Running Five Minutes a Day May Reduce Risk of Cardiovascular Disease

Running for only a few minutes a day or at slow speeds may significantly reduce a person’s risk of death from cardiovascular disease compared to someone who does not run, according to a study published today in the Journal of the American College of Cardiology.

JACC

Exercise is well-established as way to prevent heart disease and it is component of an overall healthy life, but it is unclear whether there are health benefits below the level of 75 minutes per week of vigorous-intensity activity, such as running, recommended by the U.S. government and World Health Organization.

Researchers studied 55,137 adults between the ages of 18 and 100 over a 15-year period to determine whether there is a relationship between running and longevity. Data was drawn from the Aerobics Center Longitudinal Study, where participants were asked to complete a questionnaire about their running habits. In the study period, 3,413 participants died, including 1,217 whose deaths were related to cardiovascular disease. In this population, 24 percent of the participants reported running as part of their leisure-time exercise.

Compared with non-runners, the runners had a 30 percent lower risk of death from all causes and a 45 percent lower risk of death from heart disease or stroke. Runners on average lived three years longer compared to non-runners. Also, to reduce mortality risk at a population level from a public health perspective, the authors concluded that promoting running is as important as preventing smoking, obesity or hypertension. The benefits were the same no matter how long, far, frequently or fast participants reported running. Benefits were also the same regardless of sex, age, body mass index, health conditions, smoking status or alcohol use.

The study showed that participants who ran less than 51 minutes, fewer than 6 miles, slower than 6 miles per hour, or only one to two times per week had a lower risk of dying compared to those who did not run. DC (Duck-chul) Lee, Ph.D., lead author of the study and an assistant professor in the Iowa State University Kinesiology Department in Ames, Iowa, said they found that runners who ran less than an hour per week have the same mortality benefits compared to runners who ran more than three hours per week. Thus, it is possible that the more may not be the better in relation to running and longevity.

Researchers also looked at running behavior patterns and found that those who persistently ran over a period of six years on average had the most significant benefits, with a 29 percent lower risk of death for any reason and 50 percent lower risk of death from heart disease or stroke.

“Since time is one of the strongest barriers to participate in physical activity, the study may motivate more people to start running and continue to run as an attainable health goal for mortality benefits,” Lee said. “Running may be a better exercise option than more moderate intensity exercises for healthy but sedentary people since it produces similar, if not greater, mortality benefits in five to 10 minutes compared to the 15 to 20 minutes per day of moderate intensity activity that many find too time consuming.”

- MFP News Services
- 1/13/15

New Treatment May Benefit Patients With Certain Lung Cancer Inhibitors

PHILADELPHIA — A combination of the EGFR-targeted anticancer therapeutics afatinib (Gilotrif) and cetuximab (Erbitux) yielded clinical responses in 29 percent of patients who had lung cancer harboring epidermal growth factor receptor (EGFR) mutations that had stopped responding to the EGFR inhibitors erlotinib (Tarceva) and gefitinb (Iressa), according to data from a phase Ib clinical trial published in Cancer Discovery, a journal of the American Association for Cancer Research.

“Treatment with erlotinib and gefitinib leads to dramatic tumor regression and has improved survival for patients with EGFR-mutant lung adenocarcinoma,” said Yelena Y. Janjigian, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center in New York, and assistant professor of medicine at Weill Cornell Medical College in New York. “Unfortunately, these cancers invariably acquire resistance to these drugs and the patient’s disease progresses. There are currently no effective therapies for patients in this situation.”

Weill Cornell Medical College

Each year, nearly 20,000 people in the United States are diagnosed with lung adenocarcinomas that harbor EGFR mutations. Mutations in the EGFR tyrosine kinase domain result in aberrant activation of the protein kinase enabling the cancer cells’ signaling.

“Our study shows that a combination of afatinib and cetuximab can yield durable and robust clinical responses in the setting of acquired resistance, although larger, randomized trials are needed to confirm the results,” Janjigian continued. “Importantly, the afatinib/cetuximab combination benefited patients whether or not their cancer had acquired resistance to erlotinib or gefitinb as a result of a secondary mutation in EGFR called T790M.”

Of the 201 patients enrolled in the clinical trial by Janjigian and colleagues, 126 received the maximum-tolerated dose of combined afatinib and cetuximab. All these patients had EGFR-mutant lung cancer that had progressed during treatment with erlotinib or gefitinib, and 37 of them had a confirmed objective response to afatinib plus cetuximab. The overall median duration of the responses was 5.7 months.

Among the 37 patients who had a confirmed objective response, 22 had their tumors shrink by 50 percent or more. According to Janjigian, this level of tumor shrinkage is clinically significant as it results in regression of cancer-related symptoms and improvement in the patient’s quality of life.

One of the most common causes of resistance to erlotinib or gefitinib is that the tumors acquire the EGFR T790M mutation. In the study, the objective response rates were not statistically different for patients with and without the EGFR T790M mutation in their tumors: 32 and 25 percent, respectively. The median durations of the responses were 5.6 months for patients with EGFR T790M-positive tumors and 9.5 months for those with EGFR T790M-negative tumors.

“We were pleased to observe that EGFR T790M-positive and T790M-negative tumors responded,” said Janjigian. “This is important because there are third-generation EGFR inhibitors under development that can target EGFR T790M but it is not likely that these will benefit patients with EGFR T790M-negative disease.

