Antibiotic Booster Adjuvants: Allies in Fight Against Resistant Bacteria

As drug-resistant bacteria continue to challenge the existing armamentarium of antibiotics and scant new options emerge from the pipeline, scientists and clinicians are exploring a new strategy that may make existing drugs more effective and prevent new resistant strains from emerging.

They are seeking so-called antibiotic adjuvants. Just like adjuvants used for improving the immunogenicity of vaccines, these compounds enhance the action of antibiotics. They may do so through a variety of mechanisms, including by weakening the bacteria themselves, making them more vulnerable to antibiotics, or by interfering with bacterial mechanisms of antibiotic resistance. Teams working in this area have recently published or presented work highlighting promising antibiotic adjuvants—some found among drugs currently used for other applications, others derived from compounds in ocean environments. _JAMA

Anti-Diarrheal Drug Loperamide Boosts Minocycline Potency

Combining common antibiotics with additional compounds could make previously resistant bacteria more susceptible to the same antibiotics. ‘Resuscitation’ of existing antibiotics has the potential to make infections caused by multidrug-resistant bacteria easier to control, reducing antibiotic usage and levels of antimicrobial resistance, say scientists presenting their work at the Society for General Microbiology’s Spring Conference in Dublin this week.

Researchers from University College Dublin (UCD) studied a variety of bacteria that are frequently associated with hospital-acquired infections, including Pseudomonas, Klebsiella, Enterobacter and Staphylococcus. Bacterial samples were collected from hospital patients and from these, strains that showed resistance to a commonly prescribed antibiotic – ciprofloxacin - were selected for study.

The team tested ciprofloxacin in combination with one of five different ‘adjuvant’ compounds against these bacteria, to determine which combinations, if any, were more effective than treatment with ciprofloxacin alone. Results showed that all five adjuvant compounds increased the efficacy of ciprofloxacin; making it more active against the bacteria by up to six-fold. .

...The team believes that adjuvant therapy could revolutionize the way that antibiotics are used nowadays. “Hopefully this work will allow antibiotics to be incorporated into treatment regimes and administered in more effective ways,” said Dr Martins. “As well as extending the lifespan of current antibiotics, this approach could ultimately reduce levels of antimicrobial resistance in hospitals as well as in the community, allowing hard-to-treat bacterial infections to be successfully controlled,” she said. _SGMNews_via_SD

From the abstract of a Feb 2011 paper:

The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising. One approach to combat this growing problem is the use of combination drug antibiotic adjuvant therapy, which potentiates the activity of antibiotics....Adjuvant therapies include antibiotic combinations, synergy between antibiotics and nonantibiotics, inhibition of resistance and molecules that alter the physiology of antibiotic-insensitive cells, such as those in biofilms.... _NIHPubmed

The combination drug Augmentin can be consider as a forerunner of this new class of combination, anti-resistance antibiotics. The clavulinic acid in augmentin blocks a penicillinase enzyme that would otherwise inactivate the amoxicillin antibiotic.

As stated previously on Al Fin, bacteria are shifty, but humans have brains. Perhaps the global increase in antibiotic multi-resistance will spur more humans to use the brains they have to find solutions to the problem.

Building Two Pillars of SENS

Aging Damage	Discovery	SENS Solution
Cell loss, tissue atrophy	19551	Stem cells and tissue engineering (RepleniSENS)
Nuclear [epi]mutations (only cancer matters)	19592, 19823	Removal of telomere-lengthening machinery (OncoSENS)
Mutant mitochondria	19724	Allotopic expression of 13 proteins (MitoSENS)
Death-resistant cells	19655	Targeted ablation (ApoptoSENS)
Tissue stiffening	19586, 19817	AGE-breaking molecules (GlycoSENS); tissue engineering
Extracellular aggregates	19078	Immunotherapeutic clearance (AmyloSENS)
Intracellular aggregates	19599	Novel lysosomal hydrolases (LysoSENS)

The "seven pillars of SENS anti-aging strategies" are shown in the table above, with a timeline of the discovery of their importance shown in the image below.

Important progress has recently been made on two of the pillars of SENS: Correcting for mutant mitochondria, and an improved clearing of cellular junk.

First, correcting human mitochondrial mutations:

Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases. Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears March 12, 2012 in the peer-reviewed journal Proceedings of the National Academy of Sciences. _esciencenews

More at the link.

Next, clearing cellular trash aggregates:

A University of Michigan cell biologist and his colleagues have identified a potential drug that speeds up trash removal from the cell's recycling center, the lysosome.

The finding suggests a new way to treat rare inherited metabolic disorders such as Niemann-Pick disease and mucolipidosis Type IV, as well as more common neurodegenerative diseases like Alzheimer's and Parkinson's, said Haoxing Xu, who led a U-M team that reported its findings March 13 in the online, multidisciplinary journal Nature Communications.

"The implications are far-reaching," said Xu, an assistant professor of molecular, cellular and developmental biology. "We have introduced a novel concept—a potential drug to increase clearance of cellular waste—that could have a big impact on medicine." _UMich News

More at the link.

Both of these developments will require a number of years to perfect and shape into useful therapies. But as noted, improved therapies in either domain would provide hope for slowing the ageing process, and for treating many of the degenerative scourges of human existence.

The SENS Foundation has worked to promote research in the seven areas pictured above. And at least partially due to the efforts of SENS, more researchers and funding agencies are picking up the same themes.

Cross-posted to Al Fin Longevity

Let Johns Hopkins Take You to the Next Level of Body Mods

Why Have a Face Like This?:

When You Can Have a Face Like This?:

Keeping up with the Cardassians
Johns Hopkins bio-scientists have developed new biomaterials that will let you shape your face however you want. Here's more:

A new biomaterial may help surgeons rebuild the delicate soft structures of the human face, like the cheeks, after a disease or injury has caused disfigurement. The material, which is half synthetic and half biological, can be injected under the skin as a liquid, massaged into shape, and then permanently "locked" by exposure to light.

...It's a blend of hyaluronic acid—a biological material already used as a soft-tissue implant—and polyethylene glycol, a synthetic material. The blend is a liquid polymer that can be injected—thus avoiding the need for surgery. Once injected, the material can be sculpted into the necessary shape. When exposed to light of specific wavelengths, the messy tangle of polymer chains in the liquid implant rearrange into a stable, crosshatched form, stiffening the implant.... _TechnologyReview

Get the picture? Just mix the material, inject it under the skin, mould it into the shape you want, then shine a light on your work to hold its shape permanently -- or until you want to move on to something new.

The treatment was developed to help repair deformities from facial injuries and congenital conditions. But use your imagination for just a moment, and you will see that a lot more is possible.

