Researchers at Stanford University School of Medicine have unearthed a connection between advancing age, systemic inflammation, cardiovascular disease and coffee consumption.

An extensive analysis of blood samples, survey data and medical and family histories obtained from more than 100 human participants has revealed a fundamental inflammatory mechanism associated with human aging and the chronic diseases that come with it.

The study indicates that metabolites, or breakdown products, of nucleic acids, which serve as building blocks for our genes, circulating in the blood can trigger the inflammatory process, which in turn can be a driver of cardiovascular disease and increased rates of mortality overall.

“More than 90 percent of all noncommunicable diseases of aging are associated with chronic inflammation,” said David Furman, a consulting associate professor at the Stanford Institute for Immunity, Transplantation and Infection and lead author of the study published online this week in Nature Medicine.

As shown by more than 1,000 papers, chronic inflammation contributes to many cancers, Alzheimer’s disease and other dementias, cardiovascular disease, osteoarthritis and even depression.

The multiyear study provides evidence that caffeine and its metabolites may counter the action of these circulating nucleic-acid metabolites, possibly explaining why coffee drinkers tend to live longer than abstainers.

“Many studies have shown this association,” Furman said. “We’ve found a possible reason for why this may be so.”

The researchers used data gathered from a long-term program begun 10 years ago by Mark Davis, a professor of microbiology and immunology and the director of the Stanford Institute for Immunity, Transplantation and Infection, and study co-author Cornelia Dekker, professor of pediatric infectious diseases, to study the immunology of aging. In that program, healthy participants ages 20-30 and another group older than 60 were monitored annually via surveys, blood draws and reviews of their medical histories.

For the new study, by zeroing in on two clusters of genes whose activity was associated with the production of a potent circulating inflammatory protein called IL-1-beta, the researchers compared blood drawn from older versus younger study participants to see which genes tended to be more highly activated in older people. The genes within each cluster appeared to work in coordination with one another.

The researchers found that incubating a type of immune cell with two of those nucleic-acid metabolites boosted activity in one of the gene clusters, resulting in increased IL-1-beta production. When injected into mice, the substances triggered massive systemic inflammation, along with high blood pressure. In addition, immune cells infiltrated and clogged the animals’ kidneys, increasing renal pressure substantially.

“Our findings show that an underlying inflammatory process, which is associated with aging, is not only driving cardiovascular disease but is, in turn, driven by molecular events that we may be able to target and combat,” Davis was quoted as saying in a news release from Stanford, which is located in Northern California on the U.S. west coast.

This inflammatory mechanism was found to be activated only in some, but not all, of the older study participants. Those in whom it was relatively quiescent tended to drink more caffeinated beverages. Laboratory experiments revealed that the mechanism was directly countered by caffeine and associated compounds.

Intrigued by the correlation between older participants’ health, gene-cluster activation and self-reported rates of caffeine consumption, the researchers followed up and verified that blood from the group with low cluster activity was enriched for caffeine and a number of its metabolites, compared with blood from the group with high cluster activity.

Examples of these metabolites are theophylline, also found in tea, and theobromine, which abounds in chocolate.

Incubating immune cells with caffeine and its breakdown products along with the inflammation-triggering nucleic acid metabolites substantially prevented the latter from exerting their powerful inflammatory effect on the cells.

“That something many people drink – and actually like to drink – might have a direct benefit came as a surprise to us,” said Davis, who noted that the study did not prove a causal link. “And we’ve shown more rigorously, in laboratory tests, a very plausible mechanism for why this might be so.”

source: Manila Bulletin

Chewing food properly is not just good for digestion, but can improve mouth’s immune system protecting you against illness, according to a study released Thursday by The University of Manchester.

Scientists have known that food nutrients can contribute to a healthy immune system in the mouth, but the study, led by researchers from The University of Manchester and National Institutes of Health in the United States, shows that chewing food also plays an important role.

The team found that when you are chewing, the action will stimulate a specific type of immune cell — the “Th17” cell.

In their experiment, the team changed the hardness of the food fed to mice, which caused more mastication. That stimulated the increases in Th17 cells in mice.

“The immune system performs a remarkable balancing act at barrier sites such as the skin, mouth and gut by fighting off harmful pathogens while tolerating the presence of normal friendly bacteria,” says one of the study authors Joanne Konkel from The University of Manchester.

“Our research shows that, unlike at other barriers, the mouth has a different way of stimulating Th17 cells: not by bacteria but by mastication. Therefore mastication can induce a protective immune response in our gums,” says Konkel.

