Novel Mechanism Revealed For Increasing Recombinant Protein Yield In Tobacco

Elastin-like polypeptides (ELPs) cause plants to store GM proteins in special ‘protein bodies’, insulating them from normal cellular degradation processes and increasing the overall protein yield. Researchers writing in the open access journal BMC Biology have visualised the mechanism by which the synthetic biopolymer increases the accumulation of recombinant proteins.

Rima Menassa worked with a team of researchers from Agriculture and Agri-Food Canada in London, Ontario, to develop and test the ELP tags by targeting an ELP-green fluorescent protein (GFP) fusion to various organelles in the leaves of the tobacco plant. Tobacco is well-suited as a production system for recombinant proteins but the mechanism by which ELP fusions increase production yields in transgenic tobacco leaves was previously unknown. Menassa said, “ELP was shown to almost double the yield of GFP to 11% of total soluble protein when hyperexpressed in the endoplasmic reticulum (ER)”.

Based on their confocal and electron microscopy analyses, the researchers suggest that ELP fusions targeted to the ER induce the formation of novel mobile protein body-like structures in leaves, which appear similar in size and morphology to the prolamin-based protein bodies naturally found in plant seeds. These bodies may be responsible for ELP’s positive effect on recombinant protein accumulation by excluding the heterologous protein from normal physiological turnover.

The researchers targeted their ELP fusions to the cytoplasm, chloroplasts, apoplast and ER in Nicotiana benthamiana tobacco plants. They found that the ER was the only intracellular compartment in which the ELP significantly enhanced recombinant protein accumulation. They conclude, “An ER-targeted ELP fusion approach provides an effective strategy for depositing large amounts of concentrated heterologous protein within the limited space of the cell”.

Induction of protein body formation in plant leaves by elastin-like polypeptide fusions
Andrew J Conley, Jussi J Joensuu, Rima Menassa and Jim E Brandle
BMC Biology (in press)

Graeme Baldwin

BioMed Central

Smoking, Eating And Thinking: New Research On The Brain, Hormones, And Behavior

Certain hormones may make it more difficult for some to quit smoking, according to results of a study presented at the 6th International Congress of Neuroendocrinology (ICN 2006) in Pittsburgh inJune at the David L. Lawrence Convention Center. Other research reported includes animal research indicating what may be responsible for that yen for sweets.

Following are summaries of the studies’ findings and one giving perspective on the use of estrogen therapy for improving memory and brain power in women during menopause.

Hormones make it even harder for some to kick the habit If quitting smoking weren’t already hard enough, researchers are now saying that for some, kicking the habit may be even more difficult due to changes in levels of certain stress hormones.

Prior studies led researchers to believe that cortisol, a stress hormone that can contribute to depression, may make quitting more of a challenge. However, a Yale University School of Medicine study has found that cortisol levels alone may not be as useful for predicting the ability to quit as the ratio of DHEA (another stress hormone) to cortisol. Indeed, research has shown that DHEA may protect the brain against some potential deleterious effects of cortisol. Participants who relapsed eight days after abstinence from cigarettes were more likely to have a drop in the ratio between DHEA and cortisol as measured in their plasma than smokers able to maintain abstinence. According to lead researcher Ann Rasmusson, M.D., director of the neuroendocrine laboratory in Yale’s department of psychiatry, this finding indicates that the DHEA/cortisol ratio may prove to be a useful diagnostic tool for determining who is likely to have a more difficult time kicking the habit and also may serve as a potential target for smoking cessation treatment interventions.

One lump or two? Oxytocin influences a sweet tooth We all have weaknesses for certain kinds of food. Some of us can’t refuse a second helping of cake, while others can’t stay away from the chips and dip. It’s not merely a lack of willpower that leads us to indulge in our “trigger” foods, either. Research by Janet Amico, M.D., professor of medicine and pharmaceutical sciences, University of Pittsburgh schools of Medicine and Pharmacy, Regis Vollmer, Ph.D., professor of pharmaceutical sciences, School of Pharmacy, and colleagues, identified an oxytocin deficiency as a contributing factor in developing a sweet tooth. In more recent studies, Dr. Amico and her team sought to determine if the same hormone that fosters a hankering for sweets leads to a love affair with fatty snacks, as well. Results suggest that oxytocin may be to blame for sugar cravings, but that influence does not appear to extend to the desire of fatty foods.