This means big changes for patients suffering from facial disfiguration, a highly visible injury that can have social consequences. But that's just the most obvious use. If the material becomes a commercial product, we could see a wealth of potential customers among the extreme body-modification set. After all, the idea of reliably adding semi-permanent Klingon-like bumps to your face with a simple injection (a far less risky and expensive process, perhaps, than full-on plastic surgery) will definitely interest some people. _FastCompany

The Johns Hopkins approach will be used to alter the shape of the face. If you need to permanently change the texture or shade of your surface skin layer, you will need to take a different approach. But for under-the-skin shape changes -- should you wish to keep up with the Cardassians, for example -- the Johns Hopkins approach may be your ticket.

If you are thinking just a bit further out, you might imagine an injectible material made of intelligent gel material -- such as was discussed in yesterday's posting. Facial (or other) implants that can change their shape on the fly, while also acting as brain augments. Breasts, tummies, buttocks, or muscles that can grow larger or smaller, for example. Use your futuristic imagination. Or, if you prefer, you can have a face like the person pictured up top, today.

In Chernobyl, 60 Year Old Men Appear "Not a Day Over 30"

18March2011 Brian Wang has more on this story

"Radiation is good for you," one of them tells me. "Every year I get younger," says another. And another: "I work here so when I come home glowing my wife will think I'm a god."

A particularly hearty-looking man who works as a janitor asks me, "How old do you think I am?"

"Sixty," he answers himself....he looks not a day past 30. _Outside

As of January of this year, Chernobyl is now open to tourism. Over most of what is now the Chernobyl wildlife haven, radiation levels have returned near normal. The wild animal population is thriving, and the people there do not seem to be doing so badly themselves. Particularly so long as they have an ample supply of homemade vodka.

Residents of Chernobyl are not the only ones who claim health benefits from low dose exposure to ionizing radiation. Skim through the research regarding "radiation hormesis" referenced here and here, and you may begin to develop a bit of healthy skepticism toward the "zero tolerance policy" of modern environmental protection law toward low level radiation.

More on hormesis:

Hormesis is the term used to describe biological phenomena that are often adverse or detrimental but become beneficial when applied at low levels. The concept of biological hormesis is as important as that of homeostasis for the survival of the organism. The basic biological trait is the organism�s ability to resist and adapt appropriately to both internal and external stresses, and the hallmark of aging is the organism�s inability to withstand stress. The hormetic phenomenon in aging is characterized as beneficial responses to stress through the physiological adaptations, as exemplified in lifespan extension by irradiation and calorie restriction. Thus, hormesis in aging is the biological adaptive function to resist or blunt the age-related deleteriousness. Such a remarkable biological hormetic effect was shown experimentally by exposing mice to a low dose of gamma irradiation, which extended the lifespan of mice rather than shortening by turmorigenesis. The plausible explanation on this interesting radiation hormesis is that the irradiated mice were able to resist better, because the mild radiation itself is the most effective factor in conditioning for the activation of adaptation. In response to stress, an organism is expected to go through three distinct phases: alarm reaction, resistance phase, and exhaustion phase. According this schema, the adaptability can be developed during the resistance period. This notion is in line with the evolutionary view on the survival for the fittest theory, for which the only possible way to attain the survivability is through the organism�s metabolic and defensive adaptation to deleterious stress. _InnoVita

More on hormesis and ageing from an abstract in Ageing Research Reviews:

Hormesis in aging is represented by mild stress-induced stimulation of protective mechanisms in cells and organisms resulting in biologically beneficial effects. Single or multiple exposure to low doses of otherwise harmful agents, such as irradiation, food limitation, heat stress, hypergravity, reactive oxygen species and other free radicals have a variety of anti-aging and longevity-extending hormetic effects. Detailed molecular mechanisms that bring about the hormetic effects are being increasingly understood, and comprise a cascade of stress response and other pathways of maintenance and repair. Although the extent of immediate hormetic effects after exposure to a particular stress may only be moderate, the chain of events following initial hormesis leads to biologically amplified effects that are much larger, synergistic and pleiotropic. A consequence of hormetic amplification is an increase in the homeodynamic space of a living system in terms of increased defence capacity and reduced load of damaged macromolecules. Hormetic strengthening of the homeodynamic space provides wider margins for metabolic fluctuation, stress tolerance, adaptation and survival. Hormesis thus counter-balances the progressive shrinkage of the homeodynamic space, which is the ultimate cause of aging, diseases and death. Healthy aging may be achieved by hormesis through mild and periodic, but not severe or chronic, physical and mental challenges, and by the use of nutritional hormesis incorporating mild stress-inducing molecules called hormetins. The established scientific foundations of hormesis are ready to pave the way for new and effective approaches in aging research and intervention. _ARR

How much is too much, when it comes to radiation? That is difficult to say, at lower doses. Certainly if it is possible to build resistance against radiation and other sources of normal wear and tear, wouldn't most people want to do so?

A dangerous dose is hard to pin down. Worldwide, for most people, those daily microrems add up to about 360 millirems per year. Scientists agree that humans can safely handle 1,000 a year. Astronauts on the International Space Station receive 18,000 millirems of cosmic radiation over six months—but it's once in a lifetime, so it's seen as an acceptable, voluntary risk. But edge that up to 30,000 millirems and you're looking at what caused increased cancer rates among the blast survivors of Hiroshima and Nagasaki. And yet animals can handle even more than this: large mammals and birds are generally safe with 36,000 per year, small ones with even higher doses, and reptiles with higher still. The more complex the animal, the more sensitive it is. _Outside

Of course, animals spend more time outside under the ionizing radiation of the sun, than most modern humans. Perhaps the natural radiation protection exhibited by animals is a manifestation of hormesis?

As long as government-sanctioned science shies away from the topic of "safe levels of low level radiation," we may find it difficult to learn about this topic. With government becoming the largest financier of scientific research, human science is falling into something of a rut. Government bureaucracies are by nature conservative and self-serving. Naturally the science which such bureaucracies are willing to finance and publish, will be the kind of science which justifies the existence and mission of such bureaucracies. They're the government. They're here to help you. Or else.

How will we all survive after the house of cards crashes down? If there is life after a Chernobyl apocalypse, perhaps there could even be life after mega-government breakdown? It may be time for individuals to begin planning for interesting times ahead.

See you in Chernobyl?

Poor, Bare, Forked Animals Begin to Decipher Epigenome

NIH
The epigenome is the system of genome modifiers that guide gene expression. Epigenetics determines whether a cell will be a brain cell or a liver cell, even though both cells possess the same genome. Some preliminary results are beginning to come in from the US NIH's modENCODE program.

Sarah C.R. Elgin, PhD, the Viktor Hamburger Distinguished Professor in Arts & Sciences, who led the Washington University lab that is part of one of the modENCODE teams offers an explanation.

