Science Weekly: The arsenic bacterium that could help find life in outer space

Filed Under Uncategorized | Comments Off on Science Weekly: The arsenic bacterium that could help find life in outer space

An arsenic-loving bacterium; an augmented reality dinosaur; what your finger-length means; and should science journals be free?

Target e*CRF® Version 2

Target Health is pleased to announce the development of Target e*CRF Version 2 is on schedule for release by 31 January 2011. To bring Target e*CRF Version 2 in-house, it is estimated that there will be a need to have a minimum of 2 experienced .net programmers with MSSQL experience, who also have a knowledge of clinical research and data management. Companies will also need a minimum of 1 tester. Even if Target Health hosts the software and applications, companies will need IT people to maintain the local development and testing environments.

It is estimated that it will take no more than a month from start to end to get programmers trained and operational. Target Health will of course provide the necessary support, if additional training is necessary to address unique programming challenges.

Target Health will provide the following as part of training over no more than a 3-week period:

  1. Software installation
  2. Setting up a study
  3. Creating forms
  4. Creating edit checks
  5. Creating reports
  6. Creating the study navigation
  7. Launching a study


Target Health will use the system first internally, as we do with all of our software. Target e*CRF Version 2 will be available to our customers by March 15 2011.

Other software products include:

  1. Target Document®
  2. Target Encoder®
  3. Target CTMS®
  4. Target Pharmacovigilance®
  5. Target e*CTR® (eClinical Trial Record)
  6. Target Monitoring Reports™
  7. Target Randomization™
  8. Target Batch Edit Checks™
  9. Target Newsletter®


For more information about Target Health contact Warren Pearlson (212-681-2100 ext 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

Tooth Decay a Thing of the Past?

The enzyme responsible for dental 1) ___ sticking to teeth, has been deciphered.

Two Netherlands professors Bauke Dijkstra and Lubbert Dijkhuizen have deciphered the structure and functional mechanism of the glucansucrase enzyme that is responsible for dental plaque sticking to teeth. This knowledge will stimulate the identification of substances that inhibit the enzyme. Just add that substance to 2) ___, or even sweets, and caries will be a thing of the past. The results of the research have been published this week in the journal Proceedings of the National Academy of Sciences (PNAS).

The University of Groningen researchers analyzed glucansucrase from the lactic acid bacterium Lactobacillus reuteri, which is present in the human mouth and 3) ___ tract. The bacteria use the glucansucrase enzyme to convert sugar from food into long, sticky sugar chains. They use this glue to attach themselves to tooth enamel. The main cause of tooth decay, the bacterium Streptococcus mutans, also uses this enzyme. Once attached to tooth enamel, these bacteria ferment sugars releasing 4) ___ that dissolve the calcium in teeth. This is how caries develops.


Three dimensional structure

Using protein crystallography, the researchers were able to elucidate the 3D structure of the enzyme. The Groningen researchers are the first to succeed in crystallizing glucansucrase. The crystal structure has revealed that the folding mechanism of the 5) ___ is unique. The various domains of the enzyme are not formed from a single, linear amino acid chain but from two parts that assemble via a U-shaped structure of the chain; this is the first report on such a folding mechanism in the literature.


Functional mechanism

The unravelling of the 3D structure provided the researchers with detailed insight into the functional mechanism of the enzyme. The 6) ___ splits sucrose into fructose and glucose and then adds the glucose molecule to a growing sugar chain. Thus far the scientific community assumed that both processes were performed by different parts of the enzyme. However, the model created by the Groningen researchers has revealed that both activities occur in the same active site of the enzyme.



Dijkhuizen expects that specific inhibitors for the glucansucrase enzyme may help to prevent attachment of the bacteria to the tooth 7) ___. Information about the structure and functional mechanism of the enzyme is crucial for developing such inhibitors. Thus far, such research has not been successful, states Dijkhuizen: “The various inhibitors studied not only blocked the glucansucrase, but also the digestive enzyme amylase in our saliva, which is needed to degrade starch.”


The crystal structure also provides an explanation for this double inhibition. The data published by the Groningen scientists shows that glucansucrase proteins most likely evolved from amylase enzymes that degrade 8) ___.


