Leading ovarian cancer researchers and clinicians from around the world will meet in Seattle September 4-5 to discuss exciting new discoveries and recent scientific findings to fight ovarian cancer, which kills more than 15,000 women every year. The news media will get a sneak peek at these discoveries during a morning news conference on September 4.

“Early detection of ovarian cancer is one of the most critical factors to improving the prognosis for women diagnosed with this disease,” said Nancy Sclater, Executive Director of the Marsha Rivkin Center for Ovarian Cancer Research. “This symposium will reveal advances being made in early detection which will be critical while we search for a cure.”

The two-day symposium will be held at the Pigott Auditorium on the campus of Seattle University and marks the beginning of Ovarian Cancer Awareness Month. More than 50 researchers will share their findings including the fact that ovarian cancer may not even start in the ovaries, new research to use urine tests for early detection, and new strategies for improving drug penetration for patients diagnosed with ovarian cancer.

The symposium will also feature four keynote addresses from some of the brightest names in ovarian cancer research. On Thursday, Christopher Crum, MD, from Harvard Medical School, will discuss the origins of ovarian cancer, and Anil K. Sood, MD, from University of Texas, MD Anderson Cancer Center, will present on the development of therapeutics.

Friday’s keynote presentations will feature Maurie Markman, MD, also from University of Texas, MD Anderson Cancer Center, who will present his research on therapeutics. The last keynote address will cover research on inherited ovarian cancer, presented by local and well-renowned researcher Mary-Claire King, PhD, from the University of Washington.

A news conference with the keynote speakers, Sclater and Dr. Saul Rivkin is scheduled to kick-off the symposium at 9:30 a.m. on Thursday, Sept. 4. Details are below.

The Marsha Rivkin Center for Ovarian Cancer Research was founded in 1996 by Saul Rivkin, M.D., in memory of his wife who succumbed to ovarian cancer. It has been the catalyst for national and international research efforts aimed at finding solutions to ovarian cancer. The Center is dedicated to saving lives and reducing suffering through improved treatment, early detection and prevention of ovarian cancer.

Marsha Rivkin Center for Ovarian Cancer Research Continue reading →

Tooth cavities are usually closed with plastic fillings. However, the initially soft plastic shrinks as it hardens. The tension can cause gaps to appear between the tooth and the filling, encouraging more caries to form. For the first time, researchers have simulated this process.

The patient’s hands are clasped firmly around the armrests as the dentist drills away the caries-stricken sections of the tooth. Once the drilling is over, most toothache sufferers can begin to relax. All the doctor now has to do is to slightly etch the cavity, apply an adhesive film, and fill it with a special type of plastic. The plastic is soft at first, so that the doctor can easily press it into the cavity. It only solidifies afterwards under the light of a small lamp. However, the material tends to shrink slightly as it hardens, occasionally producing tension that can cause tiny gaps to form between the plastic filling and the tooth. Bits of food can get caught in these gaps and lead to more caries. Manufacturers of filling materials therefore offer a variety of plastics to choose from. But which filling is best suited to which shape of cavity? This is where dentists have to draw on their experience. “Until now, it has not been possible to establish a theoretical model of the hardening process. The tension occurring in the material always depends on the shape of the cavity, and can vary widely by a factor of up to ten, particularly at the edges,” says Dr.-Ing. Christof Koplin, research assistant at the Fraunhofer Institute for Mechanics of Materials IWM in Freiburg. Measurements do not help either, as tension can only be measured selectively. Its precise course of development has never yet been observed.

A new method of simulation now enables tension in dental fillings to be accurately predicted, helping doctors to choose the least tension-prone plastic for each shape of cavity. Dentists can now draw on the results of the IWM to select the best material, and manufacturers can use the simulations to optimize their products. “We theoretically subdivide the dental filling into thousands of small parcels and calculate how each element affects its neighbor. Experimental parameters are incorporated in the individual elements. We started our laboratory tests by using a standard geometry to find out how each material reacts to the stresses that occur when the volume shrinks, and how the flow capability of the material changes as it hardens,” explains Koplin. The IWM researchers have now successfully simulated the development of tension in dental fillings for various cavity shapes and materials, and more will follow.