“We learned many things from the Human Genome Project,” Elgin says, “but of course it didn’t answer every question we had!

“Including one of the oldest: We all start life as a single cell. That cell divides into many cells, each of which carries the same DNA. So why are we poor, bare, forked creatures, as Shakespeare [Al Fin: Lear ActIII SceneIV] put it, instead of ever-expanding balls of identical cells?

“This work,” says Elgin, “will help us learn the answer to this question and to many others. It will help us to put meat on the bones of the DNA sequences.” _WUNewsroom

Wikipedia

The epigenetic code that determines whether genes are silenced or expressed consists of chemical modifications to the DNA, to “tails” that hang off the histones, or other packaging proteins.

“ENCODE and modENCODE are much more complicated projects than the Human Genome Project,” Elgin says, “because the DNA sequence is pretty much the same in every cell type, whereas the chromatin structure is different in every cell type. In fact we believe it is the chromatin structure that differentiates one cell type from another.

“That means we can’t just do one genome for the organism. We have to do every different cell type to get a complete picture of the organism, and that’s a daunting prospect.” _WU

The research relies upon the most advanced bio-research and computing technologies. The amount of data generated is staggering, and far beyond what an unaided human could organise and comprehend.

But this is the beginning of the true meat of genetics. Sure, they are looking at worms and fruit flies now. But humans and all human symbionts and parasites are on the list to be comprehensively studied. The knowledge to be gained will provide unimaginable benefits.

Boys Should be Breast-Fed Until at Least Age 6

Startling new research from Australia demonstrates that boys -- but not girls -- should be breast-fed until at least age 6, to achieve optimal academic performance.

Breast feeding improves later academic performance in boys but appears to have no such effect in girls.

Wendy Oddy at the Telethon Institute for Child Health Research in Subiaco, Western Australia, and colleagues, examined whether having been breastfed affected the test scores of over 1000 10-year-olds.

Studies have suggested that children who were breastfed have higher IQs than those who were not, but few separated out boys and girls. Mothers who breastfeed are on average wealthier and more educated, so Oddy's team accounted for these factors.

Boys who were mainly breastfed for at least six months [years ... per Al Fin Nutritional Institute] scored 9 per cent higher in mathematics and writing tests, 7 per cent higher in spelling and 6 per cent higher in reading, compared with boys fed with formula milk or breastfed for shorter periods. There were no significant differences in results for girls.

"We know that breast milk contains the optimal nutrients for development of the brain and central nervous system," says Oddy, but the gender differences were surprising.
Hormone link

Oddy points out that other studies have suggested boys are more vulnerable to stress and adversity during critical periods of brain development. She speculates this could be because girls seem to be protected by higher levels of oestrogen during childhood. She says the improved academic performance of boys could be explained by oestrogen in breast milk having similar neuro-protective effects.

Some studies have suggested that fatty acids uniquely present in breast milk explain research showing that it can help babies become more intelligent. Whether or not these fatty acids help in boosting IQ may be linked to the presence of certain gene variants involved in their processing.

A large randomised trial conducted by Michael Kramer at McGill University in Montreal, Canada, concluded that prolonged breastfeeding was linked to higher IQ and academic ratings by teachers in Belarussian children at age 6... _NS

Al Fin specialists in childhood nutrition recommend that boys be breast-fed until at least age 26, if not longer. You can never be too safe when it comes to childhood nutrition. Girls, as noted, are protected by high estrogen levels. Boys -- even boys in adulthood -- are left to fend for themselves.

Research at the prestigious Al Fin Institute suggests that even simulated breastfeeding -- sucking well developed female breasts that are not lactating -- exerts a strong protective effect on the male brain, at any age.  This was a fortuitous finding, since it is much easier to find non-lactating volunteers.

More research is needed. Here at the Institute we have need of volunteers possessing nice, firm, well-developed breasts, so as to refine our earlier studies. No more males are needed, however, since we filled our quota for males within the first five minutes after announcing the study.

Enjoy a Long Day of Sin By Slowing Circadian Clock

The compound, dubbed 'longdaysin,' "massively slows down the body clock, it turns to 24 hour body clock into a 36 hour one," says Steve Kay, chair of biology at the University of California San Diego and an author on the paper published in this week's edition of the online journal PLoS Biology. _USAToday

Have you ever wished to have more hours in the day? With better modulators of the body's built-in biological clock for daily circadian rhythms, you can! Of course the annoying day-night sun cycle will attempt to disrupt your plans, but if you are serious you can simply move underground away from the sunshine and night sky. Why should you be confined by a 24 hour cycle that is only an evolutionary residue left over from man's early origins? We will be leaving this planet for distant horizons sooner or later. May as well get used to adjusting our body clocks to suit our needs, and stop being chained to a the same cycle that regulated the cave men.

Most organisms show daily rhythms in physiology, behavior, and metabolism, which may be advantageous because they anticipate environmental changes thus optimize energy metabolism. These rhythms are controlled by the circadian clock, which produces cyclic expression of thousands of output genes. More than a dozen components of the circadian clock are called clock genes, and the proteins they encode form a transcription factor network that generates rhythmic gene expression. In this study, we set out to control the function of the circadian clock and to identify new clock proteins by means of chemical tools. We tested the effects on the clock in human cells of around 120,000 uncharacterized compounds. Here we describe identification of a novel compound “longdaysin” that markedly slows the circadian clock both in cultured mammalian cells and in living zebrafish. _PLOS

Robots in Cardiovascular Surgery: Guest Article by Susan White

Robots in Cardiovascular Surgery

They’re man’s inventions modeled on himself, and needless to say, they’ve made great strides in almost every field that uses technology. First introduced in factory production lines where automation held the key to improving productivity and efficiency, today, robots have moved on to doing tasks that require brainwork as well thanks to artificial intelligence. However, it was not until a few decades ago that these mechanical wonders were allowed to be used in the field of surgery. And because cardiac surgery is one of the most complicated medical procedures there is, it was only in the 1990s that robots were built and tested for use in the OR.

The benefits of using robots to perform cardiovascular surgeries are many, not just for the patient but for the surgical team too:

The surgery is minimally invasive – there are smaller cuts and openings which in turn translate into less pain, less scarring and a faster recovery period for the patient. Instead of a surgical cut, a small incision is made and an endoscope provides a magnified view of the surgical area using a video camera, using which surgeons perform the operation.

Robots remove the tendency for human errors by eliminating tremor which could cause surgeons to make mistakes when they are overworked or tired.

They provide easy access to body parts that are hard to get to and they allow surgeons to work from various angles and easily manipulate tissue.

They magnify the surgical area so that tiny body parts can be worked on easily and also provide a three-dimensional view which in turn eases the task of the surgical team.

The smaller instruments make it easy to work with children whose body parts are tiny and more fragile.

