Hydro-Fracking: Fact Vs. Fiction

In communities across the U.S., people are hearing more and more about a controversial oil and gas extraction technique called hydraulic fracturing -- aka, hydro-fracking. Controversies pivot on some basic questions: Can hydro-fracking contaminate domestic wells? Does it cause earthquakes? How can we know? What can be done about these things if they are true?

  

"When people talk about contamination from hydraulic fracturing, for instance, they can mean a lot of different things," says hydrogeologist Harvey Cohen of S.S. Papadopulos & Associates in Bethesda, Maryland. "When it's what's happening near their homes, they can mean trucks, drilling machinery, noise." These activities can potentially lead to surface water or groundwater contamination if there are, for example, accidental fuel spills. People also worry about fracking fluids leaking into the aquifers they tap for domestic or municipal water.

On the other hand, when petroleum companies talk about risks to groundwater from hydro-fracking, they are often specifically referring to the process of injecting fluids into geologic units deep underground and fracturing the rock to free the oil and gas it contains, says Cohen. This is a much smaller, much more isolated part of the whole hydraulic fracturing operation. It does not include the surface operations -- or the re-injection of the fracking waste fluids at depth in other wells, which is itself another source of concern for many.

But all of these concerns can be addressed, says Cohen, who will be presenting his talk on groundwater contamination and fracking on the morning of Nov. 7. For instance, it has been proposed that drillers put non-toxic chemical tracers into their fracking fluids so that if a nearby domestic well is contaminated, that tracer will show up in the well water. That would sort out whether the well is contaminated from the hydro-fracking operations or perhaps from some other source, like a leaking underground storage tank or surface contaminants getting into the groundwater.

"That would be the 100 percent confident solution," says Cohen of the tracers.

Another important strategy is for concerned citizens, cities, and even oil companies to gather baseline data on water quality from wells before hydro-fracking begins. Baseline data would have been very helpful, for example, in the case of the Pavillion gas field the Wind River Formation of Wyoming, according to Cohen, because there are multiple potential sources of contaminants that have been found in domestic wells there. The Pavillion field is just one of multiple sites now being studied by the U.S. Environmental Protection Agency (EPA) to learn about past and future effects of hydro-fracking on groundwater.

The same pre-fracking science approach is being taken in some areas to evaluate the seismic effects of disposing of fracking fluids by injecting them deep underground. In Ohio and Texas, this disposal method has been the prime suspect in the recent activation of old, dormant faults that have generated clusters of low intensity earthquakes. So in North Carolina, as well as other places where fracking has been proposed, some scientists are scrambling to gather as much pre-fracking seismic data as possible.

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Plant-Based Foods May Offer Reduced Risk for Aggressive Prostate Cancer

President George W. Bush made no secret that he detested broccoli. With all due respect to our former leader, researchers have found one more great reason to add fruits, vegetables, herbs and tea to your diet.

A study by Susan Steck of the Arnold School of Public Health finds that a high intake of flavonoids, a group of compounds found in plants, may lower the risk for highly aggressive prostate cancer.

"Incorporating more plant-based foods and beverages, such as fruits, vegetables, herbs and tea, into the diet may offer some protection against aggressive prostate cancer," said Steck, an associate professor at the Arnold School and an affiliated scholar with the Center for Research in Health Disparities.

"Filling your plate with flavonoid-rich foods is one behavior that can be changed to have a beneficial impact on health," she said.

Steck presented her findings at the International Conference on Frontiers in Cancer Prevention Research. The annual event is sponsored by the American Association for Cancer Research, whose mission is to prevent and cure cancer through research, education, communication and collaboration.

Prior preclinical studies have shown that flavonoids have beneficial effects against prostate cancer, but few studies have examined the effect of flavonoids on prostate cancer in humans.