In the study, Dr. Amico’s team compared two groups of mice – normal animals and those without the ability to produce oxytocin – to see if they had particular preference for drinking solutions with either added sugar or fat. While the oxytocin-deficient mice showed markedly greater intake of the sugar solution than their wild-type counterparts, both groups seemed to like the fat-enhanced drink just the same. Oxytocin is a hormone that plays a role in physical and emotional responses, induces labor, encourages maternal behavior and promotes positive relationship interactions. This work establishes a new role for oxytocin in influencing food tastes and limiting intake of sweets. Whether oxytocin also plays this same role in humans is not yet known, but the investigators hope to extend these studies to people. Perhaps abnormalities in the production of oxytocin may lead to excessive ingestion of sweet-tasting substances in humans.

Confused at Midlife: Clear Thinking About Estrogen Therapy and the Menopausal Brain While normal aging itself can result in a decline of certain cognitive abilities, many women at midlife complain specifically of difficulties in maintaining focus and concentration – of feeling wooly-headed. But even those with younger and sharper minds are finding the information about estrogen therapy confusing.

Some studies on hormone therapy indicate that estrogen supplementation can help boost brain power during the menopausal transition, when some aspects of cognition, particularly verbal memory, may begin to deteriorate. Other studies, particularly the Women’s Health Initiative Memory Study (WHIMS) published in 2004, find no benefit – and even some risk – associated with hormone replacement therapy. A large randomized controlled trial of more than 7,000 women, WHIMS found that estrogen fails to protect against cognitive aging in women who begin treatment after age 65. While these sets of findings appear to be at odds with one another, taken together, they indicate that estrogen supplementation can have the greatest benefit if begun during a woman’s transition into menopause – generally between the ages of 45 and 55 – rather than years after menstruation ceases. According to Barbara B. Sherwin, Ph.D., James McGill Professor of Psychology at McGill University in Montreal, this so-called “critical period hypothesis” is taking hold and is supported by a body of research that includes basic science, small animal, primate as well as human studies.

Held in a different part of the world every four years under the auspices of the International Neuroendocrine Federation, this year’s congress – Bridging Neuroscience and Endocrinology – is being sponsored by the American Neuroendocrine Society and the University of Pittsburgh School of Medicine. The first full day of the program, June 20, is being held in conjunction with the 10th Annual Meeting of the Society for Behavioral Neuroendocrinology.


Formerly the International Society of Neuroendocrinology, the International Neuroendocrine Federation consists of six member societies and seven regional groups, representing all parts of the world. The federation’s president is John A. Russell, MBChB, Ph.D., chair of neuroendocrinology, University of Edinburgh. The chair of the ICN 2006 scientific program is Iain J. Clarke, Ph.D., professorial fellow in the department of physiology at Monash University in Australia. Tony Plant, Ph.D., professor of cell biology and physiology and director of the Center for Research in Reproductive Physiology, University of Pittsburgh School of Medicine, is chair of the local organizing committee.

Lisa Rossi

Jocelyn Uhl Duffy

University of Pittsburgh Medical Center

US Government Fights Tuberculosis Via Dutch KNCV Tuberculosis Foundation

In the coming five years the United States Agency for International Development (USAID) will increase its contribution to the international fight against tuberculosis. This will be carried out via an international partnership with the KNCV Tuberculosis Foundation as the main contractor.