Robots allow what is called as motion scaling, a technique which allows surgeons to move their hands a certain distance and have it translated into a much smaller distance at the actual surgical site – it’s virtual reduction of movement and it helps when the surgery requires great precision and accuracy.

The camera is voice-activated so surgeons don’t have to free their hands to turn them to the right angle.

The first robot to find a place in the cardiac surgery room was Computer Motion’s AESOP in 1995. It allowed surgeons to repair and replace narrowing or leaking cardiac valves using tiny incisions. It is also being used for work deep within the heart like closing fistulas between coronary arteries and the cardiac chambers.

The da Vinci system and ZEUS were both introduced in 2000 to perform complete robotic heart surgery; both reduce the recovery time for patients by eliminating the need for surgeons to open up the chest through the sternum, a practice that was followed for open heart surgery. Clinical trials have established the safety of these robots in the OR, and it is safe to say that we can expect more complicated machines to assist surgeons in performing cardiac surgeries in the years to come.

By-line:
This article is contributed by Susan White, who regularly writes on the subject of surgical technician schools. She invites your questions, comments at her email address: susan.white33@gmail.com.

Mouse:Human Chimera One More Step

A Salk Institute research team has successfully engineered a mouse strain with a liver consisting of mostly human liver cells. The scientists then infected the mice with human hepatitis virus, and used the mice to test treatments for Hepatitis infection. Eventually, this strain of mouse will allow scientists to test the reaction of human liver cells to drugs, chemicals, viruses, and toxins without endangering human life.

Bissig says his group's mouse/human chimera improves on a similar model developed several years ago that was genetically engineered to give human liver cells a growth advantage when injected into a mouse liver. Researchers engineered the mouse with a gene that destroyed its own liver cells. This programmed death gave human liver cells an advantage, and when researchers injected human hepatocytes, they were able to take over and repopulate the mouse liver. However, scientists found that the genetically engineered mice tended to die off early, which required injecting human liver cells within the first few weeks after birth--a risky procedure that often resulted in fatal hemorrhaging.

Instead, Bissig and his colleagues, including Inder Verma of the Salk Institute, sought to engineer a mouse chimera in which the introduction of human liver cells could be easily controlled. The group first engineered mice with several genetic mutations, which eliminated production of immune cells so that the mice would not reject human liver cells as foreign. The researchers made another genetic mutation that interfered with the breakdown of the amino acid tyrosine. Normally, tyrosine is involved in building essential proteins. To keep a healthy balance, the liver clears out tyrosine, keeping it from accumulating to toxic levels. Bissig engineered a mutation in mice that prevents tyrosine from breaking down, instead causing tyrosine to build up in liver cells, eventually killing the mouse cells, giving the human cells an advantage.

To avoid killing mouse liver cells too early (or killing the mice entirely), Bissig's team administered a drug that blocks the toxic byproducts of tyrosine buildup from killing liver cells. By putting the mice on the drug, and taking them off the drug a little at a time, researchers found that they could control the rate at which rodent liver cells died off.

The team then injected mice with hepatocytes from various human donors, and found that the cells were able to take over 97 percent of the mouse liver. The "humanized" mice were then infected with hepatitis B and C, and researchers found high levels of the virus in the bloodstream--versus normal mice, which are impervious to the disease and are able to clear the virus out quickly.

Bissig and his colleagues went a step further and treated the infected mice with a drug typically used to treat humans with hepatitis C. They found that, after treatment, the mice exhibited a thousand-fold decrease in viral concentration in the blood, similar to drug reactions in human patients. _TechReview

This team is focused on hepatitis viruses, but clearly the application of this chimeric technology goes light years beyond testing treatments for a virus or two.

Scientific publications must have a narrow focus in order to be taken seriously. But the implications of particular studies may reverberate far beyond the narrow intent of the original study. That is the case here.

Bissig says that in the future, he and his team hope to add a human immune system to their mouse model, so they can see how hepatitis acts, not only in a human liver, but in the presence of a normal, healthy human immune system.

Why stop there? Chimeric technology will allow animal organs to be replaced by human organs, piece by piece, creating perfect animal models for the study of human disease. But why stop there? Scientists are replacing animal brain tissue with human neuronal stem cells that develop into human neurons. Why not give the little critters human brains too? We can do it. We have the technology . . . .

The fact is, the djinn is out of the bottle -- has been out of the bottle since the discoveries of Watson, Crick, and others who preceded them.

The only question is: How far will we take the idea? The answer is that "we" are no longer in control. Biotechnology is a lot easier to teach, transport, and conceal than nuclear weapons technology. And a lot more dangerous, if you want to hear the truth.

Time to wake up to the things we need to be preparing for.

Cancer Screening Achieves Frightening Sensitivity

Yale researchers have devised nano-sensors capable of detecting and measuring minute levels of cancer biomarkers in whole blood. Detection down to the concentration of picograms per milliliter -- with 10% "accuracy" -- are claimed. That is said to be equivalent to detecting a single grain of salt within a large swimming pool.

Their findings, which appear December 13 in the advanced online publication of Nature Nanotechnology, could dramatically simplify the way physicians test for biomarkers of cancer and other diseases.

The team—led by Mark Reed, Yale's Harold Hodgkinson Professor of Engineering & Applied Science, and Tarek Fahmy, an associate professor of biomedical and chemical engineering—used nanowire sensors to detect and measure concentrations of two specific biomarkers: one for prostate cancer and the other for breast cancer.

"Nanosensors have been around for the past decade, but they only worked in controlled, laboratory settings," Reed said. "This is the first time we've been able to use them with whole blood, which is a complicated solution containing proteins and ions and other things that affect detection."

To overcome the challenge of whole blood detection, the researchers developed a novel device that acts as a filter, catching the biomarkers—in this case, antigens specific to prostate and breast cancer—on a chip while washing away the rest of the blood. Creating a buildup of the antigens on the chip allows for detection down to extremely small concentrations, on the order of picograms per milliliter, with 10 percent accuracy. This is the equivalent of being able to detect the concentration of a single grain of salt dissolved in a large swimming pool. _Eurekalert

Now the question is: what do you do with someone when you detect a cancer biomarker at extreme low concentrations? Of course you can do other blood tests, multiple types of scans, xrays, biopsies, etc. to try to confirm and localise the malignancy. But at extreme low levels of biomarker there is a good chance that you will not be able to find any other evidence of disease. Then what?

Then you watch the patient more closely than you would have watched them otherwise. Serial biomarker testing using nano-sensors may prove to be the best way of following such "low-positive" patients. It will take time to incorporate such sensitive tests into clinical practise.

National Health Services may elect not to use such sensitive screening tests at all (or very selectively), due to the likely added expense of monitoring and confirming low-positive tests. Private insurance companies -- if any still exist in a few years -- will have no choice but to use whatever the standard of care is decided to be. Government run programs can do what they want, since a dead patient generates no further expenses ( so long as you cannot sue the government).