Fraunhofer-Gesellschaft
fraunhofer.de Continue reading →

Spherix Incorporated
(Nasdaq: SPEX) has successfully completed its dose range-finding study,
allowing it to continue with its Phase 3 clinical trial of Naturlose as a
treatment for type 2 diabetes (see Spherix news releases dated May 23,
2006, and August 10, 2006). The tests were done on human subjects to
establish the appropriate dosage and timing to be used in the upcoming
trial. The Company will now recruit patients for the trial, which will take
place in Australia and the United States. Company officials expect that the
first participants will begin the Phase 3 clinical trial by April 2007.

“The test results so far have been positive,” said Spherix President
Richard Levin. “Not only did they determine the dose and timing for the
trial, but the results corroborate what we have seen in smaller, previous
tests — that Naturlose has a beneficial effect on modulating postprandial
blood glucose, an important factor in the treatment of Type 2 diabetes. We
are moving forward with confidence that we have a scientifically sound
foundation on which to complete the Phase 3 trial, and to anticipate a
favorable outcome.”

Levin said that the Company’s recently announced settlement of a
contract dispute (see Spherix’s PR released earlier today) in its
reservations business will bolster its financial ability to support
Naturlose. In that settlement, Spherix agreed to accept $6 million to end
the longstanding legal dispute over the award of the National Recreation
Reservation Service contract. Spherix intends to use a portion of that
payment to support its efforts to develop Naturlose as a marketable
product. Spherix believes these funds, along with existing cash, will
ensure its ability to complete the Phase 3 clinical trial.

If the Phase 3 trial establishes that Naturlose is an effective
treatment for diabetes, Spherix will prepare a New Drug Application (NDA)
for presentation to the Food and Drug Administration (FDA). FDA approval
would give Spherix the right to market Naturlose as a diabetes drug.
Naturlose has already been shown to be safe.

Certain statements contained herein are “forward looking” statements as
defined in the Private Securities Litigation Reform Act of 1995. Because
such statements include risks and uncertainties, actual results may differ
materially from those expressed or implied. Factors that could cause actual
results to differ materially from those expressed or implied include, but
are not limited to, those discussed in filings by the Company with the
Securities and Exchange Commission, including the filing on Form 8-K made
on March 3, 1999.

Under its motto, “A World of Solutions,” Spherix’s mission is to create
value and increase shareholder wealth through innovations that benefit our
clients and the human condition. Spherix offers innovations in information
technology, knowledge management, and biotechnology.

Spherix Incorporated

spherix/ Continue reading →

NephroGenex, Inc., a privately held drug development company focusing on kidney disease, announced the completion of patient enrollment in its Phase 2b clinical trial (PYR-210) studying the safety and efficacy of its lead drug candidate Pyridorin(TM) (pyridoxamine dihydrochloride) in type 2 diabetic patients with overt diabetic nephropathy. Three hundred and seventeen (317) patients have been randomized.

The study is being conducted by the Collaborative Study Group (CSG) at approximately 65 sites in the United States, Australia and Israel. The CSG is a site management organization of nephrologists that has conducted notable landmark studies in diabetic nephropathy in the past, including studies leading to approval of drugs for this indication.

The trial is evaluating two doses of Pyridorin(TM) against placebo in approximately 300 patients for a one year treatment period. Recruited type 2 diabetic patients have elevated serum creatinine levels and significant proteinuria. The estimated study completion date is August 2010.

In previous Phase 2a trials, Pyridorin(TM) therapy demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy as measured by the change in serum creatinine and serum cystatin C over six months, as well as a reduction in urine TGF-beta.

Diabetic kidney disease afflicts about 20% of all diabetics and is the major cause of end-stage renal disease (ESRD) which is an enormous drain on healthcare expenditures. Mortality rates of ESRD patients can reach 20% annually. Pyridorin(TM) has been awarded Fast Track status by the FDA due to the unmet medical need of this life-threatening disease.

