Syndicate content

Archive - Aug 1, 2013

Date

Scientists Identify Staph-Killing Compound That May Be Effective in Osteomyelitis

Osteomyelitis, a debilitating bone infection most frequently caused by Staphylococcus aureus ("staph") bacteria, is particularly challenging to treat. Now, Vanderbilt microbiologist Eric Skaar, Ph.D., M.P.H., and colleagues have identified a staph-killing compound that may be an effective treatment for osteomyelitis, and they have developed a new mouse model that will be useful for testing this compound and for generating additional therapeutic strategies. James Cassat, M.D., Ph.D., a fellow in Pediatric Infectious Diseases who is interested in improving treatments for children with bone infections, led the mouse model studies. Working with colleagues in the Vanderbilt Center for Bone Biology and the Vanderbilt University Institute of Imaging Science, Dr. Cassat developed micro-computed tomography (micro-CT) imaging technologies to visualize a surgically introduced bone infection in progress. "The micro-CT gives excellent-resolution images of the damage that's being done to the bone," said Dr. Skaar, the Ernest W. Goodpasture Professor of Pathology. "We found that staph is not only destroying bone, but it's also promoting new bone growth. Staph is causing profound changes in bone remodeling." Dr. Cassat also established methods for recovering -- and counting -- bacteria from the infected bone. "We're not aware of any other bone infection models where you can pull the bacteria out of a bone and count them in a highly reproducible manner," Dr. Skaar said. "From a therapeutic development standpoint, we think this model is going to allow investigators to test new compounds for efficacy against bone infections caused by staph or any other bacteria that cause osteomyelitis." Several pharmaceutical companies have already approached Dr.

Japanese Scientists ID Inflammatory On/Off Switch for Allergic Asthma and COPD

Japanese researchers have made a new step toward understanding—and learning how to stop—runaway inflammation for both chronic obstructive pulmonary disorder (COPD) and allergic asthma. In a new report appearing in the August 2013 issue of The FASEB Journal the scientists show that two receptors of an inflammatory molecule, called "leukotriene B4," play opposing roles in turning inflammation on and off for allergic asthma and COPD. The first receptor, called "BLT1," promotes inflammation, while the second receptor, called "BLT2," has a potential to weaken inflammation during an allergic reaction. This discovery also is important because until now, BLT2 was believed to increase inflammatory reaction. "Leukotriene B4 levels are elevated in the airways of the patients with asthma and COPD, and the opposite role of BLT1 and BLT2 in allergic inflammation implies that drug development should target BLT1 and BLT2 differently," said Hiromasa Inoue, M.D., study author from the Department of Pulmonary Medicine at the Graduate School of Medical and Dental Sciences at Kagoshima University in Kagoshima, Japan. "We hope that better anti-asthma drugs or anti-COPD drugs will be produced in the future to treat millions of patients who suffer from severe asthma and COPD." To make this discovery, scientists compared the allergic reactions in BLT2-gene deleted mice to those in normal mice. Then an allergic asthma reaction was provoked by inhalation of allergens. BLT2-gene deleted mice showed more inflammatory cells in the lung compared to normal mice. Without the BLT2 gene, lung allergic inflammation was stronger than that of normal mice. The production of interleukin-13, an important mediator of allergic inflammation from T lymphocytes, was increased in the group without the BLT2 gene.

Fetal Stress May Cause Epigenetic Changes That Pose Long-Term Risk Factors for Chronic Disease

If you think stress is killing you, you may be right, but what you don't know is that stress might have harmed your health even before you were born. In a new report appearing in the August 2013 issue of The FASEB Journal, Harvard researchers find that epigenetic disruptions, which are associated with chronic disease later in life, are already common at birth. Possibly, these aberrations result from stressors in the intrauterine environment (e.g., maternal smoking, maternal diet, or high levels of endocrine-disrupting chemicals). This finding supports the belief that seeds of disease are sown before birth, increasing the importance of optimal prenatal care. "This study may help us understand whether epigenetic mechanisms contribute to chronic disease susceptibility already prior to birth," said Karin Michels, Sc.D., Ph.D., study author from Harvard Medical School. "We are currently exploring which stressors during prenatal life may contribute to these epigenetic disruptions." To make this discovery, Dr. Michels and colleagues examined the expression pattern of imprinted genes important for growth and development. Researchers analyzed the parental expression pattern in the cord blood and placenta of more than 100 infants and followed up this analysis with methylation and expression studies. The results lent credence to the emerging theme that susceptibility to disease may indeed originate in utero. Additionally, this research showed that a high degree of disruption occurred during the imprinting of a gene called IGF2, which was expressed from both alleles in the cord blood of 22 percent of study subjects. Loss of imprinting of IGF2 has been associated with several cancers, including Wilms tumor, colorectal and breast cancer, and childhood disorders such as Beckwith-Wiedemann syndrome.