This new contract, called TB CARE, continues the successful international partnership between USAID and KNCV Tuberculosis Foundation along with its seven international partner organizations. The coming five years they will combine their efforts in this program through the Tuberculosis Coalition for Technical Assistance (TBCTA). While five years ago USAID reserved 150 million US Dollar for the five year program implemented with KNCV Tuberculosis Foundation, this amount is now increased to a maximum of 225 million US Dollar. The worldwide knowledge and support network of TBCTA will strengthen national TB control programs in different countries in Africa, Asia, Eastern Europe / Central Asian Republics, and Latin America.

The new investments are much needed. Worldwide, more than nine million people get infected with tuberculosis annually, of which almost two million die. KNCV Tuberculosis Foundation is worried about the stagnating detection rate and treatment of multi-drug resistant tuberculosis (MDR-TB).

The new five year project grant from USAID makes possible great strides forward in TB control globally. USAID offers KNCV Tuberculosis Foundation and its partners the task of broadening and strengthening the so-called “Stop TB Strategy”: the strategy officially acknowledged by the World Health Organization (WHO) for large-scale TB control. >From the start, KNCV Tuberculosis Foundation has aided in the development and application of this method. The program will also focus on the further development of the eradication of MDR-TB and the double infection of tuberculosis and HIV/AIDS. Finally, the strengthening of health systems will form an important part of the program.

TBCTA will offer practical support to support the national tuberculosis control programs in the hardest-hit countries in Africa, Asia, Eastern Europe / Central Asian Republics, and Latin America. The results aimed for in these countries include:

- The successful treatment of 3.6 million new TB cases;

- The detection and treatment of 90 thousand MDR-TB patients;

- To bring the mortality rate of new TB patients with HIV/AIDS under 10 percent;

- To ensure that tuberculosis has high priority within national health systems.


KNCV Tuberculosis Foundation

1957-58 Flu Pandemic Can Provide Clues To Planning For H1N1

As the U.S. prepares for a resurgence of H1N1 influenza this fall, much can be learned from looking at a previous pandemic that had similar patterns. In an article published today in Biosecurity and Bioterrorism, researchers at the Center for Biosecurity of the University of Pittsburgh Medical Center (UPMC) examined historical documents, published material, and newspaper coverage related to the 1957-58 influenza pandemic to compare the progress and severity of that outbreak with the current one. The simple, practical actions taken in 1957 allowed the country to continue functioning with minimal disruption.

Lead author Dr. D. A. Henderson had major responsibility for establishing the CDC influenza surveillance program during the early stages of the 1957 flu; data and analysis of events presented are based on his direct experiences as well as copies of surveillance reports that were published in 1957-58.

“There is need for an understanding in national policy circles of the options for dealing with a pandemic, and time is short if states and local communities are going to be prepared,” said Henderson.

During the 1957 pandemic, 25% of the U.S. population became ill, and excess mortality due to pneumonia and influenza occurred. It was a rapidly spreading disease, and it quickly became apparent to U.S. health officials that efforts to stop or slow its spread were futile.

Thus, no efforts were made to quarantine individuals or groups, and a deliberate decision was made not to cancel or postpone large meetings such as conferences, church gatherings, or athletic events. Health officials emphasized providing medical care to those who were sick and keeping community and health services functioning. School absenteeism was high, but schools were not closed unless the number of students or teachers fell low enough to warrant closure.

Special efforts were made to speed the production of vaccine, but the quantities that were produced were too late to substantially affect the impact of the epidemic. The spread of the disease was so rapid that within 3 months it had swept across the country and had largely disappeared.

Although it is impossible to predict the course that H1N1 will take, planning for it can be informed by the experiences of the recent past.

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, a quarterly peer-reviewed journal, is published by Mary Ann Liebert, Inc..

The Center for Biosecurity is an independent, nonprofit organization of the University of Pittsburgh Medical Center (UPMC) whose mission is to strengthen national security by reducing the risks posed by biological attacks, epidemics, and other destabilizing events, and to improve the nation’s resilience in the face of such events..