About NephroGenex, Inc.

NephroGenex is a drug development company focusing on kidney disease. More than 20 million Americans have some form of chronic kidney disease, and over 400,000 in the US have end stage renal disease requiring dialysis, making renal disease one of the costliest illnesses to treat. The Company is developing Pyridorin(TM) (pyridoxamine dihydrochloride) as a treatment to slow the progression of diabetic kidney disease. Pyridorin(TM) has demonstrated a significant treatment effect in slowing the progression of diabetic nephropathy in two Phase IIa clinical trials, and has been awarded Fast Track status by the FDA. Pyridorin(TM) is one of only a few drug candidates in advanced clinical trials for diabetic kidney disease, and possesses a distinctly new mechanism of action over currently approved treatments. NephroGenex will seek a partner for Phase III development and commercialization.

Continue reading →

The American Society for Therapeutic Radiology and Oncology has updated its brochures Radiation Therapy for Bladder Cancer and Radiation Therapy for Skin Cancer to include the most up-to-date information for patients who are deciding whether radiation therapy is the best treatment option for them.

Both brochures include more detailed information about the different types of treatment available for these cancers and, more specifically, the different types of radiation therapy available. Since cancer treatments can be taxing on the body, new sections were added to inform patients on how to best care for themselves while receiving treatment. Patients will be able to use these brochures to educate themselves on radiation therapy before discussing it as a treatment option with their doctor.

“Deciding on a course of treatment can be a confusing and trying time for a cancer patient,” said Greg Patton, M.D., chair of ASTRO’s Communications Committee and a radiation oncologist at the Rose Quarter Cancer Center in Portland, Ore. “The more patients educates themselves, the more they will be able to understand the different options that their doctor is presenting to them. These brochures are an excellent resource for skin and bladder cancer patients who are looking for more information on radiation therapy.”

According to the American Cancer Society, over 67,000 new cases of bladder cancer, 1 million new cases of basal and squamous cell skin cancers, and 59,000 new cases of melanoma were diagnosed in 2007.

ASTRO is the largest radiation oncology society in the world, with 9,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy.

American Society for Therapeutic Radiology and Oncology Continue reading →

In response to a report published in JAMA, which found that a programme of exercise is beneficial for heart failure patients, British Heart Foundation cardiac nurse Ellen Mason said:

“This controlled trial backs up previous evidence that people with heart failure benefit from a prescribed programme of exercise, by showing they are less likely to die or be admitted to hospital.

“This should reassure people recently diagnosed with heart failure that it is safe to be put into an exercise programme by their doctor.

“Despite the fact that exercise is so obviously beneficial for heart failure patients, they are hardly ever given access to cardiac rehabilitation services, which offer exercise programmes designed specifically for heart patients. The NHS must invest more in cardiac rehabilitation, in line with the overwhelming evidence that it saves lives.”

The British Heart Foundation (BHF) is the nation’s heart charity, dedicated to saving lives through pioneering research, patient care, campaigning for change and by providing vital information. But we urgently need help. We rely on donations of time and money to continue our life-saving work. Because together we can beat heart disease.

Source
British Heart Foundation Continue reading →

The progression of the artery-clogging disease atherosclerosis is linked to the inability of specialized bone marrow cells to continuously repair damage to the arterial lining, Duke University Medical Center researchers have demonstrated.

The researchers also identified characteristic clusters of genes expressed at distinct phases of disease progression. The Duke cardiologists and geneticists believe that the findings of their latest experiments represent a new paradigm for understanding and potentially treating atherosclerosis. They said their finding represents the first time the progression of any chronic disease has been linked to a deficiency in the body’s repair machinery.

Atherosclerosis is marked by the thickening and clogging of blood vessels, which over time can deprive the heart of necessary oxygen and nutrients. While risk factors such as poor diet, smoking, high cholesterol levels and inactivity are important in developing atherosclerosis, the researchers now believe that heredity plays a crucial role in how the body responds to these environmental factors.