Toothpaste and sweets

Dijkhuizen points out that in future glucansucrase inhibitors may be added to toothpaste and mouthwash. And that it may even be possible to add them to 9) ___. An inhibitor might prevent those sugars released in the mouth, that cause damage. However, Dijkhuizen doesn’t expect that toothbrushes have had their day. It will always be necessary to clean your teeth.


ANSWERS: 1) plaque; 2) toothpaste; 3) digestive; 4) acids; 5) protein; 6) enzyme; 7) enamel; 8) starch; 9) sweets

Heart Transplants (1967 to present)

Figure A shows where the diseased heart is cut for removal. Figure B shows where the transplanted healthy heart is sutured (stitched) to the recipient’s arteries and veins

Research has shown that the longer it takes to remove a heart and transplant it, the greater the patient’s chance of death or heart disease. Despite advances in heart transplantation, the way hearts are moved around the U.S. and most places remains low-tech. It’s been done this way for more than four decades, ever since the first U.S. heart transplant was performed on Dec. 6, 1967

Once a heart is harvested, for a transplant, it’s a race against time. A heart can stay fresh in the cooler for 4 to 6 hours before it starts to deteriorate. Currently, a team of doctors and organ recovery specialists stuffs an off-the-shelf picnic cooler with ice and jets off at odd hours to a donor hospital. They inject a chemical to stop the organ and preserve it in the ice chest for the trip home.


The new high-tech heart box circulates blood from the donor to the heart so that it continues throbbing while in transit from hospital to hospital. It may also potentially help ease the organ shortage crisis. Some 3,000 Americans are currently on the heart transplant waiting list. Last year, 359 died waiting for a heart. The thinking is that hearts may be in better condition if they’re kept beating instead of being cooled in ice. And if hearts can be monitored outside the body, proponents say this may help increase the organ pool by allowing less-than-perfect hearts to be transplanted.

Recent heart transplant surgery began like any other. The call came in to Ronald Reagan UCLA Medical Center shortly before 4 p.m. on Aug. 24. After examining the heart, they stopped it to remove it. Instead of packing the heart on ice, doctors transferred it to a box filled with blood and nutrients to revive it. The box was then tucked inside a portable machine for transport. On the way back to UCLA, the heart was closely checked to make sure it was stable. In the meantime, the recipient was placed on a heart-lung machine as doctors took out her failing heart. Surgeons re-stopped the donor heart and sewed it into the recipient.

The world’s first beating heart transplant was performed in Germany in 2006, using an organ box invented by TransMedics Inc., a private medical device company in Andover, Mass., as part of a multi-center study in Europe. The company followed up with a pilot study in the U.S. It is currently funding the UCLA-led experiment, which will enroll 128 patients nationwide, randomly chosen to get a beating heart transplant or the traditional kind. About 100 patients, mostly in Europe, have had a beating heart transplant.

Early signs from two European experiments involving 54 patients are encouraging. There has been 97% survival a month after the operation and few episodes of rejection and heart-related complications. Transplant doctors with no connection to the research note that the current system works despite the antiquated way hearts are carted around. Before beating heart transplants can be routine, researchers must not only prove that the technology can preserve hearts better and longer, but that recipients also have improved survival and health than if they had a regular heart transplant.

There’s also the issue of cost. A typical heart transplant in the U.S. costs about $787,000 including hospital stay and anti-rejection drugs. An Igloo cooler costs $35 compared with the heart box, which is sold in Europe for about $200,000. The interior is not reusable so there’s an added expense each time a hospital does such an operation. Source:

Young Women with Menopause-Like Condition at Risk for Depression

Depression is a serious medical illness affecting the brain which involves more than feeling blue or sad for a few days. Symptoms include persistent feelings of sadness, difficulty sleeping or over sleeping, energy loss, and feelings of worthlessness. Primary ovarian insufficiency, or POI, results in a menopause-like condition years before normal menopause begins-sometimes as early as the teens or twenties. Women with POI stop producing normal amounts of reproductive hormones, develop hot flashes, and typically become infertile.