Steck and her colleagues used data from 920 African-American men and 977 white men in the North Carolina-Louisiana Prostate Cancer Project who were newly diagnosed with prostate cancer. Participants completed a self-reported dietary history questionnaire to assess flavonoid intake, which was measured using the U.S. Department of Agriculture's 2011 Database for the Flavonoid Content of Selected Foods.

Men with the highest total intake of flavonoids had a 25 percent lower risk for aggressive prostate cancer compared with those men with the lowest flavonoid intake.

"We found that higher total flavonoid intake was associated with reduced odds for aggressive prostate cancer in both African-American and European-American men, but no individual subclass of flavonoids appeared to be protective independently, suggesting that it is important to consume a variety of plant-based foods in the diet, rather than to focus on one specific type of flavonoid or flavonoid-rich food," Steck said.

In addition, the risk for aggressive prostate cancer was even lower in those men younger than 65 and in current smokers with the highest levels of flavonoid intake. Dietary questionnaire results revealed that citrus fruits and juices, such as oranges and grapefruits, tea, grapes, strawberries, onions and cooked greens were the top contributors to total flavonoid intake among the participants. "The results support public health recommendations and guidelines from organizations such as the American Institute for Cancer Research to consume a more plant-based diet," Steck said. "In particular, consuming more flavonoid-rich foods may be beneficial for those people who are at increased risk for cancer, such as smokers."

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Bacteria Talk to Each Other and Our Cells in the Same Way, Via Molecules

Bacteria can talk to each other via molecules they themselves produce. The phenomenon is called quorum sensing, and is important when an infection propagates. Now, researchers at Linköping University in Sweden are showing how bacteria control processes in human cells the same way.

The results are being published inPLoS Pathogens with Elena Vikström, researcher in medical microbiology, as the main author.

Bacteria 'talk'

When the announcement goes out, more and more bacteria gather at the site of the attack -- a wound, for example. When there are enough of them, they start acting like multicellular organisms. They can form biofilms, dense structures with powers of resistance against both antibiotics and the body's immune defense system. At the same time, they become more aggressive and increase their mobility. All these changes are triggered when the communication molecules -- short fatty acids with the designation AHL -- fasten to receptors inside the bacterial cells; as a consequence various genes are turned on and off.

AHL can wander freely through the cell membrane, not just in bacterial cells but also our own cells, which can be influenced to change their functions. In low concentrations white blood cells, for example, can be more flexible and effective, but in high concentrations the opposite occurs, which weakens our immune defenses and opens the door for progressive infections and inflammations.

A team at Linköping University is the first research group to show how AHL can influence their host cells. Using biochemical methods, the researchers have identified a protein designated IQGAP, which they single out as the recipient of the bacteria's message, and something of a double agent.

"The protein can both listen in on the bacteria's communication and change the functions in its host cells," Vikström says.

Their laboratory studies were carried out on human epithelial cells from the intestines, which were mixed with AHL of the same type produced by Pseudomonas aeruginosa, a tough bacterium that causes illnesses in places like the lungs, intestines, and eyes. With the help of mass spectrometry, they have been able to see which proteins bind AHL.

"We have proof that physical contact between bacteria and epithelial cells is not always required; the influence can happen at a distance," Vikström says.

The team's discovery can open the door to new strategies for treatment where antibiotics cannot help. One possibility is designing molecules that bind to the receptor and block the signal path for the bacteria -- something like putting a stick in a lock so the key won't go in. It's a strategy that could work with cystic fibrosis, for example, an illness where sticky mucus made of bacterial biofilm and large amounts of white blood cells is formed in the airways.

  

Journal Reference:

1.      Thommie Karlsson, Maria V. Turkina, Olena Yakymenko, Karl-Eric Magnusson, Elena Vikström. The Pseudomonas aeruginosa N-Acylhomoserine Lactone Quorum Sensing Molecules Target IQGAP1 and Modulate Epithelial Cell Migration. PLoS Pathogens, 2012; 8 (10): e1002953 DOI: 10.1371/journal.ppat.1002953

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Cigarette Smoke Boosts Virulence in Staphylococcus Aureus

Exposure to cigarette smoke has long been associated with increased frequency of respiratory infections -- which are harder to treat in smoke-exposed people than in those who lack such exposures. Now Ritwij Kulkarni of Columbia University, New York, NY, and colleagues show that cigarette smoke actually boosts virulence of Staphylococcus aureus bacteria.