“These results provide us with an intriguing new understanding of the disease process involved in atherosclerosis,” said Duke cardiologist Pascal Goldschmidt, M.D., senior member of the research team and chairman of Duke’s Department of Medicine. The results of the Duke studies were published early on-line and will appear in the Nov. 15, 2005, issue of the Proceedings of the National Academy of Sciences. The study was supported by the National Institutes of Health.

“It appears that the disease progresses as the body’s intrinsic ability to repair and rejuvenate itself somehow becomes deficient,” Goldschmidt continued. “It is exciting for us think that if we as physicians could somehow stimulate or maintain a successful repair process in heart patients, we might be able to prevent the development of atherosclerosis even if we can’t completely control other risk factors, such as high lipid levels or hypertension.”

The disease process usually begins with an immune system response to an insult or injury to the arterial lining, said Goldschmidt. Once there, these cells recruit lipids and other fatty materials to the damage site, essentially creating a scar. Over time, the affected arterial cells themselves change, creating a narrower and less elastic artery.

The Duke team focused on the role of a specialized bone marrow cells known as vascular progenitor cells (VPC). These cells circulate throughout the blood stream, respond to the initial damage to the arterial lining and initiate the repair process.

“In our latest experiments, we have demonstrated the natural molecular history of atherosclerosis based on the expression of distinct gene clusters and how changes in VPCs are associated with the progression of disease,” said Duke cardiologist David Seo, M.D., senior author of the paper. “This is the first time the progression of a chronic disease has been linked to changes in the body’s ability to repair itself.”

For their experiments, the researchers used a well-studied strain of mice whose responses to arterial damage closely parallel that of humans. They fed the mice high-fat diets at different ages. Based on the level of disease found in the aortas of mice, they classified the mice as having no disease, early disease, intermediate disease and moderate disease.

The researchers then performed a DNA microarray, or gene chip, analysis of the activity of genes in aorta samples from each of the four groups. Using this novel technique, researchers can quickly screen more than 12,500 known genes, searching for those that are “turned on,” or expressing themselves.

“We found distinct gene clusters, or what we call metagenes, that were activated in each group,” said Ravi Karra, M.D., first author of paper and member of the Duke team as a medical student. He is now conducting residency training at Brigham & Women’s Hospital, Boston. “We know that there won’t be one ‘big bang’ gene involved in a process such as atherosclerosis. These metagenes are like fingerprints, which are specific and unique.”

Specifically, the researchers found characteristic activity in 197 genes associated with the transition from no disease to early disease; 146 genes associated with transition from early to intermediate disease; 110 genes associated with the transition from intermediate to moderate disease; and 650 genes associated with the transition from no disease to moderate disease.

Interestingly, they said, the bulk of the genes expressed in the initiation of disease were found to play a role in lipid and lipoprotein metabolism. These genes are known to influence the metabolism of the arterial wall by controlling the passage of cholesterol. Genes over-expressed in the transition from early to intermediate disease group tended to fall in the area of the immune response and inflammation. For the transition from intermediate to moderate, genes that actually control the remodeling of arterial wall were over-expressed.

With the knowledge of which genes were over-expressed at each stage of disease, the researchers then compared the findings in mice to that of humans and found the results to be strikingly similar.

“The genes we have identified may represent important modifiers of susceptibility and resistance to atherosclerosis,” Goldschmidt said. “These findings could have clinical implications in that the identified genes may represent new targets for intervention. Additionally, the distinct patterns of gene expression may help us determine how advanced the disease may be in patients.”

In past experiments, the Duke researchers demonstrated that injecting VPCs into mice with damaged arteries could repair that damage. Furthermore, they discovered that older VPCs had a less robust repair capacity than younger VPCs.

Armed with this new chronology of genetic expression, or time-line, of the key events in the natural progression of atherosclerosis, the researchers then examined how this information correlated with the age and capability of VPCs.

