Category: Injury and Illness

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Dormant Viruses Reactivate, Signaling Effect of Lingering Sepsis

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Doctors with a patient
A new study finds that people with lingering sepsis may have suppressed immune systems. Credit: Stock image.

Each year, more than 200,000 people in the United States die from sepsis, a condition caused by an overwhelming immune response that can quickly lead to organ failure. While many people with sepsis survive this immediate threat, they may die days or even months later from secondary infections.

A research team that included Richard Hotchkiss, Jonathan Green and Gregory Storch of Washington University School of Medicine in St. Louis suspected that when sepsis lasts for more than a few days, it compromises the immune system. To test this hypothesis, the scientists compared viral activity in sepsis patients, other critically ill patients and healthy individuals. They looked for viruses like Epstein-Barr and herpes-simplex that are often dormant and innocuous in healthy people but can reactivate and cause problems in those with suppressed immune systems.

Of the three study groups, sepsis patients had much higher levels of these viruses, suggesting that their immune responses may be hindered. Immune suppression could make it difficult to defend against the reactivated viruses as well as new infections like pneumonia. The team now plans to test whether immune-boosting drugs can prevent deaths in people with lingering sepsis.

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NIGMS Sepsis Fact Sheet

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Good Vibrations

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A knot-like structure in a section of RNA from a flavivirus
Findings in mice may lead to a drug-free, noninvasive way to treat chronic wounds in people with type 2 diabetes. Credit: Stock image.

For people living with type 2 diabetes, wounds often heal slowly, sometimes even becoming chronic. Now, scientists have shown that low-intensity vibrations can speed up the healing process in a strain of diabetic mice commonly used to study delayed wound healing. The research team, led by Timothy Kohof the University of Illinois at Chicago, found that exposing the mice to barely perceptible vibrations five times a week for just 30 minutes promoted wound healing by increasing the formation of new blood vessels and of granulation tissue, a type of tissue critical in the early stages of healing. If researchers can show that the vibration technique also works in humans, this approach could one day offer a drug-free, non-invasive therapy for chronic wounds in people with diabetes.

This work also was funded by NIH’s National Institute of Dental and Craniofacial Research.

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Multitarget Drugs to Challenge Microbial Resistance

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A group of purple, rod-shaped bacterial cells rendered by computer at Centers for Disease Control and Prevention by Melissa Brower.
Computer-generated image of drug-resistant Mycobacterium tuberculosis bacteria. Credit: Melissa Brower, Centers for Disease Control and Prevention.

Drugs that target a single essential protein in a microbial invader can be effective treatments. But the genomes of pathogens—including bacteria, fungi and parasites—mutate rapidly, and resistance can develop if a mutation changes a target protein’s structure. Molecules that interfere with multiple microbial proteins at once have the potential to overcome the growing problem of antimicrobial drug resistance.

Researchers led by Eric Oldfield of the University of Illinois recently explored whether an experimental drug called SQ109, developed to treat tuberculosis (TB), could be tweaked to attack multiple enzymes, as well as to kill different types of microbes. The scientists succeeded in creating several multitarget analogs of SQ109 that were more effective than the original drug at killing their target pathogens in laboratory experiments. These analogs included one compound that was five times more potent against the bacterium that causes TB while also being less toxic to a human cell line tested.

This work was also funded by the National Cancer Institute; the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases and the NIH Office of the Director.

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Study Comparing Sepsis Treatment Methods Shows Equivalent Survival Rates

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Doctors and a patient in a hospital
A 5-year, randomized clinical trial helped resolve a long-standing debate about how best to manage sepsis patients.

For years, doctors have debated the best ways to identify, predict and treat sepsis. The condition, which is usually triggered by infection, is marked by body-wide inflammation and can lead to a dangerous drop in blood pressure known as septic shock. Sepsis affects more than 800,000 people each year and kills about 20 to 30 percent of them. It’s the most expensive condition treated in U.S. hospitals, costing more than $20 billion a year.

Now, a nationwide, 5-year clinical trial that set out to compare three different treatment approaches has shown that survival of patients with septic shock was the same regardless of whether they received treatment based on structured, standardized medical plans (protocols) or the usual high-level standard of care. If patients were diagnosed shortly after the onset of sepsis and treated promptly with fluids and antibiotics, they did equally well whether they received treatment based on either of two specific protocols—one less invasive than the other—or got the usual, high-level care provided by the academic hospitals where the study was conducted.