Source: Center for Biosecurity of UPMC

Smoking, some statistics

Smokers in their 30s and 40s are five times more likely to have a heart attack as nonsmokers of the same age, says WHO.
{Washington Post Health, June 26, 1997}

The addiction to smoking gives a 50% chance of killing the user: three times the risk of playing Russian roulette.
{ASH – Jan./Feb. 2000}

Tobacco is a mood-altering, addictive drug that kills 500,000 Americans (200 million worldwide) and costs $400 billion each year, according to “Smoking and Health Review,” (1992). We are told by the American Lung Association that tobacco contains more than 4,000 chemicals, 60 of which cause cancer. Some of the ‘killers’ are radioactivity, arsenic, ammonia, lead, formaldehyde, nitrogen dioxide, cadmium, phenol, benzene and hydrogen cyanide (the ‘gas chamber’ gas that poisons the respiratory enzymes).

Although smoking is a constant and chronic irritant to the body tissues, it is also a high-priced addictive pleasure (and sometimes displeasure) that is costly, not only in dollars but lives as well. In the U.S. alone, cigarette smoking causes over 1,000 deaths a day or a half-a-million lives a year, is responsible for 25% of the cancer deaths, and 30 to 40% of coronary heart disease. Smoking decreases life expectancy for all age groups, and for those who must breathe the passive smoke. There are 4,000 chemicals (lead, cyanide, arsenic, etc.) in cigarette smoke and over 30 of them carcinogenic. The act of smoking desensitizes the smoker to outside stimuli, and it is estimated that a smoker costs an employer about $5,000 yearly.

Smoking has about a 50% chance of killing the smoker. This is three times the risk of playing a round of Russian roulette.
{“How YOU Pay The Price,” ASH Smoking and Health Review, Jan./Feb. 2000}

WHO estimates that smoking kills more than four million people a year, This figure may rise to 10 million per year by 2030 because of surging tobacco use in developing countries.
{AP, “WHO accuses tobacco companies,” HealthCentral – Aug. 2000}

At least 625,000 individuals in the Americas die each year from tobacco use, according to the Pan American Health Organization (PAHO). Tobacco use seems to be on the rise in most countries in the Americas. What is needed is for governments to implement the recommendations of a report of the World Bank that was released last year. Ways to reduce tobacco use: increase taxes, restrict advertising, restricting smoking indoors, and strong, meaningful, and visible warnings on cigarette packages.
{“Tobacco kills 625,000 in the Americas each year.” Reuters Sept. 2000}


Patient Receives City Of Hope’s 10,000th Bone Marrow Transplant And Celebrates A Second Chance At Life

As stem cells from an anonymous volunteer donor began to restore life to William Fuller, who received City of Hope’s 10,000th bone marrow transplant on Jan. 13, 2011, his nurse wished him “Happy Birthday,” signaling the beginning of his new life. This week Fuller achieved another major milestone in his battle against cancer, being released from the hospital that has been his home for almost a month. Fuller, his doctors, and his sister met with reporters at City of Hope Helford Clinical Research Hospital to mark the occasion.

“I am very humbled by this experience,” Fuller told reporters. “Being able to stand here is living proof that this system of medicine does work. It’s a testament to a lot of hard work and research. I want to especially say thank you to my donor, who made a selfless choice to help a stranger. Someday I hope to meet him, and shake hands and say ‘thank you.’”

Bone marrow or stem cell transplantation – collectively known as hematopoietic cell transplantation (HCT) – is a complex, lifesaving procedure in which stem cells are used to help cure patients of their cancer. City of Hope helped pioneer this specialty, performing one of the nation’s first bone marrow transplants nearly 35 years ago. Since then, City of Hope has helped transplantation evolve into the gold standard for treating diseases such as leukemia, lymphoma and myeloma. Each year, the institution performs more than 500 transplants.