“Significantly, we discovered that the point in time in the disease where the expression patterns in the aorta begins to change from young VPC to old VPC treatment coincides with the point at which the inflammatory response becomes most noticeable and lesions on the artery start becoming visible,” Goldschmidt explained.

“What surprised us the most was to find out that what seemed from the outside to be a very complex disease may not be that complicated after all,” Goldschmidt continued. “It turns out to be a series of events that make a lot of sense. The key is the body’s reaction to tissue injury, which appears to be governed by certain sets of genes.”

He said that most people can cite an example of someone in their 80s or 90s who smoke or eat unhealthy diets but who are remarkably free of cardiovascular disease.

“Their genetic make-up must give them an amazing capacity for repair,” he said. “But it works the other way as well. Take for example the Olympic skater Sergei Grinkov. He was an incredible athlete with none of the known cardiovascular risk factors, yet he died of a massive heart attack at the age of 28. He probably had a dreadful inherent capacity for repair.”

The Duke cardiologists worked in close collaboration with colleagues from Duke’s Institute for Genome Sciences & Policy and the Center for Human Genetics. Other members of the team, from Duke, were Sreekanth Vemullapalli, Chunming Dong, M.D., Joseph Nevins, Ph.D., and Mike West, Ph.D. Edward Herderick, Ohio State University, was also a member of the team.

Richard Merritt
Merri006mc.duke
Duke University Medical Center
dukemednews Continue reading →

TAAD causes thousands of deaths in the United States each year. Although timely surgical repair of aneurysms can prevent death, thoracic aneurysms are often asymptomatic until dissection (tearing of the vessel wall), and there are few recognized risk factors that can be used for screening. “Prospective identification of patients at risk for TAAD using a genetic strategy will be critical to prevent sudden deaths from this treatable disease,” explains senior study author Dr. John W. Belmont from Baylor College of Medicine.

To begin to unravel the genetic origins of TAAD, lead author Dr. Siddharth Prakash and colleagues at Baylor and Dr. Dianna Milewicz and colleagues at the University of Texas Health Science Center in Houston performed a genome-wide analysis of hundreds of sporadic TAAD cases. The researchers identified 47 copy-number variant (CNV) regions in the TAAD samples when compared with control samples. A CNV is an excess or absence in copies of a particular gene. Previous research has demonstrated that CNVs are linked with many different human diseases.

Specifically, Dr. Prakash and colleagues found that genes within the TAAD CNVs regulate the ability of smooth muscle to firmly adhere within the vessel walls and to contract as the aorta expands and recoils. Importantly, the mutations were linked with molecules whose disruption has been shown to cause inherited TAAD. “Our observations provide strong support for the involvement of multiple rare CNVs that disrupt smooth muscle adhesion or contraction and contribute to both sporadic and familial TAAD. In addition, our findings have implications for other adult-onset cardiovascular disorders,” concludes Dr. Belmont.

Notes:

The primary author for this research is John W. Belmont, Baylor College of Medicine

The first author for this research is Siddharth K. Prakash, Baylor College of Medicine

Continue reading →

US scientists reviewing 20 years of research and expert opinion on generic versus brand name drugs in the treatment of cardiovascular diseases
found no clinical evidence showing brand names were superior to generic versions even though a substantial number of experts writing editorials
advised against interchanging them.

The study was the work of Dr Aaron S Kesselheim, of Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, and
colleagues, and is published online in the 3rd December issue of the Journal of the American Medical Association, JAMA.

When two drugs are bioequivalent it means that to all intents and purposes after they have been given to the patient they are biologically equivalent to
each other, for example the composition, rate and extent to which their active ingredients are present at the target site inside the body are so similar that
you can’t tell the difference between them.

And yet there appears to be a general opinion among doctors and patients that despite the fact generic drugs are bioequivalent to brand name drugs, the
brand names are clinically superior. But generic drugs are much cheaper, so Kesselheim and colleagues decided to investigate the available clinical
evidence on generics versus brand names and the views of editorial writers on the subject with respect to cardiovascular treatments.