Once genetic screening tests are more readily available at the clinic level, along with nano-sensors for cancer, infectious agents, toxins, etc etc, the practise of primary care medicine is likely to change.

HIV and AIDS: A Question of Causation

A recent controversy has sprung up around the decision of the journal Medical Hypothesis to publish a paper by Peter Duesberg, a famous critic of the dominant medical belief that HIV causes AIDS. Several websites are dedicated to refuting the "HIV causes AIDS" hypothesis, including Heal Toronto. Millions of reasonably intelligent people have become highly skeptical of HIV as the cause of AIDS.

The problem goes back to the basic issue of causation -- specifically disease causation. Koch's postulates for establishing microbial disease causation include:

1. Isolate the organism from every case
2. Propagate in pure culture in vitro
3. Reproduce disease by injecting the organism into a suitable recipient
4. Re-isolate the organism
__microbiologybytes

These postulates have served quite well over the years, but for some microbial diseases they have proved insufficiently powerful to establish causation. Variations in microbe virulence and in host susceptibility can complicate the establishment of causation.

A more subtle set of postulates for establishing genetic virulence in  more ambiguous situations, have been dubbed the "Molecular Koch's Hypotheses"

1. Identify gene (or gene product) responsible for virulence determinant
2. Show gene present in strains of bacteria that cause the disease
3. Not present in avirulent strains
4. Disrupting the gene reduces virulence
5. Introduction of cloned gene into avirulent strain confers virulence.
6. The gene is expressed in vivo
7. Specific immune response to gene protects
__microbiologybytes

In the case of HIV / AIDS, the classical Koch's Postulates cannot be tested ethically, since intentionally injecting a human with HIV might easily lead to charges of attempted murder against the researcher.  Of course, not even Duesberg himself is likely to be so reckless as to inject himself or others with HIV intentionally.   Which may be one way of measuring the limits of skepticism for this particular hypothesis.  Is the skeptic willing to inject himself with HIV?

At one time, Peter Duesberg was better known as a leading cell biologist and discoverer of the first true human oncogene, src, in 1970.  A long-time tenured professor at UCB and a member of the NAS, Duesberg's vocal skepticism of the HIV to AIDS hypothesis has, since his 1996 book "Inventing the AIDS Virus", placed him well out of the mainstream of biomedical thought.

It is not the intent of Al Fin Epidemiiologists to refute Duesberg's various lines of arguments in a blog post.  Rather, it is the intent of this posting to take a short peek into the phenomenon of human belief itself.   Duesberg's various lines of attack against the HIV to AIDS theory have been sufficient to establish strong doubts in the minds of large numbers of intelligent thinkers. 

Al Fin Epidemiologists do not accept Duesberg's arguments as convincing, but then Al Fin Epidemiologists are trained to go to root issues when determining the likelihood of an argument -- particularly an argument dealing with disease causation.   For Al Fin Epidemiologists -- unlike most people -- the question is not one of belief.  It is a question of likelihood, and the most likely routes to efficacious disease therapies and cures.  These are things that can be tested -- or falisified -- as Karl Popper would put it.

Humans are prone to "beliefs", which may or may not be well supported by testable facts or observations.  Humans are easily seduced by "reason and rationality" into forsaking empirical testing of apparent "facts".   How much time is wasted in the media, in congress and parliament, in the social sciences, and in dorm rooms and homes -- on arguments that are not formulated to produce testable hypotheses? 

Instead of bullishly "believing" or "disbelieving", humans should always be asking, "How can I test that assertion?"  If assertions, assumptions, and lines of argument do not lend themselves to testing, they are essentially a waste of a practical person's time.

That is how Al Fin Epidemiologists view Duesberg's arguments over the "HIV to AIDS" hypothesis.  Worse than Duesberg's arguments, are the "meta-arguments" that spring up over Duesberg's original arguments.  These meta-arguments then spawn their own "meta-meta-arguments" in a recursive explosion of wasted hours, days, weeks, months, and years.

What can be tested?

If HIV infection leads to low CD4 cell count, and if low CD4 cell count is associated with much higher incidences of PCP pneumonia, Kaposi's sarcoma, CMV, and a host of other low-immunity associated and opportunistic infections and malignancies, these associations lead directly to testable hypotheses.

If a rebound to higher CD4 cell counts after retroviral treatments is associated with remission from opportunistic diseases, further falsifiable hypotheses can be generated.

In fact, the pertinent level of testable argument, scientifically, lies far away from most of Duesberg's arguments.  That is the main problem that Al Fin Epidemiologists have with Duesberg's arguments -- not his skepticism.  Al Fin applauds skepticism wherever it is productive of meaningful falsifiable hypotheses.

Humans in advanced, High IQ societies are not being taught to use their rationality, their judgment, their discriminatory powers of mind.  This leads to lifelong adult-children, incompetent on many fronts, and ineffectual in determining basic probabilities, likelihoods, and wise choices of everyday life.

Human Rationality Has Designs on Itself

Human rationality -- such as it is -- seems to be looping back upon itself. It looks as if the human brain may become the beneficiary of "rational drug design." The methods of rational drug design are advancing by leaps and bounds, so that we should expect some significant benefits quite soon.  Researchers at Tel Aviv University are focusing rational design to create drugs for Alzheimer's, Parkinson's, and Huntington's diseases.

Since Prof. Eldar-Finkelman linked GSK3 to insulin resistance in diabetes more than ten years ago, a race has been on among drug manufacturers to find a drug that can potentially turn off the harmful effects of GSK3. But rather than build on existing drugs, Prof. Eldar-Finkelman and her colleagues worked from the ground up. "I decided to take a completely different approach from all the big drug companies rushing to find the ultimate drug," says Prof. Eldar-Finkelman. "I designed my own."

Pre-clinical results have been positive, and the new drug does not exhibit dangerous toxic side effects, a problem with existing formulations. While L803-MTS cannot reverse the onset of a CNS disease once it has started, Prof. Eldar-Finkelman believes it can slow down the devastating effects of CNS diseases, like impaired memory and depression, or insulin-resistance.

"Ours is the first lab that showed the importance of GSK3 as a target in Type II diabetes, and was among the first to introduce a specific inhibitor against the GSK3," she says. "Our approach became so popular that today many pharmaceutical companies, big and small, are competing to work on a GSK3 inhibitor."

..."One important thing to note is that our drug acts differently than other compounds," she says. "Most GSK3 inhibitors are developed on the basis of ATP competitors. Ours are substrate competitors, meaning that they bind to a different site at the surface of the protein. This strategy is completely different, and yields a better and safer compound."