“Another important point from our study is that it provides for the first time a clinical confirmation of a concept that has beencontroversialin the field: that a significant proportion of EGFR-mutant lung adenocarcinomas with acquired resistance to erlotinib and gefitinb are still dependent on EGFR signaling for their growth and survival,” Janjigian added.

-MFP News Services
-12/23/14

Disruptive Effects of Anesthesia on Brain Cell Connections Only Temporary

The study, published in a recent issue of the journal PLOS ONE, was conducted by biologists at the University of California, San Diego and Weill Cornell Medical College in New York in response to concerns, arising from multiple studies on humans over the past decade, that exposing children to general anesthetics may increase their susceptibility to long-term cognitive and behavioral deficits, such as learning disabilities.

University of California - San Diego - Biological Sciences

An estimated six million children, including 1.5 million infants, undergo surgery in the United States requiring general anesthesia each year and a least two large-scale clinical studies are now underway to determine the potential risks to children and adults.

“Since these procedures are unavoidable in most cases, it’s important to understand the mechanisms associated with the potentially toxic effects of anesthetics on the developing brain, and on the adult brain as well,” said Shelley Halpain, a professor of biology at UC San Diego and the Sanford Consortium for Regenerative Medicine, who co-headed the investigation. “Because the clinical studies haven’t been completed, preclinical studies, such as ours, are needed to define the effects of various anesthetics on brain structure and function.”

“There is concern now about cognitive dysfunction from surgery and anesthesia—how much these effects are either permanent or slowly reversible is very controversial,” said Hugh Hemmings, Jr., chair of anesthesiology at Weill Cornell and the study’s other senior author. “It has been suggested recently that some of the effects of anesthesia may be more lasting than previously thought. It is not clear whether the residual effects after an operation are due to the surgery itself, or the hospitalization and attendant trauma, medications and stress—or a combination of these issues.”

However, he added, “There is evidence that some of the delayed or persistent cognitive effects after surgery are not primarily due to anesthesia itself, but more importantly to brain inflammation resulting from the surgery. But this is not yet clear.”

The team of biologists examined one of the most commonly used general anesthetics, a derivative of ether called “isoflurane” used to maintain anesthesia during surgery.

“Previous studies in cultured neurons and in the intact brains of rodents provided evidence suggesting that exposure to anesthetics might render neurons more susceptible to cell death through a process called ‘apoptosis’,” said Halpain. “While overt cell death could certainly be one way to explain any long-lasting neurocognitive consequences of general anesthesia, we hypothesized that there could be other cellular mechanisms that disrupt neural circuits without inducing cell death per se.”

One such mechanism, she added, is known as “synaptotoxicity.” In this mechanism of neural-circuit disruption, the “synapses,” or junctions between neurons, become weakened or shrink away due to some factor that injures the neurons locally along their axons (the long processes of neurons that transmit signals) and dendrites (the threadlike extensions of neurons that receive nerve signals) without inducing the neurons themselves to die.

In the experiments at UC San Diego headed by Jimcy Platholi, a postdoctoral researcher in Halpain’s lab who is now at Weill Cornell, the scientists used neurons from embryonic rats taken from the hippocampus, a part of the mammalian forebrain essential for encoding newly acquired memories and ensuring that short-term memories are converted into long-term memories. The researchers cultured these brain cells in a laboratory dish for three weeks, allowing the neurons time to mature and to develop a dense network of synaptic connections and “dendritic spines”—specialized structures that protrude from the dendrites and are essential mediators of activity throughout neural networks.

“Evidence from animal studies indicates that new dendritic spines emerge and existing spines expand in size during learning and memory,” explained Halpain. “Therefore, the overall numbers and size of dendritic spines can profoundly impact the strength of neural networks. Since neural network activity underlies all brain function, changes in dendritic spine number and shape can influence cognition and behavior.”

Using neurons in culture, rather than intact animal brains, allowed the biologists to take images of the synapses at high spatial resolution using techniques called fluorescence light microscopy and confocal imaging. They also used time-lapse microscopy to observe structural changes in individual dendritic spines during exposure to isoflurane. Karl Herold, a research associate in the Hemmings laboratory and a co-author of the study, performed some of the image analysis.

“Imaging of human brain synapses at this level of detail is impossible with today’s technology and it remains very challenging even in laboratory rodents,” said Halpain. “It was important that we performed our study using rodent neurons in a culture dish, so that we could really drill down into the subcellular and molecular details of how anesthetics work.”

The researchers wondered whether brief exposure to isoflurane would alter the numbers and size of dendritic spines, so they applied the anesthetic to the cultured rat cells at concentrations and durations (up to 60 minutes) that are frequently used during surgery.

“We observed detectable decreases in dendritic spine numbers and shape within as little as 10 minutes,” said Halpain. “However this spine loss and shrinkage was reversible after the anesthetic was washed out of the culture.”

“Our study was reassuring in the sense that the effects are not irreversible and this fits in with known clinical effects,” said Hemmings. “For the most part, we find that the effects are reversible.”

“We clearly see an effect—a very marked effect on the dendritic spines—from use of this drug that was reversible, suggesting that it is not a toxic effect, but something more relevant to the pharmacological actions of the drug,” he added. “Connecting what we found to the cognitive effects of isoflurane will require much more detailed analysis.”

The team plans to follow up its study with future experiments to probe the molecular mechanisms and long-lasting consequences of isoflurane’s effects on neuron synapses and examine other commonly-used anesthetics for surgery.

- MFP News Services
- 12/8/14