St. Jude Children’s Research Hospital scientists lead effort that identifies a novel way statins protect cells from a host of bacterial toxins

New research suggests a family of widely used cholesterol-lowering drugs might help protect individuals from serious illness following bacterial infection, including the pneumococcal infections that pose a deadly threat to those with sickle cell disease.

Research led by St. Jude Children’s Research Hospital investigators reported that drugs called statins employ several methods to dampen inflammation and block pneumococcus and certain other bacteria from infecting cells and spreading throughout the body. Elaine Tuomanen, M.D., St. Jude Infectious Diseases chair, said those methods include a newly identified mechanism that statins use to protect healthy cells by blocking the toxicity of an entire class of bacteria. Along with pneumococcus, that class includes diphtheria, tetanus, listeria and group A streptococcus, which is also known as the flesh-eating bacterium.

Tuomanen is co-senior author of the study with Carlos Orihuela, Ph.D., University of Texas Health Science Center at San Antonio (UTHSCSA). The work is published in the January 19 advanced, online edition of The Journal of Clinical Investigation.

The results provide the foundation for a possible future study to determine if statins, already widely used to lower cholesterol in adults, might protect children with sickle cell disease (SCD) from serious pneumococcal infection. SCD is an inherited blood disorder. The findings also suggest statins might protect others at high risk for pneumonia due to chronic inflammation of the lungs or blood vessels.

In this study, scientists reported that statins prolonged the lives of mice with sickle cell disease following infection with the pneumococcal bacteria. Researchers also reported that a day after being infected, the treated mice had fewer bacteria in their lungs and blood, suggesting statins slowed the spread of the infection.

Tuomanen said statins did not cure the mice, but prolonged their survival. She said the extra time might make a life-or-death difference in humans by keeping patients alive long enough for other medications to kill the bacteria.

The research reflects the long-standing interest of St. Jude investigators in both sickle cell and pneumococcal and other infectious diseases. Tuomanen said it is also an example of the insights gained when basic and clinical investigators collaborate.

Pneumococcal infection is the leading cause of lethal pneumonia in children worldwide. The bacterium poses an even greater threat to children with SCD. They are 400 times more likely than their healthy counterparts to develop widespread, potentially fatal pneumococcal infections.

Sickle cell is the most common genetic disorder worldwide. In the U.S., the disease most often strikes those of African ancestry. About one in every 375 African American newborns inherits the mistake in instructions for assembling the hemoglobin protein, which is responsible for ferrying oxygen throughout the body. As a result, their red blood cells sometimes change from a pliable, disc shape to a brittle, sickled shape. The sickled cells are unable to move easily through tiny blood vessels, disrupting circulation and leaving affected individuals at risk for a variety of debilitating and deadly problems, including infections.

The risk posed by the pneumococcus is so great that young sickle cell patients are prescribed a daily dose of penicillin in hopes of preventing the infection. Investigators noted that emergence of pneumococcal bacteria resistant to penicillin underscores the need for new prevention tools.

Statins interfere with the liver’s ability to make cholesterol. Several years ago researchers noted possible links between statins and a reduced risk of respiratory infections and sepsis.

In this study, researchers showed statins work in part by dampening expression of the protein found on the surface of cells that pneumococcus uses to gain entry into the cells. That protein is called the platelet-activating factor receptor or PAFr. A variety of factors influence how much PAFr is found on the surface of cells. The chronic inflammation associated with sickle cell and certain other diseases leads to increased PAFr production by cells lining the blood vessels and in the lungs.

Investigators used several methods to show statins reduced the number of PAF receptors on the surface of cells both in the laboratory and in the lungs of mice with SCD. In the laboratory, the suppression of the receptor was reversible with the addition of a compound that blocked statin activity.

But Jason Rosch, Ph.D., said PAFr turned out to be just part of the story. Rosch is a St. Jude postdoctoral fellow and the paper’s lead author.