Prof. Eldar-Finkelman is now conducting additional pharmacological and toxicological tests on the new compound. She believes it will be a lead compound for treating CNS disorders, "because it was based on rational drug design. We started from scratch and thought through the design of a specific compound that would be safe and effective. Our aim is to slow the progression of CNS diseases, but the new drug might also be used as a preventative therapy," she adds. _SD

Rational drug design has come a long way in the past 10 years since Vertex began making waves. Advances in protein simulation, protein imaging, atomic force microscopy, haptics, bioinformatics, and other tools of research are allowing researchers to bypass tedious approaches such as "rapid screening" in order to aim directly at a drug target. Of course it is never really "either-or." In the end, many more tools will be developed, and all of the tools will be used to get us where we wish to be.

Clever $20 Disposable Cartridge Blood Test Quickly Detects Virtually Any Type of Cancer

Raj Krishnan, a graduate bioengineering student at UCSD, has developed an inexpensive electrophoretic device that promises to detect virtually any type of cancer in the body with a quick, cheap, blood test. Such an inexpensive, broad spectrum cancer screen has been the holy grail of preventive medicine and medical screening for decades.

Cancers that are detected early have the best chance of being cured but, until now, there were no methods of detecting cancer at its earliest stages. Raj Krishnan, a PhD student in bioengineering at the University of California San Diego (UCSD), has created a technology for the early diagnosis of cancer, giving new hope and possibility to cures that have eluded cancer victims for years because their diagnoses were too late.

Krishnan focused his study on the DNA that roams cell-free in the blood as cancers develop, trying to figure out how to separate out the nanoparticles of DNA without degrading them. These nanoparticles are between 5 and 50 nanometers in size, smaller than the wavelength of light.

As Krishnan's professor, Michael Heller, noted: “It’s very difficult to find [cell-free DNA] in blood. The analogy of needle in the haystack has been used, but I’d say it’s more like looking for a needle on the whole farm.”

Actually, it was harder than that, because Krishnan was bucking a process -- using electric field techniques -- that other researchers in the field had "proven" would not work. Krishnan was able to find the right circumstances under which the DNA could be isolated in tact with electric field technology, and he demonstrated it!

Even Professor Heller was dubious about the discovery and spent six months, along with Krishnan, trying to figure out why no one else had discovered it. Then, finally convinced, Heller, Krishnan, and fellow grad students David Charlot and Roy Lefkowitz filed the patent applications, and founded a company, Biological Dynamics, to move their diagnostic technology into clinics.

Their product is a cost-effective blood test that takes less than 30 minutes and detects almost every cancer type. Their business plans call for developing two products: a blood analyzing system which will be priced at approximately $20,000 and disposable electrode cartridges to do the tests, priced at about $20. _Investorspot_via_Impactlab

Easy detection of a wide range of cancers will allow for earlier intervention in the curable stage of most cancers. Some cancers will remain incurable, no matter the stage of detection, and other cancers might be best ignored -- such as low grade prostate cancers in elderly men. Optimal screening schedules would depend upon age, sex, and family history.

But a highly accurate $20 blood test is a much cheaper screen than a colonoscopy, mammography, CT scans, nuclear medicine scans, MRI, exploratory surgery, and any number of other methods of screening, or of ruling out malignancy. In the catastrophically expensive atmosphere of "defensive medicine" created in the US by out-of-control trial lawyers, any reliable way of avoiding testing that can easily cost tens of thousands of dollars, would be helpful.

Biotech and Nanotech: Novel Cancer Killers

Until recently, physicians have had to rely on "sledge hammer" treatments for fighting cancer: surgery, radiation, chemotherapy. All three mainstream approaches to cancer therapy can kill the patient, or have devastating effects on the person's quality of life above and beyond any impact from the cancer. Both doctors and patients would like access to finely targeted therapies that kill only the cancer, and leave the patient whole and healthy. Both biotech and nanotech (as well as the two combined) offer hope for such "magic bullet" therapies.

Specialists at the Curie Institute in Paris have devised a method of "baiting" cancer cells into killing themselves, using special DNA decoys.

North Carolina State University researchers are using modified plant viruses coated with targeting molecules to selectively target and destroy cancer cells.

UC Santa Cruz researchers are coating hollow gold nano-spheres with short-chain targeting molecules that bind to cancer cells. Infrared light beamed onto the tumour is trapped by the gold particles, and the cancer cells are cooked.

Tel Aviv University researchers are building nano-submarines out of phospholipids, filling them with siRNA particles that shut down the target cell's cell division machinery, and coat them with specific targeting molecules.

German researchers are injecting nano-magnetic particles of iron directly into tumours, then using an extermal oscillating magnetic field to induce a killing heat inside the cancer.

You can see how the convergence of nanotech and biotech is aiding researchers in their highly specific targeting of tumour cells, and other cells of interest (over-active immune cells in autoimmune disorders). Some of these treatments require the application of external energy (infrared light, magnetic fields, heat, etc), and other approaches insert the killing impetus inside the nanoparticle itself. Most of the methods use bio-targeting molecules to guide the nanoparticle to the cells of interest.

This is only the beginning. As long as the entire economic infrastructure of the western world is not destroyed by the neofascists currently reigning in Washington, resources will continue to find their way to productive researchers. The pace of discovery may slow, as more resources are diverted to non-productive government programs as well as to politically connected crony-friends of the reich. It is quite possible that even after cleaning out the rat's nest through future elections, recovery from the current spree of corrupt dysfunction may take many years, or decades.

Ancient Sponges May Help Humans Survive

Researchers led by Moeller, of Hollings Marine Laboratory in Charleston, found a sponge thriving in the midst of dead organisms. This anomalous life amidst death raised an obvious question, says Moeller: “How is this thing surviving when everything else is dead?”

Chemical analyses of the sponge’s chemical defense factory pointed to a compound called algeferin. Biofilms, communities of bacteria notoriously resistant to antibiotics, dissolved when treated with fragments of the algeferin molecule. And new biofilms did not form. _ScienceNews

Sea sponges live in a very tough neighborhood, microbially speaking. The billion-year arms race between competing organisms, and between predator and prey, has left a long trail of failed survival strategies in its wake. But the strategies that have worked, time and time again, can prove extremely potent.

Humans have their own arms race against bacteria, involving human manufactured antibiotics vs. some very clever strategies developed by bacteria over a billion year span or so. On the front lines of this battle, inside most of the hospitals of the world, bacteria are winning. Humans have been forced to come up with ever more expensive strategies to combat multiply resistant bacteria. What if we could borrow powerful strategies from other, more "street savvy" organisms? More of us might survive longer.

The compound is able to reprogram antibiotic-resistant bacteria that don’t form biofilms. When bacteria are treated with the compound, antibiotics that usually have no effect are once again lethal. This substance may be the first one that can restore bacterial resistance, Moeller says. “This resensitization is brand new.”