According to a study from the National Institutes of Health and published on line in the Journal of Clinical Endocrinology and Metabolism (3 November 2010), young women with the menopause-like condition, primary ovarian insufficiency, are much more likely than other women to experience depression at some point during their lives. The study authors evaluated 174 women with POI and found that 67% either were currently clinically depressed or had been depressed at least one time in their lives. The authors noted that this proportion was more than twice the rate of depression found by a national survey of women in the general population. The finding suggests that all women diagnosed with the condition should be evaluated for depression.

For the study, over a period of nearly five years, the investigators asked 174 women with POI to respond to a standard set of interview questions on past or current incidents of major, minor, or long-term depression. The women also were asked when they were diagnosed with POI and when they first noticed the pattern of irregular menstrual cycles believed to signal the onset of POI.

The study was unable to determine why women with POI are more likely than other women to experience depression. The investigators cited results of a previous study, which had suggested that depression might trigger physical changes that ultimately lead women to develop POI. However, in the current study, more than 73% of women with POI first experienced depressive symptoms after developing the irregular menstrual cycles believed to be an indicator of impending POI.

The findings did not support the hypothesis that most women with POI become depressed after they are told of their diagnosis, when they learn that they will likely be infertile. In the current study, more than 68% of patients with POI who had depression had become depressed after the onset of irregular menstrual cycles, but before receiving the diagnosis of POI.

In a previous study, the authors found that women entering natural menopause at an appropriate age are at greater risk of depression late in the menopause transition, when estrogen levels are particularly low. The authors noted that studies of women undergoing natural menopause have found that estrogen supplements relieve symptoms of depression in some women. The authors added that it is possible that estrogen supplements might relieve symptoms of depression in women with POI and that future studies are needed to help determine whether hormonal changes, perhaps combined with a particular genetic makeup, might predispose some women to depression.

Body-Mass Index and Mortality Among 1.46 Million White Adults

Obesity has emerged as a leading public health concern in the United States. It has been well-established that people who are obese face increased risks of death from heart disease, stroke, and certain cancers. Currently, two-thirds of U.S. adults are overweight or obese. Even more worrisome, 17% of women and 11% of men are severely obese.

BMI, the most commonly used measure for body fat, is calculated by dividing a person’s weight in kilograms by the square of his/her height in meters (kg/m2). Current guidelines from the U.S. Centers for Disease Control and Prevention, and the World Health Organization define a normal BMI range as 18.5 to 24.9. Overweight is defined as a BMI of 25.0 to 29.9; obesity is defined as a BMI over 30.0; and severe obesity is defined as BMI 35 or higher.

According to an article published in the New England Journal of Medicine (2010;363:2211-2219), looking at deaths from any cause found that a body mass index (BMI) between 20.0 and 24.9 is associated with the lowest risk of death in healthy non-smoking adults. Investigators also provided precise estimates of the increased risk of death among people who are overweight and obese. Previous studies that examined the risks from being overweight were inconclusive, with some reporting only modestly increased risks of death and others showing a reduced risk. Also, the precise risks for different levels of obesity were uncertain.

In this large analysis, investigators pooled data from 19 long-term studies designed to follow participants over time, from 5 to 28 years, depending on the study. Results showed that healthy women who had never smoked and who were overweight were 13% more likely to die during the study follow-up period than those with a BMI between 22.5 and 24.9. Women categorized as obese or severely obese had a dramatically higher risk of death. As compared with a BMI of 22.5 to 24.9, the researchers report a 44% increase in risk of death for participants with a BMI of 30.0 to 34.9; an 88% increase in risk for those with a BMI of 35.0 to 39.9; and a 2.5 times (250%) higher risk of death for participants whose BMI was 40.0 to 49.9. Results were broadly similar for men. Overall for men and women combined, for every five unit increase in BMI, the researchers observed a 31% increase in risk of death.

The Study observed similar patterns of risk even after accounting for differences in alcohol consumption, physical activity, and education level. The increased risk of death for a BMI of 25 or greater was also seen in all age groups, although it was more prominent for those who were overweight or obese before age 50.