According to the study’s leaders, the trial “helps resolve a long-standing clinical debate about how best to manage sepsis patients, particularly during the critical first few hours of treatment,” and shows that “there is not a mandated need for more invasive care in all patients.”

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NIGMS News Release
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New England Journal of Medicine Article
Sepsis Fact Sheet

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Nanoparticles Developed to Stick to Damaged Blood Vessels, Deliver Drugs

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Artery with fat deposits and a formed clot. Credit: Stock image.
Artery with fat deposits and a formed clot. Credit: Stock image. View larger image

Heart disease is the leading cause of death for both men and women in the United States, according to the Centers for Disease Control and Prevention. One treatment challenge is developing non-invasive ways to direct medication to damaged or clogged arteries, which can block blood flow and increase the risk for heart attack and stroke. A team led by Naren Vyavahare at Clemson University has engineered extremely tiny particles—nanoparticles—that offer a promising step forward.

Healthy arteries have elastic fibers that make the arteries flexible. But, in most cardiovascular diseases, the fibers get damaged. The new nanoparticles, which can deliver drugs, attach only to damaged fibers and could enable site-specific drug delivery to minimize off-target side effects. The nanoparticles also allow drugs to be released over longer periods of time, potentially increasing the drugs’ effectiveness. The new biomaterial was tested in rodent models for studying vascular disease, so it is still in the early stages of development.

This work also was funded by NIH’s National Heart, Lung, and Blood Institute.

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Epilepsy Drug Improves Health in Animal Model of Obesity

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Liver cells of obese mice treated with valproic acid (right) and untreated obese mice (left).
Liver cells (magenta) of obese mice treated with valproic acid (right) had much less fat accumulation (white) than those of untreated obese mice (left). Credit: Lindsay B. Avery and Namandjé N. Bumpus, Johns Hopkins University. View larger image

With more than 90 million Americans affected by obesity, developing medications to help combat weight gain and its associated diseases has become a priority. In a study using obese mice, a team led by Namandjé Bumpus of Johns Hopkins University recently showed that a commonly prescribed epilepsy drug, valproic acid, reduced fat accumulation in the liver and lowered elevated blood sugar levels like those associated with type 2 diabetes. Body weight also stabilized in mice given the drug, whereas untreated mice continued to gain weight. Additional experiments in mouse and human liver cells suggested that the byproducts of valproic acid produced as the body breaks down the drug, rather than valproic acid itself, were responsible for the observed effects. These byproducts achieved the same effects in cells at one-fortieth the concentration of valproic acid, making them promising candidates for further drug development.

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Bumpus Laboratory

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Protein Triggers Inflammatory Responses in Hemorrhage and Sepsis

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Doctors helping a patient. Credit: U.S. Navy.
Inflammation is part of the body’s natural response to trauma, but when it becomes widespread, it can lead to sepsis. Credit: U.S. Navy.

Inflammation is part of the body’s natural response to trauma, playing a vital role in wound healing and prevention of infection. However, when inflammation becomes widespread, or systemic, it can lead to sepsis, a condition that can damage organs and cause death. Scientists led by Ping Wang of the Feinstein Institute for Medical Research have found a way to potentially target harmful systemic inflammation. They identified a protein–cold-inducible RNA-binding protein (CIRP)–that triggers inflammatory responses during hemorrhagic shock and sepsis. Wang then hypothesized that blocking CIRP activity might mitigate the body’s overall inflammatory response and improve patient survival. In a preclinical study using mice, an antibody against CIRP decreased mortality after hemorrhage and sepsis. The molecule could lead to the development of an anti-CIRP drug.

This work also was funded by the NIH Office of the Director and NIH’s National Heart, Lung, and Blood Institute.

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Fact Sheets on Physical Trauma and Sepsis
The Body’s Response to Traumatic Injury Video

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Meet Brad Duerstock

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Brad Duerstock
Brad Duerstock
Fields: Neuroscience, assistive technology design
Works at: Purdue University, West Lafayette, IN
Hobbies: Gadgetry, architectural design
Bizarre collectible: Ecuadorian shrunken head (not a real one—it’s a replica made from goatskin)
Credit: Andrew Hancock, Purdue University

At the age of 18, Brad Duerstock had a devastating accident. A star member of his high school swim team, Duerstock hit his head during practice in a way that broke his neck and paralyzed all of his limbs. Today, he studies spinal cord injuries much like his own, investigating how the damage occurs and how it could possibly be repaired.

Duerstock has worked to make science accessible to people with disabilities, whether they use wheelchairs, as he does, or have visual or other impairments. For example, he has redesigned laboratory space to make it easier for people with disabilities to navigate and perform tasks.