And the problem of perpetuating a bacterial-resistance arms race, in which bacteria rapidly develop countermeasures against new antibiotics, may be avoided entirely with the new compound. “Since the substance is nontoxic to the bacterium, it’s not throwing up any red flags,” says Moeller.

...The research is still in very early phases.

“Everyone would like to see this in antibiotic trials tomorrow,” Moeller says, but treatments for human infections are a long way off.

Sotka agrees. “Of course, we need clinical trials to take it to the next level,” she says. _ScienceNews

Scientists are sending out "scouts" to all the continents, oceans, seas, lakes, large islands, mountain peaks, and polar extremes of the world to find the winners of the ancient arms race between microbes, and between microbes and multi-cellular organisms. Improved mass screening technologies allow rapid throughput analyses of these organsims and their strategies, so that we can select the best in their class, for our purposes.

Under the Obama / Pelosi reich, the rich biomedical research community is likely to be starved for funds to conduct such research, since the new reich plans on diverting most of America's wealth -- including private sector wealth -- into government run human and social services.

Even so, the current momentum of research in university science labs, corporate labs, and other labs performing actual science, will persist for some years to come. It will take time for the reich's changed priorities to take over all the research funding agencies. Everything hinges upon the American voter, and whether they will wake up in time.

Another Revolution in Pharmacology

Research into the effects of melanocortins is incredibly exciting in its potential to revolutionise medicine. Here are a few of the effects of melanocortin peptides on the brain:

Induction of spontaneous penile erections
Increase of [sexual] proceptivity and receptivity (in females)
Increase of motivation
Increase of attention
Improvement of short-term memory
Increase of visual retention
Lowering of auditory, gustatory and olfactory detection thresholds
Functional antagonism of opiate effects
Inhibition of feeding (satiety-inducing effect)
Antiinflammatory effect (sites of action: brain and immunocytes)
Antipyretic effect
Reversal of hypovolemic hypotension
Reversal of shock
Resuscitation after prolonged asphyxia
Improvement of recovery after traumatic brain lesions and spinal cord injuries
Delay of the aging-linked behavioural deficits
Beneficial influences in neurodegenerative disorders
Increase of regenerative capacity of peripheral nerves in postlesion repair
Improvement of diabetic and toxic neuropathies
_Pharmacological Research

Like I say, those are a few of the effects that have been discovered so far for the melanocortins (melanocyte stimulating hormones [MSH], ACTH). New drugs which can either block or stimulate these hormone receptors will likely revolutionise treatment for:

1. Alzheimer's and other neurodegenerative disease
2. Stroke
   
3. Diabetic Neuropathy
4. Hemorrhagic Shock
5. Sexual Dysfunction for males and females
   
6. Obesity
7. Anorexia and Cachexia
8. Depression
9. Anxiety
10. Various learning disorders

...and quite a few things more. It is only in the past decades that scientists have been able to distinguish different receptor types for the many peptides and neurotransmitters affecting the brain and nerves. Now, it looks like nothing can stop the steamroller of biomedical and biotech research -- except perhaps bad government that wastes precious resources on policies that have failed for many generations.

If you have an interest in any of the listed diseases or hormonal effects above, visit the linked article and skip down to the section that interests you particularly. It is a long review article that covers a wide range of effects and potential therapies. I strongly recommend learning to read scientific articles -- despite their dryness -- because any person who can draw meaning from the early stages of research can often see into the future, and profit from that vision. If you wait until "science journalists" spell it out and dumb it down for you, it may be too late.

When the baby revolutions of nanotechnology, biotechnology, information sciences, and cognitive sciences begin to grow up and converge, you will begin to understand how quickly things can change.

Synthetic HDL Cholesterol Sponge: Nanotechnology Making Cholesterol Safer

The nano-synthesis of biologically active molecules has a huge future in biomedicine. One example of such a synthetic biomolecule is synthetic HDL cholesterol, recently synthesised by Northwestern University scientists.

The researchers successfully designed synthetic HDL and show that their nanotechnology version is capable of irreversibly binding cholesterol. The synthetic HDL, based on gold nanoparticles, is similar in size to HDL and mimics HDL’s general surface composition. The study is published online by the Journal of the American Chemical Society (JACS).

“We have designed and built a cholesterol sponge. The synthetic HDL features the basics of what a great cholesterol drug should be,” said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, professor of medicine and professor of materials science and engineering. Mirkin and Shad Thaxton, M.D., assistant professor of urology in Northwestern’s Feinberg School of Medicine, led the study. _Nanowerk

A previous use of synthetic HDL cholesterol is as a tracer molecule, to identify atherosclerotic plaque inside arterial lining. Tagging the synthetic HDL with likely MRI contrast agents such as gadolinium allowed for the rapid location and size estimate of cholesterol plaques.

"It's like a smart bomb that goes directly to the plaque," says Fayad. "We were able to see plaque in high contrast."

In their images, the team also detected accumulations of macrophages--killer cells that invade areas of injury or inflammation such as plaque buildup. These macrophages secrete enzymes that Fayad says "eat up" plaque, making it unstable and more likely to rupture, which in turn could lead to heart attacks. Being able to detect these cells early on could help identify people at high risk of heart disease, as well as help develop treatments and lifestyle changes before their condition worsens. _Medgadget

More on using nano-synthetic HDL to aid in diagnostic testing for atherosclerosis here.

Return to Mitochondria

Mitochondria are the powerhouses of the cell. If the mitochondria are not healthy, the cell will not be healthy. Drug researchers are beginning to make the connection between drug candidates and mitochondrial health. This dawning awareness should lead to some startling developments in treatments for degenerative diseases such as diabetes--perhaps even for chronic fatigue syndrome. Researchers should also now be able to better avoid new drugs that cause side effects due to induced mitochondrial dysfunction.

Mootha and his team zeroed in on five basic features of mitochondria activity, looking at how a library of 2,500 chemical compounds affected mitochondrial toxic byproducts (like all “chemical factories” mitochondria produce their own toxic waste), energy levels, speed with which substances pass through these organelles, membrane voltage, and expression of key mitochondrial and nuclear genes. (Mitochondria contain their own genome, consisting of approximately 37 genes in humans.)

“It’s just like taking your car in for an engine diagnostic,” explains Mootha. “The mechanic will probe the battery, the exhaust system, the fan belt, etc., and as a result will then produce a read-out for the entire system. That’s analogous to what we’ve done.”

As a result of these investigations, Mootha and his group produced three major findings.

First, the team discovered a pathway by which the mitochondria and the cell’s nuclear genome communicate with each other. They found this by discovering that certain drugs actually broke communication between these two genomes. By reverse engineering the drugs’ toxic effects, they may be able to reconstruct normal function.