For the study, the researchers systematically searched for peer reviewed studies published between 1984 and 2008 and listed in a number of well
known databases, including MEDLINE, EMBASE, and International Pharmaceutical Abstracts.

They selected those studies that compared the clinical effectiveness and safety of generic versus brand name cardiovascular drugs. In a separate
exercise they also identified editorials that wrote about substituting brand names with generic versions.

Kesselheim and colleagues then used techniques commonly used in research that reviews other studies, whereby the design, setting, participants,
results and funding of each study is extracted and put through a test that assesses the quality of the trial, whilst the results are pooled in such a way that
they can then be viewed as if they had come from one giant trial (meta-analysis).

As a separate exercise they reviewed the editorials and classified them as negative, positive or neutral, depending on the authors’ view on generic
substitution.

They found a total of 47 clinical trials covering 9 subclasses of cardiovascular drugs, and established the following results:

38 of the 47 (81 per cent) trials were randomized controlled trials (considered to be higher quality).
For beta-blockers, 7 out of 7 randomized controlled trials (100 per cent) found generics to be clinically equivalent to brand names.
For diuretics, the figure was 10 out of 11 (91 per cent).
For calcium channel blockers it was 5 out of 7 (71 per cent).
For antiplatelet agents it was 3 of 3 (100 per cent).
For statins it was 2 out of 2 (100 per cent).
For angiotensin-converting enzyme inhibitors it was 1 out of 1 (100 per cent).
And for alpha-blockers, 1 out 1 randomized controlled trial (100 per cent) found generics to be clinically equivalent to brand names.
In drugs that have a narrow therapeutic index (where you have to be really careful to give the right dose so as not to injure the patient), clinical
equivalence was found in 1 out of 1 randomized controlled trial (100 per cent) for class 1 antiarrhythmic agents, and in 5 out of 5 (100 per cent) for
warfarin.
Pooling the results of all the trials gave a total of 837 participants and an aggregate effect size of -0.03 (95 per cent confidence interval of -0.15
to 0.08), meaning that across the studies as a whole, there was no statistically significant evidence that brand names were superior to generic drugs.

Reviewing the material from 43 editorials, the researchers found that:

23 of them (53 per cent), expressed a negative view about whether generic drugs could replace or be used instead of brand
names.
This compared with 12 (28 per cent) that encouraged substitution.
The other 8 editorials did not reach a conclusion on interchangeability.
Among editorials covering narrow therapeutic index drugs, 12 (67 per cent) expressed a negative view compared with 4 (22 per cent) in favour
generic substitution.

Kesselheim and colleagues concluded that:

“Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial
number of editorials counsel against the interchangeability of generic drugs.”

They wrote that the rising cost of prescription drugs is a critical policy issue: it strains the budgets of patients and insurance providers, and leads to
poorer health as it works against helping everyone to make sure patients can complete their medication schedules.

“The primary drivers of elevated drug costs are brand-name drugs, which are sold at high prices during a period of patent protection and market
exclusivity after approval by the Food and Drug Administration (FDA),” they added.

The idea of generics is to help people afford drugs, and these become available after the brand names have had their period of being the only ones on
the market, the so called exclusivity period. Many doctors and payers encourage this.

However, some patients and doctors have been concerned that the generic versions may not be as effective. As Kesselheim and colleagues
explained:

“Brand-name manufacturers have suggested that generic drugs may be less effective and safe than their brand-name counterparts. Anecdotes have
appeared in the lay press raising doubts about the efficacy and safety of certain generic drugs.”

Kesselheim and colleagues suggested that one explanation for the discordance between the clinical evidence and the opinion expressed by experts in
the editorials could be that:

“Commentaries may be more likely to highlight physicians’ concerns based on anecdotal experience or other nonclinical trial settings.”

Another explanation they suggested was that the:

“Conclusions may be skewed by financial relationships of editorialists with brand-name pharmaceutical companies, which are not always
disclosed.”

