for missing tissue at an injury site, stem cells need a scaffold to grow on—but artificial materials such as plastic won’t do, since the body flags and rejects them as foreign sub­stances.
  3. Instant DiagnosisThe device he’s designed detects thousands of different biological molecules in a single exhalation, creating a snapshot of the breath’s contents that could signal the presence of illnesses, from cancer to cystic fibrosis.
  4. Pre-emptive Strike Against CancerDerived from acids in plants, CDDO-Im activates natural enzymes that remove toxic compounds from cells—compounds that might otherwise create DNA mutations that lead to cancer.
  5. Implantable Nanowire If Zhong Lin Wang has his way, routine blood-pressure checks at the doctor’s office will soon be a thing of the past. The Georgia Institute of Technology physicist has designed an implantable nanowire that measures pressure fluctuations constantly, enabling patients to track their vital stats from home.
  6. Superbug ZapperArizona State physicist K.T. Tsen has developed the ultimate multipurpose treatment tool: a superfast infrared laser that zaps bacteria and viruses without harming surrounding tissue.
  7. Targeted DeliveryTo help patients avoid side-effect doldrums, researchers at Philips’s pharmaceutical division are developing the medical equivalent of a targeted missile-delivery system.
  8. Bloodstream Bot – A mosquito-size robot developed by Oded Salomon, an engineer at Israel’s Technion Institute, may be able to pull off these surgical feats without making large incisions—so recuperation is much faster.
  9. EKG UntetheredWake up in the morning, stick a featherweight patch on your chest and tackle your day with the assurance that computers are keeping a constant eye on your ticker.
  10. Nano Cancer FightersThe particles have substances on their surfaces that make them home in on the cancer—one type contains a peptide that binds to proteins found in a tumor’s vessel linings.

Read the whole article for all the juicy details.

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