Second, the team looked at a class of the cholesterol-lowering drugs called statins. Roughly 100 million Americans take statins, and among that group, about 1 million experience muscle cramping and aches. Previous studies suggested that mitochondria were involved, but clinical evidence remained conflicting. Mootha and his colleagues found that three out of the six statins (Fluvastatin, Lovastatin, and Simvastatin) interfered with mitochondria energy levels, as did the blood-pressure drug Propranolol. When combined, the effect was worse.

“It’s likely that a fair number of patients with heart disease are on one of these three statins as well as Propranolol,” says Mootha, “Our cellular studies predict that these patients might be at a higher risk for developing the muscle cramps. Obviously, this is only a hypothesis, but now this is easily testable.”

The third and arguably most clinically relevant finding builds on a paper Mootha coauthored in 2003, a paper that demonstrated how type 2 diabetes was linked to a decrease in the expression of mitochondrial genes. A subsequent and unrelated paper showed a relationship between type 2 diabetes and an increase in mitochondrial toxic byproducts. Mootha’s group decided to query their toolkit and see if there were any drugs that affected both of these functions, drugs that could boost gene expression while reducing mitochondrial waste.

Indeed, they found six compounds that did just that, five of which were known to perturb the cell’s cytoskeleton, that is, the scaffolding that gives a cell its structure.

“Our data shows that when we disrupt the cytoskeleton of the cell, that sends a message to boost the mitochondria, turning on gene expression and dropping the toxic byproducts,” says Mootha. “The connection between the cytoskeleton and mitochondrial gene expression has never been shown before and could be very important to basic cell biology.”

Of the five drugs that did this, one, called Deoxysappanone, is found in green tea and is known to have anti-diabetic effects. Another, called Mebendazole, is used for treating intestinal worm infections. This connection gives a rationale to case reports in which diabetics treated with Mebendazole have described improvements in their glucose levels while on the drug.

The researchers intend to further investigate some of the basic biological questions that this study has raised, foremost being the relationship between the cytoskeleton and mitochondria. They also plan on using this toolkit to develop strategies for restoring normal mitochondrial function in certain metabolic and neurodegenerative conditions where it has broken down.

Nature Biotechnology, February 24, early online edition___Newswise

The connection between mitochondrial health and many other common degenerative diseases--besides diabetes--is there, waiting to be sorted out. Effective treatment for mitochondrial dysfunction is apt to be most widely applicable to a wide range of diseases which were formerly believed to be unrelated to each other.

Non-invasive Brain Oximeter--Let There Be Light

Neurosurgical intensive care units and emergency rooms have long needed a quick, non-invasive way of measuring the state of the brain. CT scans and MRI's are expensive, time-consuming, and cannot be kept at the bedside. A new type of brain oximeter takes advantage an interesting pheonmenon--ultrasonic light tagging.

Information on oxygenation in specific regions of the brain would be valuable to neurologists monitoring a brain-injured patient, as it could be used to search for localized hematomas and give immediate notice of hemorrhagic strokes. When a stroke occurs, an area of the brain is deprived of blood and thus oxygen, but there is no immediate way to detect the attack's occurrence.

CT and MRI scans give a snapshot of tissue damage, but they can't be used for continuous monitoring. It can also be very difficult to conduct such scans on unconscious patients hooked up to life-support devices.

....OrNim's new device uses a technique called ultrasonic light tagging to isolate and monitor an area of tissue the size of a sugar cube located between 1 and 2.5 centimeters under the skin. The probe, which rests on the scalp, contains three laser light sources of different wavelengths, a light detector, and an ultrasonic emitter.

The laser light diffuses through the skull and illuminates the tissue underneath it. The ultrasonic emitter sends highly directional pulses into the tissue. The pulses change the optical properties of the tissue in such a way that they modulate the laser light traveling through the tissue. In effect, the ultrasonic pulses "tag" a specific portion of tissue to be observed by the detector. Since the speed of the ultrasonic pulses is known, a specific depth can be selected for monitoring.

The modulated laser light is picked up by the detector and used to calculate the tissue's color. Since color is directly related to blood oxygen saturation (for example, arterial blood is bright red, while venous blood is dark red), it can be used to deduce the tissue's oxygen saturation. The measurement is absolute rather than relative, because color is an indicator of the spectral absorption of hemoglobin and is unaffected by the scalp.

Deeper areas could be illuminated with stronger laser beams, but light intensity has to be kept at levels that will not injure the skin. Given the technology's current practical depth of 2.5 centimeters, it is best suited for monitoring the upper layers of the brain. Smith suggests that the technology could be used to monitor specific clusters of blood vessels.

While the technology is designed to monitor a specific area, it could also be used to monitor an entire hemisphere of the brain. Measuring any area within the brain could yield better information about whole-brain oxygen saturation than a pulse oximeter elsewhere on the body would. Hilton Kaplan, a researcher at the University of Southern California's Medical Device Development Facility, says, "If this technology allows us to actually measure deep inside, then that's a big improvement over the limitations of decades of cutaneous versions."

Michal Balberg, the CEO and cofounder of OrNim, thinks that it may ultimately be feasible to deploy arrays of probes on the head to get a topographic map of brain oxygenation. In time, brain oxygenation may be considered a critical parameter that should be monitored routinely.

Technology Review

One more step to Dr. McCoy's scanner wand.

New Alzheimer's Treatment Approach

An excess of Beta amyloid protein in Alzheimer's patients leads to amyloid plaques and eventual neuronal death. One new approach to treating Alzheimer's is to block the enzymes that cleave the longer protein "APP" into Amyloid Beta, or A Beta.

The molecule, called a beta-secretase inhibitor, prevents the first step in a chain of events that leads to amyloid plaque formation in the brain. This plaque formation creates fibrous clumps of toxic proteins that are believed to cause the devastating symptoms of Alzheimer's.

The study of 48 healthy volunteers showed dose-related reduction in plasma amyloid beta, a protein believed to be a key biomarker of Alzheimer's. Results showed a single dose of the drug produced a greater than 60 percent reduction of the biomarker. Subjects received one of six different doses or a placebo, and the study measured levels of the therapeutic drug and levels of the biomarker in the bloodstream.

"The phase I clinical results are very exciting," Ghosh said. "We hope that this beta-secretase inhibitor drug will be one of the first disease modifying treatments that stops or reverses the symptoms of Alzheimer's disease."

Science Daily

Several new approaches to Alzheimer's treatment are aimed at the A Beta protein--either in preventing its overproduction, or in speeding its elimination. Here is an interesting approach--a vaccine against Amyloid Beta. These approaches have the potential to prevent the onset or full manifestation of Alzheimer's, once diagnosed or strongly suspected. Better screening tests and genetic tests should allow good selection of candidates for various primary and secondary preventive strategies.


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