“Mr. Fuller is the poster child for what we do,” said Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and chair of the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope. “There are thousands of other people like him who have been helped because a donor came forward to provide lifesaving stem cells that allowed us to do a transplant and hopefully cure the disease. Every patient who gets through a transplant here is the beneficiary of a lot of laboratory work and hard thinking that’s gone into trying to solve the problem – how to best cure the cancer in the safest way possible.”

Born in Belize, Fuller came to Los Angeles in 1982, and eventually started a small home electronics repair business. In January 2008, the father of three began having night sweats, unrelenting fatigue and dropped 50 pounds. He was diagnosed with chronic myelogenous leukemia (CML) and eventually sought treatment at City of Hope. Although CML patients usually respond favorably to medications like Gleevec, these drugs often do not provide a lasting cure.

Fuller credited his sister, Karen Hyde, as being instrumental in arranging bone marrow drives in California, Florida and New York with the help of “Be the Match,” the national marrow donor program.

“When my brother was diagnosed he was told he had six to nine months to live,” said Hyde. “It hit me really hard. If something’s going to happen to him I’m going to fight and make sure I did everything I could.” She praised the “enormous outpouring” of people who came to the drives. “I encourage everyone who’s out there who’s looking for a donor to just keep on fighting.”

Fuller and Hyde knew finding a donor would be challenging given his mixed ancestry so their drives reached out to people of Belizean, Caribbean and Mayan descent. Remarkably, three donors with an exact genetic match were found and Fuller was transplanted Jan. 13 with lifesaving cells from one of them.

Forman said that many of his patients view their donors as new members of their family, and often develop lifelong relationships.

“They are ‘blood relatives,’” he said.


City of Hope

View drug information on Gleevec.

New Report Underlines Need For Congress To Give FDA Authority Over Tobacco Products, USA

A new report from the President’s Cancer Panel reinforces the urgent need for Congress to pass legislation giving the U.S. Food and Drug Administration (FDA) authority over tobacco. The report, Promoting Healthy Lifestyles: Policy, Program, and Personal Recommendations for Reducing Cancer Risk, states that FDA should have the crucial authority to regulate this product to reduce the deadly toll of tobacco.

The panel, chaired by LaSalle D. Leffall, Jr., M.D., F.A.C.S. of Howard University College of Medicine and whose members included Lance Armstrong, Founder of the Lance Armstrong Foundation and Margaret L. Kripke, Ph.D. from The University of Texas M.D. Anderson Cancer Center, urges “the leadership of this nation to summon the political will” to address the public health crisis caused by tobacco use. Each year, more than 438,000 Americans die from tobacco-caused diseases, including lung cancer and chronic obstructive pulmonary disease, also known as COPD, which includes chronic bronchitis and emphysema.

Currently, identical bipartisan bills are pending in the U.S. Senate (S. 625) and House of Representatives (H.R. 1108) that would give FDA authority over tobacco products. Fifty-three Senators and nearly 200 members of the House of Representatives have cosponsored the legislation. On August 1st, the Senate’s Health, Education, Labor and Pensions Committee voted to send the legislation to the full Senate for action. We are hopeful that the House of Representatives will begin their work on the legislation in September.

The panel makes clear that states also have important responsibilities, including funding tobacco control programs at levels recommended by the Centers for Disease Control and Prevention, passing comprehensive smokefree workplace legislation, and increasing tobacco taxes. The report references the American Lung Association’s Smokefree Air 2010 Challenge, which calls on states to pass legislation making all public places and workplaces 100 percent smokefree by 2010.

Finally, the panel recommends that Congress increase the federal excise tax on tobacco products. Currently, bills are pending in both the Senate and House that would increase the federal excise tax on cigarettes by 61 cents and 45 cents, respectively, to fund the State Children’s Health Insurance Program (SCHIP).

About the American Lung Association

Beginning our second century, the American Lung Association is the leading organization working to prevent lung disease and promote lung health. Lung disease death rates continue to increase while other leading causes of death have declined. The American Lung Association funds vital research on the causes of and treatments for lung disease. With the generous support of the public, the American Lung Association is “Improving life, one breath at a time.”