The investigators gathered information about BMI and other characteristics from questionnaires participants completed at the beginning of each study. Causes of death were obtained from death certificates or medical records. This analysis was restricted to non-Hispanic whites aged 19 to 84. The investigators noted the relationship between BMI and mortality may differ across racial and ethnic groups. Other efforts are underway to study the effect of BMI on mortality in other racial and ethnic groups.

Drug-Like Compound Stops Thyroid Overstimulation

In Graves’ disease, the thyroid gland never stops. Thyroid-stimulating antibodies bind to receptors, activating them to keep the thyroid hormone coming and coming – like a broken traffic light stuck on green – and causing the body problems in regulating energy, controlling other hormones and maintaining cells throughout the body. Graves’ disease is an autoimmune disorder, causing the body’s immune system to act against the body’s own cells and organs. Graves’ disease typically first occurs in people under 40 and affects approximately 1% of the U.S. population, with women five to 10 times more likely than men to have Graves’ disease.

Though treatments are available for hyperthyroidism caused by Graves’ disease, including surgery, radioactive iodine, and antithyroid drugs, the relapse rates for these treatments are 5%, 21% and 40%, respectively, and each comes with unfavorable side effects.

According to an article published online in Journal of Clinical Endocrinology and Metabolism (2 December 2010), a compound has been identified that can prevent overproduction of thyroid hormone, a finding that brings researchers one step closer to improving treatment for Graves’ disease. The chemical compound binds to the receptors and acts as an antagonist, keeping the stimulating antibodies from their work and potentially allowing the thyroid cells to revert to normal function. The antagonist has not yet been tested in animals or people and still has multiple steps of toxicology and safety testing before it may be ready for human trials.

The newly discovered compound, which is a receptor antagonist, may have the added benefit of helping those with eye problems caused by Graves’ disease – called Graves’ ophthalmopathy – experienced by more than 25% of people with the disease. Eye problems may include painful swelling in the eye sockets, double vision, tears or itchy eyes, and protruding eyes with swollen eyelids that can’t be easily shut, increasing the risk for eye diseases. Because the swelling in the eyes is thought to be associated with the same overstimulation of receptors caused by the same thyroid-stimulating antibodies as in the thyroid, the potential thyroid treatment may have the added benefit of treating the eye problems as well.

The research team is also at work on the flip side of thyroid regulation. By researching the thyroid-stimulating hormone receptor, they are hoping to use drug-like compounds to stimulate this receptor to treat people with thyroid cancer, who need more stimulation of thyroid cancer cells to increase the efficacy of iodine radiation. They’ve tested their discovery in mice and hope to perform pre-clinical studies and to develop human trials in the foreseeable future.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

A New Environment, a Changed Act? The Affordable Care Act and the New Congress

While the pharmaceutical industry is data driven, there are times when the data required for a decision simply don’t exist. Often the best thing to do in those situations is to await better data, but sometimes that is not an option. Other times, it is simply fun to speculate.

While all of us are impacted by the healthcare environment, it is both interesting and potentially helpful to consider how some of the recent changes may impact the recently enacted Affordable Care Act.

While the new environment created by the November elections has already had an impact on health care “rhetoric”, the more compelling question is whether there will be meaningful changes in the Affordable Care Act itself. Given the President Obama’s commitment, it seems highly likely that the Affordable Care Act will remain the law of the land. However, the requirement for Congressional appropriations to implement key elements in the law allows opportunities to interfere with various components of the Act.

Reviewing key debates leading up to passage of the Act identifies potential elements for modification by the new Congress. Concerns voiced about Government involvement in medical decisions, along with budgetary pressures to identify program cuts (however small the dollar amounts), unfortunately place the innovative delivery system pilot programs and the data collecting initiatives in the Act at risk. These include the Patient Centered Outcomes Research Institute and the Center for Medicare/Medicaid Innovation.

Will these initiatives, long promoted by academics and health services researchers, be perceived as low hanging “cost-containment” fruit to be plucked, or instead recognized as opportunities for meaningful improvements in the system? Only time will tell, but since both have the potential to significantly impact the development and marketing of pharmaceuticals and devices, it is a debate worth watching. Mark L. Horn, MD, CMO, Target Health Inc.

For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.