Investigators reported statins even helped sickle cell mice that lacked the genetic instructions for making the mouse version of PAFr battle pneumococcal infection more effectively. The statin-treated mice lived longer and had fewer bacteria in their blood. The drug had no impact on mice that lacked PAFr, but did not have sickle cell disease. Rosch said that suggested statins work in part by reducing inflammation associated with sickle cell disease.

Researchers also found statins interfere with the mechanism by which poisons, or toxins, pneumococcus and other bacteria produce are taken up into cells. Those toxins rely on cholesterol in the cell membrane to attach to the cell and form an opening called a pore to gain entry into the cell and ultimately destroy it. Working in both statin-treated cells in the laboratory and in mice, researchers reported that after statin treatment bacterial toxins could bind to cells, but no pore formed and cell death was disrupted.

Mice treated with statins suffered less damage when the bacterial toxin was injected into their lungs. Statins also reduced cell death from tetanus and group A streptococcus toxins. Tuomanen said scientists must still determine exactly how statins act to protect against toxins.

Other authors of this paper include Tamara Pestina, Yunming Hu and Derek Persons (St. Jude) and Angela Boyd and Ernesto Hinojosa (UTHSCSA).

The work was supported in part by the National Institutes of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, the National Institute on Aging and ALSAC.

Source: St. Jude Children’s Research Hospital


Children’s Genetic Disease Research Partnership

  • Author: Health Informer
  • Filed under: Health News
  • Date: Jan 20,2010

Dedicated to Saving Children’s Lives in CHASE COMMUNITY GIVING CHALLENGE

Parent Project Muscular Dystrophy together with Trisomy 18 Foundation are among 100 charities that earned a $25,000 grant during Round 1 of the Chase Community Giving Challenge on Facebook. Now in Round 2, Chase Bank has given them the opportunity to compete for an additional $1 Million prize and five $100,000 prizes, to be decided by public vote from January 15-22, 2010. Working together, these charities are advocating a novel approach to ask the Facebook public to support all charities with their votes that focus on saving children’s lives through funding of genetic disease research.

Parent Project Muscular Dystrophy’s Founding President and CEO Pat Furlong is thrilled to be part of this partnership. “As rare diseases, one of our biggest struggles as organizations is to raise awareness about our diseases. In the 16 years that PPMD has been fighting to end Duchenne muscular dystrophy, we, like the other members of this Partnership, have tried to reach as wide an audience as possible. This incredible contest provides us the largest awareness platform we have known and give us an opportunity to tell our families’ stories. By uniting as a Partnership, we are showing the Facebook community the importance of collaboration in advancing genetic research. Research that will save the lives of our children and our children’s children. A victory for any of us is a victory for all of us.”

“In the wake of the tragic earthquake in Haiti, we are all awakened to the fragility of life,” commented Victoria Miller, Executive Director of the Trisomy 18 Foundation. “The parents who are powering the activism in our Chase Campaign Partnership know this lesson and live it every day in battling for the lives of their children struggling against rare diseases. Every day we work hard through these organizations for more funding for more research. What unites us as Partners in this Chase Community Giving campaign is that we have a common need for more collaborative genetic research that accelerates the translation of science into treatments that will save all our children’s lives. And that takes awareness and activism and dollars and a bigger vision than one disease at a time. The advances in any one disease can literally transform the science for us all, and that’s why we know our causes are united. “

The Partnership has a simple goal — to advocate for the funding of Children’s Genetic Disease Research advanced through the Chase Community Giving contest. All Facebook users have an incredible opportunity to use their 5 votes for 5 Children’s Genetic Disease Research Charities in Round 2 of the Contest now through Midnight ET Friday evening, Jan 22nd.

Those 5 charities are:
– Parent Project Muscular Dystrophy at http://www.parentprojectmd.org/
– Trisomy 18 Foundation at http://www.trisomy18.org/
– Ehlers-Danlos Syndrome Network Cares at http://www.ehlersdanlosnetwork.org/
– For Spinal Muscular Atrophy: Gwendolyn Strong Foundation at http://gwendolynstrongfoundation.org/
– For Duchenne Muscular Dystrophy: Darius Goes West http://www.dariusgoeswest.org/

The public can also view a video about each charities “Big Idea” on Facebook at: http://apps.facebook.com/chasecommunitygiving.