However, it is not always good to have too many Th17 cells, which can lead to periodontitis.

Nonetheless, “because inflammation in the mouth is linked to development of diseases all around the body, understanding the tissue-specific factors that regulate immunity at the oral barrier could eventually lead to new ways to treat multiple inflammatory conditions,” adds Konkel.

source: Manila Bulletin

Women who eat a lot of grilled, smoked and barbecued meats and develop breast cancer may be more likely to die from their cancer than those who eat less of these foods, a U.S. study suggests.
A higher intake of barbecued, smoked or grilled meat before diagnosis was also associated with 23 percent higher odds of death from all causes, the study found.
Of the three cooking options, smoking may be the worst. Routinely eating smoked beef, lamb and pork was tied to a 17 percent greater risk of death from all causes and 23 percent higher odds of dying from breast cancer.
"There are many carcinogens found in grilled or smoked meats," said lead study author Humberto Parada, a researcher at the University of North Carolina at Chapel Hill. "One of the most common are polycyclic aromatic hydrocarbons (PAH), which are formed during combustion of organic material."
Women may be exposed to these carcinogens by cigarette smoke or air pollution, which are associated with an increased risk of developing breast cancer, Parada said by email. Some research has suggested exposure to these chemicals through grilled or smoked meat can increase the risk of breast cancer, but the current study offers some of the first evidence suggesting it also influences survival odds.
"Grilling or smoking meats produces PAHs much more readily than other cooking methods, such as pan-frying," Parada said. "Several factors may influence the formation of PAHs including ‘doneness’ and meat type - higher fat content may result in the formation of more PAHs."
For the current study, researchers interviewed 1,508 women diagnosed with breast cancer about their eating habits in 1996 or 1997 and then questioned them again five years later.
After following half of the women for at least 17.6 years, there were 597 deaths including 237 fatalities from breast cancer.
Compared to women who consistently ate only small amounts of grilled, barbecued or smoked meat, women who consumed a lot of these foods both before and after their diagnosis were 31 percent more likely to die during the study period, researchers report in the Journal of the National Cancer Institute.
Women who included poultry and fish in their diet before or after their breast cancer diagnosis were 45 percent less likely to die during the study than women who didn't eat these foods.
Lower levels of saturated fats in chicken and fish relative to red meats might help explain this, Dr. Pagona Lagiou, a researcher at the University of Athens Medical School in Greece who wasn't involved in the study, said by email.
It's also possible that chicken and fish have a protective effect because women eat less red meat, said Carrie Daniel-MacDougall, a researcher at the University of Texas MD Anderson Cancer Center in Houston who wasn't involved in the study.
"Simply increasing fish or poultry intake, without reducing red meat intake, is likely to be less beneficial for cancer prevention," Daniel-MacDougall added by email.
One limitation of the study is that it relied on women to report how often they consumed different foods and didn't assess portion sizes or the number of times they ate meats each week, the authors note. The study also isn't an experiment, so it cannot prove that different types of meat influence survival odds with breast cancer.
Still, the findings suggest women should pay attention to how they cook their food to minimize their exposure to carcinogenic chemicals, said Dr. Mingyang Song, a researcher at Massachusetts General Hospital in Boston and Harvard University who wasn't involved in the study.
"These chemicals can be produced from wood smoke or when fat and juices from meat grilled directly over an open fire drip onto the fire, creating flames and smoke," Song said by email. "Generally, the fattier the meat is, the higher the chemical levels will be."


Researchers with Oregon State University (OSU) have identified a molecule that neutralizes germs’ resistance to antibiotic.

Known as a PPMO, short for peptide-conjugated phosphorodiamidate morpholino oligomer, the molecule has shown ability to inhibit expression of an enzyme, known as NDM-1, short for New Delhi metallo-beta-lactamase, that makes bacteria resistant to a wide range of penicillins.

The study demonstrated that in vitro the new PPMO restored the ability of an ultra-broad-spectrum drug of the carbapenem class, called meropenem, to fight three different genera of bacteria that express NDM-1, and that a combination of the PPMO and meropenem was effective in treating mice infected with a pathogenic strain of E. coli that is NDM-1 positive.

“We’re targeting a resistance mechanism that’s shared by a whole bunch of pathogens,” Bruce Geller, professor of microbiology in OSU’s College of Science and College of Agricultural Sciences, was quoted as saying in a news release.