Nearly half the trials (23 out of 47) and nearly all the editorials and commentaries they reviewed did not reveal where the funding came from, noted
Kesselheim and colleagues, who also wrote that:

“We identified numerous studies that evaluated differences in clinical outcomes with generic and brand-name medications. Our results suggest that it
is reasonable for physicians and patients to rely on FDA bioequivalence rating as a proxy for clinical equivalence among a number of important
cardiovascular drugs, even in higher-risk contexts such as the NTI drug warfarin.”

“These findings also support the use of formulary designs aimed at stimulating appropriate generic drug use. To limit unfounded distrust of generic
medications, popular media and scientific journals could choose to be more selective about publishing perspective pieces based on anecdotal evidence
of diminished clinical efficacy or greater risk of adverse effects with generic medications. Such publications may enhance barriers to appropriate
generic drug use that increase unnecessary spending without improving clinical outcomes,” they added.

“Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease: A Systematic Review and Meta-
analysis.”
Aaron S. Kesselheim; Alexander S. Misono; Joy L. Lee; Margaret R. Stedman; M. Alan Brookhart; Niteesh K. Choudhry; William H. Shrank.
JAMA. Vol 300, No 21, pp 2514-2526, December 3, 2008.

Click here for Abstract.

Sources: JAMA.

Written by: Catharine Paddock, PhD

View drug information on Warfarin Sodium tablets.

Continue reading →

Brain cells can adopt a new chemical code in response to cues from the outside world, scientists working with tadpoles at the University of California, San Diego report in the journal Nature this week.

The discovery opens the possibility that brain chemistry could be selectively altered by stimulating specific circuits to remedy low levels of neural chemicals that underlie some human ailments.

Dark tadpoles don pale camouflage when exposed to bright light. The researchers have now identified cells in the tadpole brain that respond to illumination by making dopamine, a chemical message, or neurotransmitter, recognized by the system that controls pigmentation.

“We used to think activity turned a switch to specify which transmitters a neuron would use only in early development,” said co-author Davide Dulcis, a postdoctoral fellow in neurobiology who designed and conducted the experiments. “But this is happening after hatching.”

The cells, found in a cluster called the suprachiasmatic nucleus, connect to a gland that releases a hormone that disperses pigments to darken skin. Dopamine squelches hormone release leaving pigments tightly packed in skin cells and the tadpoles nearly transparent.

“The behavior meets an ecological need.” Dulcis said. “Pale tadpoles are difficult for predators to see in a bright environment, so the faster the tadpoles change their pigmentation, the better they are able to survive.”

Cells in the core of the cluster always make dopamine, but a ring of surrounding cells normally don’t, even though they are connected to the gland.

Bright light alters this pattern, however. After just two hours, cells in the surrounding ring show signs of making the new neurotransmitter. Because they are already hooked up to the hormone-producing target, illumination can result in noticeably paler tadpoles in as little as ten minutes.

“The new dopamine neurons are not simply activated at random,” said co-author Nicholas Spitzer, a professor of neurobiology who leads the research group. “It’s as if they are a kind of national guard, waiting in reserve to be called out. There’s a pool of neurons waiting for the right sensory stimulus to be called into action and to adopt a new transmitter.”

The signal-switching cells receive a link directly from the eye and are part of a brain circuit shared by a variety of animals from bony fish to humans. Although these cells don’t contribute to vision, they do monitor light levels for other purposes, particularly for coordinating daily rhythms of physiology and behavior.

Activity might alter brain chemistry in other circuits as well, the researchers say. Light helps people who experience seasonal affective disorder, for example. Their symptoms of depression, which descend during long winter nights, lift in summer and also abate when they are regularly exposed to bright light, a therapy that can be as effective as anti-depressant drugs.

“Maybe it’s the case that for many neurons there is additional circuitry that can be activated under certain circumstances,” Spitzer said.

Depleted brain chemistry underlies several diseases, including Parkinson’s. If a reserve pool of neurons could be identified and recruited by stimulating particular neural circuitry some of the side effects that stem from flooding the entire brain and body with drugs designed to boost levels of specific neurotransmitters might be avoided, he said.

The National Institutes of Health funded the study.

Continue reading →