Source: Parent Project Muscular Dystrophy


Study in Lancet Oncology is first to show the digene(R) HPV test has greater efficacy compared to Pap testing for preventing invasive cancers in developed countries, where cervical cancer screening is established and cancers are rare

Results from a study of more than 90,000 Italian women published by the Lancet Oncology found that testing for high-risk types of the human papillomavirus (HPV) DNA is significantly more effective in preventing invasive cervical cancer than cytology (Pap testing) alone. The trial used QIAGEN’s digene® HPV Test (also known as the digene® HC2 HPV DNA Test), which detects the high-risk types of HPV that can cause cervical cancer.

The New Technologies for Cervical Cancer (NTCC) study assessed the benefits and risks of shifting to HPV testing from standard cytology (Pap testing) in cervical cancer screening programs to increase effectiveness in preventing invasive cervical cancer.

“Our study is the first, to our knowledge, to show a greater efficacy for HPV testing versus cytology for preventing invasive cancers in a developed country, where cytological screening has been in place for years and advanced cervical cancers are extremely rare among screened women,” wrote study author Guglielmo Ronco and colleagues in the Unit for Cancer Epidemiology, Centro per la Prevenzione Oncologica in Turin, Italy. The NTCC study was conducted within organized screening programs with more than 70% of eligible women enrolled, which, according to study authors, suggests that “results are applicable to routine practice.” The study was released online in advance of publication on the Lancet Oncology Website.

The two-phase, randomized trial showed “a significantly lower number of cases in the HPV group versus the cytology group over the two screening rounds, indicating that the HPV-based screening is more effective than cytology in preventing cervical cancer,” wrote the study authors, who attributed the higher efficacy of HPV DNA testing to its earlier detection of clinically relevant lesions, which allowed for earlier treatment of precancers and prevention of invasive cancer. “For women aged 35 years or more, our results support the use of HPV DNA testing for primary screening at prolonged intervals, with cytology reserved for triage of HPV-positive women.”

“This study clearly demonstrates that a decrease in advanced cervical cancer is achievable – and hence lives saved – when HPV screening using the digene HPV Test is implemented, regardless of the region and level of cervical cancer prevention program in place,” said Peer Schatz, CEO of QIAGEN. “With cervical cancer prevention programs under evaluation by health ministries and government agencies across Europe and around the world to assess the most cost-effective strategies to protect women, this study could have significant implications. With our digene HPV test approved in the U.S. and Europe, and our careHPV test in development for use specifically in the developing world, we believe that regionally tailored cervical cancer prevention strategies that include HPV DNA testing can efficiently save millions of women’s lives.”

The NTCC study, which shows the ability of HPV testing to reduce invasive cervical cancer in an industrialized setting, complements an April 2009 study published in the New England Journal of Medicine demonstrating that in low-resource settings in rural India a single round of HPV testing significantly reduced the numbers of advanced cervical cancers and deaths, compared with other screening methods. Numerous studies of HPV testing have focused on clinical efficacy data and the high sensitivity of HPV testing to detection cervical lesions and cancers, while the NEJM and Lancet Oncology studies importantly show an actual reduction in the incidence of invasive cervical cancer.

NTCC Study Design and Results

In the NTCC study, two rounds of screening were performed in more than 90,000 women age 25-60. In phase one, women were randomly assigned to a control group with conventional cytology (Pap) only or to an intervention group where women had HPV DNA testing plus liquid-based cytology. In phase two, which was conducted two years later, with three to five years of follow-up, the control group received conventional cytology and the women in the intervention group received HPV testing alone.

In the first round of screening a comparable number of cancers were detected in each group (nine in the cytology group vs. seven in the HPV group). However, following the second phase conducted two years later, a significant decrease in cases of invasive cancer was detected in the HPV group (zero cases) compared with the cytology group (nine cases). After two screening rounds there was a significantly lower number of cases in the HPV group (7) versus the cytology group (18), indicating that HPV-based screening is more effective than cytology in preventing invasive cervical cancer. Also of note, a high proportion of cancers detected in the cytology group at the second round of screening were adenocarcinomas, which echo results reported in earlier studies that cytology is less effective in preventing adenocarcinoma than squamous-cell carcinoma.