An Apple A Day Keeps The Grim Reaper Away

Scientists are reporting the first evidence that consumption of a healthful antioxidant substance in apples extends the average lifespan of test animals, and does so by 10 percent. The new results, obtained with fruit flies – stand-ins for humans in hundreds of research projects each year – bolster similar findings on apple antioxidants in other animal tests. The study appears in ACS’s Journal of Agricultural and Food Chemistry.

Zhen-Yu Chen and colleagues note that damaging substances generated in the body, termed free radicals, cause undesirable changes believed to be involved in the aging process and some diseases. Substances known as antioxidants can combat this damage. Fruits and vegetables in the diet, especially brightly colored foods like tomatoes, broccoli, blueberries, and apples are excellent sources of antioxidants. A previous study with other test animals hinted that an apple antioxidant could extend average lifespan. In the current report, the researchers studied whether different apple antioxidants, known as polyphenols, could do the same thing in fruit flies.

The researchers found that apple polyphenols not only prolonged the average lifespan of fruit flies but helped preserve their ability to walk, climb and move about. In addition, apple polyphenols reversed the levels of various biochemical substances found in older fruit flies and used as markers for age-related deterioration and approaching death. Chen and colleagues note that the results support those from other studies, including one in which women who often ate apples had a 13-22 percent decrease in the risk of heart disease, and polish the apple’s popular culture image as a healthy food.

ARTICLE: “Apple Polyphenols Extend the Mean Lifespan of Drosophila melanogaster”

American Chemical Society

Also In Global Health News: Smoking In China; Concurrent Partnerships And HIV; Farming In Rwanda

New Data Shows China’s ‘Tobacco Addiction,’ WHO Says

“Over half of China’s men smoke,” the Wall Street Journal’s “China RealTime Report” blog reports, in an article that examines Beijing’s “most critical look yet at its national smoking habit.” The statistics “are contained in a newly released Global Adult Tobacco Survey,” which included people across the country and was supported by the WHO. The data also show that “less than a quarter – smoker or not – think smoking causes diseases like lung cancer” (Areddy, 8/17). Agence France-Presse adds that “[a]uthorities have pledged to ban smoking in all indoor, public places by next year, but activists and experts have raised doubts that the rules can be implemented in a country where law enforcement is weak.” The article also includes comments from WHO China head Michael O’Leary who said the country’s “tobacco addiction deserves the same level of concern as an outbreak of SARS or H1N1″ (8/17).

Concurrent Partnerships Examined In African Study

“In one of the first studies to investigate multiple concurrent partnerships (MCPs) among African [men who have sex with men] MSM, just over half of the 537 men surveyed in Malawi, Namibia and Botswana reported that they had had sex with both men and women in the last six months, and about a third of these men reported that the relationships had been concurrent,” IRIN/PlusNews reports, also noting that “MCPs have been identified as a main driver of the HIV epidemic in southern Africa.” Gift Trapence of Malawi’s Centre for the Development of People said, “[T]hese issues have never been involved in our HIV prevention work … When we try to design these programmes, we need to look at all the sexual behaviours [of men].” According to IRIN/PlusNews, he also “said a larger, population-based study was planned to explore the findings” (8/16).

Small-Scale Rwandan Farmers Benefit From Agricultural Research

Inter Press Service reports on efforts to improve the lives of farmers in Rwanda. Specifically, the article examines the work of Joelle Nsamira Kajuga of the Rwanda Institute of Agricultural Research, who “leads a team of researchers studying modified and improved seed to assess how small-scale farmers in the remote rural areas of Rwanda could adopt this seed, along with new agriculture practices, to increase their productivity.” Kajuga told IPS that farmers should be trained in using improved seed and managing disease. The article also includes comments from two small-scale farmers, including one who “was able to effectively use research to increase her crop production” (Twahirwa, 8/16).

This information was reprinted from globalhealth.kff with kind permission from the Henry J. Kaiser Family Foundation. You can view the entire Kaiser Daily Global Health Policy Report, search the archives and sign up for email delivery at globalhealth.kff.

