Newly Discovered Reactions From An Old Drug May Lead To New Antibiotics

A mineral found at health food stores could be the key to developing a new line of antibiotics for bacteria that commonly cause diarrhea, tooth decay and, in some severe cases, death.The trace mineral selenium is found in a number of proteins in both bacterial cells and human cells called selenoproteins. University of Central Florida Associate Professor William Self's research shows that interrupting the way selenoproteins are made can halt the growth of the super bug Clostridium difficile and Treponema denticola, a major contributor to gum disease.

Infections of Clostridium difficile (commonly known as C-diff) lead to a spectrum of illnesses ranging from severe diarrhea to colitis, which can cause death. It's a life-threatening problem in hospitals and nursing homes worldwide, and the number of cases is on the rise. There are an estimated 500,000 cases per year in the United States alone. Between 15,000 to 20,000 people die each year while infected with this superbug. Treponema denticola is one of leading causes of gum disease and costs individuals thousands of dollars in dental care each year.

Self's findings are published in the May and June editions of the Journal of Biological Inorganic Chemistry and the Journal of Bacteriology. The National Institutes of Health and the Florida Department of Health funded the research, which was conducted at UCF during the past three years.

"It's the proof of principle that we are excited about," Self said from his research lab at UCF. "No one has ever tried this approach, and it could potentially be a source for new narrow spectrum antibiotics that block bacteria that require selenium to grow."

The key discovery occurred when the team found that the gold drug Auranofin, used to treat arthritis, impacted selenium's metabolism process. The chemical reaction changes the selenium, which prevents bacteria from using it to grow. Auranofin is an FDA-approved gold salt compound that is used to control inflammation and is already known to inhibit the activity of certain selenoproteins. Since certain bacteria, such as C. difficile, require selenoproteins for energy metabolism, the drug acts as a potent antimicrobial halting the growth of the bacteria.

The initial studies with C. difficile led to studies with T. denticola, known for several years to require selenium for growth. While testing the gold salt, Self's group also uncovered another surprise; the stannous salts found in many antimicrobial toothpastes in the form of stannous fluoride also inhibited the synthesis of selenoproteins. Previous independent research had already established that stannous salts are more effective at preventing tooth decay and inhibiting growth of T. denticola, but the mechanism of this inhibition of growth was not yet known. These findings could lead to new approaches to preventing gum disease.

"No one has tried to block the metabolism of selenium before as a therapeutic approach," Self said. "That's what's new and exciting and could lead to a whole host of other possibilities, including a better understanding of how the gold salt works for arthritis."

Self said more research is needed, and he already has another grant proposal before the NIH that would move his research forward.

Feeling Close To A Friend Increases Progesterone, Boosts Well-being And Reduces Anxiety And Stress

Why does dishing with a girlfriend do wonders for a woman's mood?

A University of Michigan study has identified a likely reason: feeling emotionally close to a friend increases levels of the hormone progesterone, helping to boost well-being and reduce anxiety and stress.

"This study establishes progesterone as a likely part of the neuroendocrine basis of social bonding in humans," said U-M researcher Stephanie Brown, lead author of an article reporting the study findings, published in the current (June 2009) issue of the peer-reviewed journal Hormones and Behavior.

A sex hormone that fluctuates with the menstrual cycle, progesterone is also present in low levels in post-menopausal women and in men. Earlier research has shown that higher levels of progesterone increase the desire to bond with others, but the current study is the first to show that bonding with others increases levels of progesterone. The study also links these increases to a greater willingness to help other people, even at our own expense.

"It's important to find the links between biological mechanisms and human social behavior," said Brown, is a faculty associate at the U-M Institute for Social Research (ISR) and an assistant professor of internal medicine at the U-M Medical School. She is also affiliated with the Ann Arbor Veterans Affairs Hospital. "These links may help us understand why people in close relationships are happier, healthier, and live longer than those who are socially isolated."

Progesterone is much easier to measure than oxytocin, a hormone linked to trust, pair-bonding and maternal responsiveness in humans and other mammals. Oxytocin can only be measured through an invasive spinal tap or through expensive and complex brain imaging methods, such as positron emission tomography scans. Progesterone can be measured through simple saliva samples and may be related to oxytocin.