“HPV-based screening is more effective than cytology in preventing invasive cervical cancer by detecting persistent high-grade lesions earlier and providing a longer low-risk period,” conclude the authors. An additional finding revealed that “detection of CIN2 was higher in the HPV than cytology group at round one, but only slightly lower at round two, suggesting that some regressive CIN2 lesions were identified and treated in young women.” CIN2 refers to potentially premalignant lesions, which in some cases are cleared by the body’s immune system before they become cancerous.

“HPV testing shows a great deal of promise to revolutionize cervical cancer screening,” wrote Dr. Philip Castle and Dr. Hormuzd Katki of the National Cancer Institute, who provide patient management recommendations in an accompanying editorial. “Data from the current study could be used to develop risk estimates to make the promise of more effective and cost-effective cervical cancer prevention a reality.”

Worldwide, cervical cancer affects approximately 500,000 women annually and is the second-most-common malignancy found in women. HPV testing identifies women with high-risk HPV infections that can cause cervical cancer, enabling diagnosis and treatment to be put in place before cervical cancer develops. The digene HPV Test is approved in the U.S. for use together with a Pap test (“co-testing”) in women 30 years and older, and as follow-up to inconclusive Pap test results (“ASCUS triage”). It is regarded as the “gold standard” in testing for high-risk types of HPV and is recommended in guidelines from leading U.S. medical organizations. In Europe, it is approved as an initial general population screening test either alone (“primary” or “frontline” screening) or together with a Pap test, as well as for ASCUS triage. The performance of the digene HPV Test has been published in more than 300 peer-reviewed journal articles and studied in clinical trials involving more than a million women worldwide. More than 40 million tests for carcinogenic HPV have been performed with the digene HPV Test. For more information, visit www.theHPVtest.com.

Source: QIAGEN


Brain fitness predicts crash risk

Brain training cuts crash risk of older drivers in half

Performance at simple mental tasks is highly predictive of crash risk and a small amount of cognitive training can cut the crash risk of older drivers in half, according to research presented this week at the 2010 annual meeting of the Transportation Research Board of the National Academy of Sciences.

This year, the age wave of 70 million baby boomers begins to join the ranks of some 39 million drivers already over age 65. Over time, older drivers tend to reduce their driving, but they still have a crash rate that is the highest of any age group, other than teenagers. Older drivers have the highest fatality rate from automobile crashes of all age groups. Yet, in our society “hanging up the keys” can be devastating and can lead to higher incidence of illness and death.

Three researchers presented findings that indicate that the crash risk of older drivers can be more accurately predicted, that it can be cut in half, and that older drivers can extend their period of safe driving.

Dr. Sam Chan of Posit Science presented data from a field trial with auto insurer Allstate involving 4,036 policyholders over age 50. It showed that poor performance in brief computerized cognitive tasks (involving speed of processing, useful field of view and divided attention) was highly predictive of the three-year crash history of drivers.

Dr. Karlene Ball of the University of Alabama presented data from a randomized controlled trial of 2,812 people over age 65 showing that a computerized cognitive training program could cut at-fault crash risk in half after just 10 hours of training. The training also improves reaction time, increases stopping distance by 22 feet, and reducing dangerous driving maneuvers.

Dr. Jerri Edwards of the University of South Florida presented data showing that morbidity increases after driving cessation, independent of health condition. She also showed that the cognitive training program reduced driving cessation risk of those trained by 40 percent, allowing them to keep driving safely, longer.

The computerized assessments and exercises were developed and measured over the past decade with funding from the National Institutes of Health. They are now commercially available to the general public for the first time in a software product called DriveSharp.

DriveSharp is recommended by the AAA Foundation for Traffic Safety. It retails for $89 and is available to AAA members for $79 through AAA clubs.

Source: Posit Science


Categories

Archives

Blogroll

Meta