Their study appears in the November 2012 issue of the journal Infection and Immunity.

S. aureus is a normally harmless inhabitant of the upper respiratory tract, but one which can morph into a dangerous pathogen capable of causing severe, and even fatal infections, says Kulkarni. The new research shows that cigarette smoke can aid and abet that transformation.

Cigarette smoke does so by enhancing S. aureus' ability to form biofilms, which are an important virulence factor, according to the study. The research showed further that reactive oxygen species, such as H2O2, which are concentrated in cigarette smoke, drive biofilm formation, says Kulkarni.

Kulkarni notes that a recent paper, from another group, showed that reactive oxygen species suppress the gene regulator, "Accessory Gene Regulator," or agr for short. "That fits nicely with our story," he says. "We think control of biofilm formation [and of numerous other virulence factors inS. aureus] proceeds via agr."

Journal Reference:

1.      R. Kulkarni, S. Antala, A. Wang, F. E. Amaral, R. Rampersaud, S. J. LaRussa, P. J. Planet, A. J. Ratner.Cigarette Smoke Increases Staphylococcus aureus Biofilm Formation via Oxidative Stress. Infection and Immunity, 2012; 80 (11): 3804 DOI: 10.1128/IAI.00689-12

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Insect-Repelling Compounds Discovered in Folk Remedy Plant, Jatropha

A tip about a folk remedy plant used in India and Africa to ward off bugs has led to the discovery of insect-repelling compounds.

U.S. Department of Agriculture (USDA) scientists have identified components of Jatropha curcas seed oil that are responsible for mosquito repellency. Researchers at the Agricultural Research Service (ARS) Natural Products Utilization Research Unit (NPURU) in Oxford, Miss., often find effective plant-derived compounds to deter insects by gathering plants in the wild and investigating those used in traditional folk remedies. ARS is USDA's principal intramural scientific research agency.

After learning that people in India burn J. curcas seed oil in lamps to keep insects out of their homes and other areas, NPURU chemist Charles Cantrell extracted smoke from the plant in a laboratory and analyzed its properties. Free fatty acids and triglycerides were among a number of active compounds found to be effective at preventing mosquitoes from biting.

Researchers have known for some time that fatty acids repel insects, but this was the first known report that identified triglycerides as having mosquito repellent activity, according to Cantrell.

Working closely with colleagues at ARS and the National Center for Natural Products Research at the University of Mississippi, Cantrell is exploring additional promising compounds from other plants. By combining these or similar compounds from other plants with those in Jatropha species, scientists might be able to develop a more effective product.

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Novel Reference Material to Standardize Gene Therapy Applications

The introduction of a new, fully characterized viral vector for use as reference material to help standardize gene therapy protocols in research applications and human clinical trials is described in an article in Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc.

The growing popularity in the gene therapy community of using recombinant adeno-associated virus (rAAV) vectors as vehicles to transfer a gene of interest into a host cell has led to increasing numbers of human clinical trials and animal studies with rAAV. In the past, the absence of standardization -- such as for rAAV potency and dosing -- have made it difficult for researchers and clinicians to compare their protocols and the results of gene therapy experiments. The availability of this rAAV reference standard will allow vector parameters to be expressed in common units, vector doses administered by different investigators to be normalized to an agreed-upon standard, and laboratories to calibrate their internal standards to a common reference material.

Martin Lock, from the Gene Therapy Program at the University of Pennsylvania (Philadelphia) and colleagues from several major medical and research institutions around the world, describe the development of reference standard in the article "Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material."