In the current study, Brown and colleagues examined the link between interpersonal closeness and salivary progesterone in 160 female college students.

At the start of the study, the researchers measured the levels of progesterone and of the stress hormone cortisol in the women's saliva, and obtained information about their menstrual cycles and whether they were using hormonal contraceptives or other hormonally active medications.

To control for daily variations in hormone levels, all the sessions were held between noon and 7 p.m.

The women were randomly assigned to partners and asked to perform either a task designed to elicit feelings of emotional closeness or a task that was emotionally neutral.

In the emotionally neutral task, the women proofread a botany manuscript together.

After completing the 20-minute tasks, the women played a computerized cooperative card game with their partners, and then had their progesterone and cortisol sampled again.

The progesterone levels of women who had engaged in the emotionally neutral tasks tended to decline, while the progesterone levels of women who engaged in the task designed to elicit closeness either remained the same or increased. The participants' cortisol levels did not change in a similar way.

Participants returned a week later, and played the computerized card game with their original partners again. Then researchers measured their progesterone and cortisol. Researchers also examined links between progesterone levels and how likely participants said they would be to risk their life for their partner.

"During the first phase of the study, we found no evidence of a relationship between progesterone and willingness to sacrifice," Brown said. "But a week later, increased progesterone predicted an increased willingness to say you would risk your life to help your partner."

According to Brown, the findings are consistent with a new evolutionary theory of altruism which argues that the hormonal basis of social bonds enables people to suppress self-interest when necessary in order to promote the well-being of another person, as when taking care of children or helping ailing family members or friends.

The results also help explain why social contact has well-documented health benefits---a relationship first identified nearly 20 years ago by U-M sociologist James House.

"Many of the hormones involved in bonding and helping behavior lead to reductions in stress and anxiety in both humans and other animals. Now we see that higher levels of progesterone may be part of the underlying physiological basis for these effects," Brown said.

Chicken Meat: Organic Acids, Plant Extracts And Irradiation Combine To Beat The Bacteria

A mixture of some organic acids and some extracts from plants turns out to be enough to greatly reduce pathogenic bacteria on chicken breast meat. Add some irradiation to the mix and it makes a lethal combination against the bacteria.Food Safety Consortium researchers at the University of Arkansas System’s Division of Agriculture found that they could greatly reduce E. coli O157:H7, Listeria monocytogenes and Salmonella Typhimurium in the chicken breast meat by infusing combinations of organic acids – acetic, citric, lactic, malic and tartaric – into the meat. The experiments were also performed with extracts from green tea and grape seeds in combination with the acids.

Three of the organic acids – malic, citric and tartaric – were most effective against S. Typhimurium and E. coli O157:H7, more than against L. monocytogenes. With irradiation factored in, the results were significant against all the pathogens.

“We want to determine the least amount of plant extracts that we can use and the least amount of irradiation dosage to get the best inhibitory effect,” said Navam Hettiarachchy, a UA food science professor who supervised the project.

Previous research by Hettiarachchy’s research team showed that extracts from grape seed and green tea reduced L. monocytogenes to undetectable levels when applied in combination with nisin, a bacteriocin recognized as a safe food preservative.

The researchers are also using the plant extracts to serve as antioxidants, which minimizes lipid oxidation. Lipid oxidation is a process that causes meat quality to deteriorate by adversely affecting characteristics such as flavor, color and texture.

Hettiarachchy said the research team has examined the effects of irradiation on the chicken’s color and texture and found no significant change.

The research is continuing, but Hettiarachchy said a poultry company has already expressed interest in the project’s findings. Irradiation, however, has not yet been applied widely in the United States as many companies have worried about potential resistance among consumers.

Hettiarachcy suggested that labels on irradiated products could have a brief explanation of irradiation to educate consumers.

“I am hopeful that with time the public will become aware of irradiation processing so that they accept irradiation in processing poultry and meat products for safety against pathogens,” Hettiarachchy said. “A new education component is very important and may be the key for acceptance for irradiated food products by the consumer.”