“I like knowing that what I do can ultimately impact others,” Duerstock says.

Duerstock’s Findings

Much of Duerstock’s research deals with what occurs immediately following a nerve injury. In a spinal cord injury, nerve tissue becomes severed or dies. The immune response and bleeding in the injured area can cause extra damage to nerves in the spinal cord. Duerstock and his team have found that a molecule called acrolein is produced in spinal cord injuries and that it kills the nerves it encounters as it spreads around the injury site. They have been investigating a compound called polyethylene glycol (PEG), a polymer that could seal ruptured nerve cell membranes, possibly protecting nerve tissue from further damage immediately following a spinal cord injury.

Duerstock also founded and leads the Institute for Accessible Science (IAS), a community of scientists, students, parents and teachers whose goal is to promote better accommodations for people with disabilities who are studying or working in the sciences. The IAS looks into how to redesign lab spaces and equipment to increase accessibility for people with disabilities, particularly those with limited mobility or vision.

Although Duerstock originally wanted to be a doctor, he believes his true calling is in research. “The sense of discovery and the impact on others are big motivations for me,” says Duerstock. “Being a researcher, you might have a broader impact on society than you would as a practicing physician.”

Content adapted from the NIGMS Findings magazine article Opening Up the Lab.

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Protein May Help Reduce Intestinal Injury

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HB-EGF protein. Credit: National Center for Microscopy and Imaging Research.
HB-EGF has the potential to protect the intestines (magnified here) from different types of injury. Credit: National Center for Microscopy and Imaging Research.

Gail Besner of Nationwide Children’s Hospital and her research team recently found out how the HB-EGF growth factor protein could potentially aid the development of treatments for a number of conditions. Using model systems in two separate studies, the scientists discovered that HB-EGF could protect the intestines from injury by stimulating cell growth and movement and by decreasing substances formed upon intestinal injury that worsen the damage. They also showed that administration of mesenchymal stem cells could further shield the intestines from injury. Future treatments involving a combination of HB-EGF and stem cells could, for example, help cancer patients sustain fewer intestinal injuries resulting from radiation therapy.

This work also was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases.

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Meet David Patterson

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David Patterson
David Patterson
Field: Psychology
Works at: University of Washington, Seattle
Alternative career: Full-time rock ‘n’ roll drummer
Hobbies: Part-time rock ‘n’ roll drummer (with his band, the Shrinking Heads)
Credit: Clare McLean, UW Medicine Strategic Marketing & Communications

The pain stemming from second- and third-degree burns is among the worst known. Throughout recovery, the intense, disabling pain patients feel can lead to sleeplessness, anxiety and depression.

David Patterson first entered a burn ward as a psychologist hoping to help patients cope with these issues. He saw patients refuse wound cleaning because of how painful it could be.

“I’ve learned how horribly difficult it is to control burn and trauma pain with medications alone,” he says. “The amount of pain people feel affects how well they adjust in the long term.” Pain and the mental, social and emotional problems it causes also hinder the body’s ability to heal physically.

Today, Patterson is committed to helping burn patients overcome pain, allowing their bodies—as well as their minds—to heal more efficiently. Using virtual reality (VR) technology, Patterson has found an effective complement to pain-relieving drugs such as morphine and other opioid analgesics.

Patterson’s Findings

“To be honest, for acute pain, you give someone a shot or a pill and it’s instant relief,” Patterson says. But opioid analgesics carry problems.  Sometimes patients don’t respond well to morphine or require high dosages that carry strong side effects.

When burn patients undergo routine wound care, the pain can be excruciating—as bad as or worse than the original burn incident. Realizing the brain can take only so many stimuli, Patterson collaborated with fellow UW psychologist Hunter Hoffman to experiment with VR in pain relief. When combined with minimal pain medications, VR is a powerful solution to acute pain. By providing a computer-generated reality—for example, an icy canyon filled with snowmen and Paul Simon’s music, as in the case of their creation SnowWorld—the patient’s eyes, ears and mind are so occupied that he or she can effectively ignore the pain.

Patterson and his team found that VR pain reduction strategies are as powerful as opioid analgesics, without the negative side effects. The technology doesn’t require specialized expertise and is getting progressively less expensive, making it economically attractive.  At least eight hospitals have adopted the methods as part of their clinical program, allowing Patterson an opportunity to conduct further studies on the long-term effects of using these complementary methods and the efficacy of the techniques on other kinds of pain.

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