The American Type Culture Collection will make the rAAV2 reference standard material available to the scientific community. AAV serotype 2 was selected as the basis for the reference material because it is the best characterized AAV subtype. The material has been thoroughly analyzed and found to be free of microbial contamination. During development of the rAAV2 reference standard samples were distributed to 16 laboratories worldwide for extensive analysis and characterization.

"The development of a reference standard for an AAV vector is an important step towards the eventual commercial development of this important vector platform," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, in Philadelphia.

Journal Reference:

1.      Martin Lock, Susan McGorray, Alberto Auricchio, Eduard Ayuso, E. Jeffrey Beecham, Véronique Blouin-Tavel, Fatima Bosch, Mahuya Bose, Barry J. Byrne, Tina Caton, John A. Chiorini, Abdelwahed Chtarto, K. Reed Clark, Thomas Conlon, Christophe Darmon, Monica Doria, Anne Douar, Terence R. Flotte, Joyce D. Francis, Achille Francois, Mauro Giacca, Michael T. Korn, Irina Korytov, Xavier Leon, Barbara Leuchs, Gabriele Lux, Catherine Melas, Hiroaki Mizukami, Philippe Moullier, Marcus Müller, Keiya Ozawa, Tina Philipsberg, Karine Poulard, Christina Raupp, Christel Rivière, Sigrid D. Roosendaal, R. Jude Samulski, Steven M. Soltys, Richard Surosky, Liliane Tenenbaum, Darby L. Thomas, Bart van Montfort, Gabor Veres, J. Fraser Wright, Yili Xu, Olga Zelenaia, Lorena Zentilin, Richard O. Snyder.Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material. Human Gene Therapy, 2010; 100916064126038 DOI:10.1089/hum.2009.223

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Dexpramipexole promising in phase II trial for Lou Gehrig's disease

Results of a phase II clinical trial shows the drug dexpramipexole slows the progression of amyotrophic lateral sclerosis (ALS), otherwise known as Lou Gehrig’s disease.

Currently, there are only two drugs that treat ALS. The disease progressively causes death of nerve cells in the brain and spinal cord that ultimately leads to paralysis and death from respiratory failure.

Merit Cudkowicz, MD, director of the Massachusetts General Hospital (MGH) Neurology Clinical Trials Unit and ALS Center, lead author of the study said, "We need more therapies to slow, halt and ultimately reverse the course of disease and also therapies to treat the symptoms."

The two drugs available for ALS treatment are riluzole, which extends life about 10 percent, and Nuedexta, which treats the emotional instability associated with Lou Gehrig’s disease.

Earlier this year, researchers from Northwestern University announced a breakthrough in understanding the cause of ALS, or Lou Gehrig’s disease. In all cases, the disease occurs as the result of a breakdown of protein recycling in the brain and spinal cord. The Northwestern finding should also lead to new treatments within the next 5 to 10 years.

For the trial, patients were tested in two phases. The first group of 102 patients was split into 4 groups; all had been recently diagnosed with ALS.

Patients in the study were given either and oral placebo or dexpramipexole at total daily dosages of 50, 150 or 300 mg for 12 weeks.

After 12 weeks the participants were given just placebo for four weeks; then split again into two groups and given either 50 or 300 mg of dexpramipexole for 24 weeks.

The results showed 300mg of the experimental drug slowed progression of Lou Gehrig’s 30 percent, compared to placebo. The finding was the same in the second stage of the study.

"Since individual participants could have been in different treatment groups in the first and second stages of the study, seeing the same dose-dependent differences at both stages gives us confidence in the data. In a way, this was two supportive studies in one trial design," says Cudkowicz.

The drug is now in phase III clinical trials. Dexpramipexole is licensed for development by Biogen Idec and was initially developed by Knopp Biosciences of Pittsburgh.

Dexpramipexole seems to work for treatment of Lou Gehrig’s disease by protecting mitochondria in nerve cells from becoming dysfunctional. In the phase II trial, the drug was shown to extend lifespan for patients with ALS by 30 percent

-November 22, 2011.

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