© Henry J. Kaiser Family Foundation. All rights reserved.

First Time A Statin’s Kidney Benefits Linked To Reduced Cardiovascular Events

Improvements in kidney function in patients treated with Lipitor® (atorvastatin calcium) were shown to strongly correlate with a reduced risk of major cardiovascular events in patients with pre-existing cardiovascular disease, according to a post hoc sub-analysis of the five-year Treating to New Targets (TNT) study presented today at the Annual Scientific Sessions of the American Heart Association.

“This is the first time for any statin that an association between improvements in kidney function and a reduction in cardiovascular events has been shown,” said Dr. James Shepherd, clinical academic consultant, department of pathological biochemistry, University of Glasgow Medical School, and lead investigator of the analysis. “This is important for patients, since studies have shown that people with high cholesterol have a more rapid decrease in kidney function over time and that chronic kidney disease is more frequent in patients with cardiovascular disease.”

In this new post hoc analysis, kidney function was assessed using estimated glomerular filtration rate (eGFR), as recommended by the National Kidney Foundation. Increases in eGFR indicate improved kidney function.

Lipitor has previously been shown to provide dose-dependent increases in eGFR in heart disease patients. Findings from this new analysis showed that in patients with heart disease treated with Lipitor, for each 1 mL/min/1.73 m2 increase in eGFR there was a 2.7 percent relative reduction in risk of major cardiovascular events. Similar risk reductions per 1 mL/min/1.73 m2 increase in eGFR were observed for secondary endpoints such as major coronary events, nonfatal heart attack and fatal or nonfatal stroke.

“This analysis is exciting because it suggests a potential additional benefit of Lipitor — improving kidney function while reducing cardiovascular events,” said Dr. Rochelle Chaiken, vice president of Pfizer’s cardiovascular and metabolic medical division.

Throughout the TNT study, both doses of Lipitor (10 and 80 mg) were generally well-tolerated.

About the TNT Study

The TNT study was an investigator-led trial coordinated by an independent steering committee and funded by Pfizer. The study enrolled 10,001 men and women with coronary heart disease aged 35 years to 75 years in 14 countries and followed them for an average of five years. Primary study results were published in The New England Journal of Medicine in 2005.

The primary endpoint of the original TNT study was the occurrence of a first major cardiovascular event, defined as death from heart disease, non-fatal heart attacks, resuscitated cardiac arrest, or fatal or non-fatal strokes.

Lipitor 80 mg is not a starting dose. Lipitor is not approved in all countries to reduce the risk of cardiovascular events in patients with existing heart disease.

Important U.S. Prescribing Information

Lipitor is a prescription medication. It is used in patients with multiple risk factors for heart disease such as family history, high blood pressure, age, low HDL (“good” cholesterol) or smoking to reduce the risk of a heart attack and stroke, certain kinds of heart surgery and chest pain. Lipitor is also used in patients with type 2 diabetes and at least one other risk factor for heart disease such as high blood pressure, smoking or complications of diabetes, including eye disease and protein in urine, to reduce the risk of heart attack and stroke.

Lipitor is used in patients with existing coronary heart disease to reduce the risk of heart attack, stroke, certain kinds of heart surgery, hospitalization for heart failure, and chest pain.

When diet and exercise alone are not enough, Lipitor is used along with a low-fat diet and exercise to lower cholesterol.

Lipitor is not for everyone. It is not for those with liver problems. And it is not for women who are nursing, pregnant or may become pregnant.

Patients taking Lipitor should tell their doctors if they feel any new muscle pain or weakness. This could be a sign of rare but serious muscle side effects. Patients should tell their doctors about all medications they take. This may help avoid serious drug interactions. Doctors should do blood tests to check liver function before and during treatment and may adjust the dose. The most common side effects are gas, constipation, stomach pain and heartburn. They tend to be mild and often go away.