Bling Beats Bad Bugs
A bit of silver could be good for what ails you. In a series of experiments, researchers have found that ionic silver boosts the efficacy of common antibiotics, helps overcome antibiotic resistance, and can even extend the range of some widely used drugs.
Investigators led by James Collins, PhD, of Boston University studied the ways that silver -- long touted as an anti-microbial -- interacts with bacterial cells. It turned out that the metal disrupts several bacterial cellular processes, leading to increases in reactive oxygen species and membrane permeability.
In vitro, adding silver to antibiotics restored susceptibility to tetracycline in a drug-resistant strain of Escherichia coli. In mice with urinary tract infections, silver alone or gentamicin alone had no effect, but the combination significantly reduced bacterial loads. As well, the investigators reported in Science Translational Medicine, adding silver to the Gram-positive-specific antibiotic vancomycin allowed the drug to penetrate and kill Gram-negative bacteria.
"Silver could be incredibly valuable as an adjunct to existing antibiotic treatments," Collins said in a statement, especially since toxicity studies showed no harm to the mice at the levels needed to boost antibiotics.
-- Michael Smith
Platelets and the Life-or-Death Response
Circulating platelets play a crucial role in the rapid immune response to bacterial pathogens, actively "touching" specialized cells in the liver to detect trapped bacteria before the larger immune system can mobilize and neutralize the invaders.
If bacteria are present on Kupffer cells, which reside in liver sinusoids and are responsible for the ultimate removal of pathogens, platelets can bind to them and seal them off from the host immediately while awaiting the arrival of neutrophils and other activated immune cells, which can take several hours.
This previously unrecognized patrolling mechanism for platelets was demonstrated using high-power imaging of the liver in animal models, Connie H.Y. Wong, of the University of Calgary in Alberta, reported in Nature Immunology.
The researchers found that mice lacking adhesion receptors on the surface of Kupffer cells succumbed rapidly when infected with Staphylococcus aureus or Bacillus cereus, whereas animals with intact Kupffer cell adhesion had much less polycythemia and fluid loss -- and were more likely to survive -- because of their almost instantaneous life-or-death platelet response.
-- Nancy Walsh
Dad's Poor Eating Habits May Affect Junior
A father's diet may influence body weight in his offspring, a mouse study suggested.
Felicia Nowak, MD, PhD, of Ohio University, and colleagues explored whether epigenetic modification of gene expression in male mice made obese from eating a high-fat diet could be transmitted to their offspring. Two groups of male mice -- one eating a high-fat diet and one eating a low-fat diet -- were mated to female mice eating a low-fat diet. The resulting offspring were fed normal mouse chow.
As Nowak reported at the Endocrine Society meeting in San Francisco, male offspring born to obese fathers had a higher body fat percentage at age 6 months and greater body weight at 6 weeks, 6 months, and 1 year (roughly equal to a span from adolescence to older adulthood in humans) compared with male offspring born to control fathers.
There were also some differences in where the body fat was deposited and in physical activity levels. Surprisingly, the male offspring of obese fathers actually showed increases in voluntary running at 6 weeks compared with the controls.
Nowak said that she thinks the findings can be explained by "epigenetic mechanisms because of the rapid induction of these inherited differences over just one generation."
-- Todd Neale
Mice Mellow Out on 'Happy Chemical'
Secondary inhibition of serotonin reuptake in mice enhanced the therapeutic effects of a commonly used antidepressant.
Co-administration of decynium-22 (D-22) and fluvoxamine more effectively blocked serotonin clearance to increase levels of the "happy chemical," enhancing antidepressant activity, as reported June 18 in the Journal of Neuroscience.
A member of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, fluvoxamine works by blocking the serotonin transporter (SERT) to increase circulating levels of serotonin in the brain. However, secondary transporters, known as organic cation transporters (OCT), are unaffected by SSRIs and continue to act like serotonin "vacuum cleaners." The OCT effect might explain the usually slow onset and limited efficacy of SSRIs, according to Lyn Daws, PhD, of the University of Texas Health Science Center at San Antonio.
By blocking OCT, D-22 helped create a larger pool of serotonin.
Though unsuitable for use in humans, D-22 may help scientists identify new therapeutic targets in the brain, such as OCT, for which new classes of antidepressants can be developed, said Daws.
-- Charles Bankhead
Dementia Target Makes for Faster, Dumber Mice
Elevated levels of acetylcholine -- a nervous system neuromodulator -- may disrupt attention and working and spatial memory but improve motor endurance, researchers wrote in the Journal of Neuroscience.
Acetylcholine is reduced in patients with cognitive failure, and increasing amounts of the neurotransmitter may be a therapeutic target for Alzheimer's disease, according to Marco Prado, PhD, of the University of Western Ontario in Canada, and colleagues.
Prado and co-authors bred mice to produce three times the normal amount of acetylcholine before subjecting them to a touch screen test that involved pressing lit-up areas of a touch screen to receive a reward. The modified mice failed the task versus control mice.
The researchers nicknamed the modified rodents "Forrest Gump mice" due to their ability to run twice as far as control mice before tiring -- an effect of the neurotransmitter's drive of muscle contractions.
The authors noted the modified mice had short attention spans and dysfunctional working and spatial memory, implying that the boost of acetylcholine causes the brain to lose the ability to determine what is relevant.
-- Cole Petrochko
By Chris Kaiser, Cardiology Editor, MedPage Today 