“It’s the same gene in different types of bacteria, so you only have to have one PPMO that’s effective for all of them, which is different than other PPMOs that are genus specific.”

While the results were published in the Journal of Antimicrobial Chemotherapy, Geller said the PPMO will likely be ready for testing in humans in about three years.

“We’ve lost the ability to use many of our mainstream antibiotics,” Geller explained. “Everything’s resistant to them now. That’s left us to try to develop new drugs to stay one step ahead of the bacteria, but the more we look the more we don’t find anything new. So that’s left us with making modifications to existing antibiotics, but as soon as you make a chemical change, the bugs mutate and now they’re resistant to the new, chemically modified antibiotic.”

That progression made the carbapenems, the most advanced penicillin-type antibiotic, the last line of defense against bacterial infection.

“The significance of NDM-1 is that it destroys carbapenems, so doctors have had to pull out an antibiotic, colistin, that hadn’t been used in decades because it’s toxic to the kidneys,” Geller said. “That is literally the last antibiotic that can be used on an NDM-1-expressing organism, and we now have bacteria that are completely resistant to all known antibiotics.”

Geller added: “but a PPMO can restore susceptibility to antibiotics that have already been approved, so we can get a PPMO approved and then go back and use these antibiotics that had become useless.”

source: Manila Bulletin

The worst form of drug-resistant tuberculosis isn't just arising from inadequate treatment, it's mostly being spread from person to person, according to a new study of hundreds of cases in South Africa that has important implications for how the deadly disease is treated.
Researchers tracked TB that is resistant to at least four key drugs and found that 69 percent of the victims had never received treatment, an indication that they had acquired it from others with extensively drug-resistant TB.
TB develops resistance to drugs when it is attacked with lackluster therapy, allowing the slow-growing bacterium to become insensitive to well-established therapies. Strains that are simultaneously resistant to at least four drugs have been reported in 105 countries.
"For many years, there was this thought that maybe drug-resistant TB strains might not be able to be transmitted as efficiently a regular TB strains," coauthor Dr. Neel R. Gandhi of Emory University’s Rollins School of Public Health in Atlanta told Reuters Health by phone.
The results published in the New England Journal of Medicine "turn this idea on its head," said Dr. William Schaffner, professor of infectious disease at Vanderbilt University Medical Center in Atlanta who was not involved in the research.
The study team's estimate that two thirds of the cases are surfacing because the disease is spreading by person-to-person contact "is mostly likely a minimum estimate," Gandhi said.
"This is an epidemic we've known about for 10 years and we don't seem to be making a dent in it," he said. "And that may be because the driver isn't what we thought it was."
"It raises the possibility of turning the clock back to the 1930s and 1940s" and requiring infected people to live in sanitariums so patients can't inadvertently spread the disease, Schaffner said. "You also have to do better at diagnosing them earlier. We're going to have to be a lot more aggressive in finding the infected people early. These are substantial public health challenges."
Drug resistance has gotten so bad, the rate of successful treatment can be less than 40 percent if a person acquires an extensively drug-resistant strain. It can be particularly deadly in people who also harbor HIV, the AIDS virus. In South Africa, where the new study was done, there has been a 10-fold increase in the number of extensively drug-resistant cases in the past decade. One in 36,000 are now infected.
The team of researchers used contact tracing to find where the TB patients were spending at least two hours per week, trying to uncover any links.
They found 31 clusters of the disease, the largest of which accounted for 84 percent of the 404 patients they studied.
Living with someone with TB accounted for most of the acquired cases, although the disease was also spread in the workplace (representing 13 percent of cases) or in other community settings such as a church, bar, beauty salon or prison (accounting for 8 percent of cases).
"Certain networks spanned multiple homes, family generations, and community settings," the study team writes.
Complicating control is that people can be infectious before they know they have drug-resistant TB.
"We know people transmit (the disease) for weeks or months before they come for a diagnosis," said Gandhi, an associate professor of epidemiology, global health and infectious diseases at Emory.
"You have to focus on stopping the chain of transmission," he said. "You have to identify early and intervene early. When you diagnose, drug susceptibility should be part of that diagnosis. And we have to do a better job creating facilities where transmission doesn't take place, particularly in healthcare settings, hospitals, homeless shelters in the United States and in schools and workplaces."
The other researchers involved in the study were from the U.S. Centers for Disease Control and Prevention in Atlanta, the Albert Einstein College of Medicine in New York and the University of KwaZulu-Natal in South Africa, the province of 10.3 million people where the study was done.