Monday, April 2, 2018
Scientists have developed a novel technique that prevents coronary artery obstruction during transcatheter aortic valve replacement (TAVR), a rare but often fatal complication. The method, called Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction (BASILICA), will increase treatment options for high-risk patients who need heart valve procedures. The findings by researchers at the National Institutes of Health will publish in the Journal of the American College of Cardiology: Cardiovascular Interventions on April 2.
TAVR, a procedure used to treat aortic valve stenosis, involves threading a long, thin, flexible tube, called a catheter, through the femoral artery in the leg to the heart. Aortic valve stenosis is a fatal narrowing of the valve controlling blood leaving the heart to the rest of the body. This narrowing reduces blood flow to vital organs, resulting in shortness of breath, chest pain, blackouts, and heart failure.
For elderly or frail patients, TAVR offers an effective and less invasive alternative to open heart surgery. However, a small subset of these patients may develop coronary artery obstruction during the TAVR procedure. For more than half the patients who experience coronary artery obstruction during the TAVR, this complication has been fatal.
BASILICA was developed by Jaffar M. Khan, M.D., at the National, Heart, Lung, and Blood Institute (NHLBI), part of NIH, to increase the safety of TAVR for this subset of patients.
“These patients are either not eligible for conventional TAVR, or they are at high risk for it,” said Robert J. Lederman, M.D., the senior investigator in NHLBI’s Division of Intramural Research who led the study with Khan.
Illustration of the BASILICA procedure. (A) a catheter directs an electrified guidewire through the base of the left aortic cusp into a snare in the left ventricular outflow tract; (B) after snare retrieval, the mid-shaft of the guidewire is electrified to lacerate the leaflet (C); (D) the leaflet splays after TAVR permitting coronary flow.
Thursday, March 29, 2018
Researchers identify protective role of iron export protein and its mutation
Researchers at the National Institutes of Health have a possible explanation for why iron can sometimes worsen malaria infection. By studying mice and samples from malaria patients, the researchers found that extra iron interferes with ferroportin, a protein that prevents a toxic buildup of iron in red blood cells and helps protect these cells against malaria infection. They also found that a mutant form of ferroportin that occurs in African populations appears to protect against malaria. These basic findings, published in Science, may help researchers and healthcare officials develop strategies to prevent and treat malaria infections, which numbered nearly 216 million worldwide in 2016.
“Our study helps solve a long-standing mystery,” said Tracey Rouault, M.D., the study’s senior author and a senior investigator at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Iron supplements can sometimes worsen malaria infection and, conversely, iron deficiency can be protective in some cases. Our findings reveal that ferroportin — its function, as well as its regulation by iron levels — helps to explain these observations.”
Electron micrograph of red blood cells infected with Plasmodium falciparum, the parasite that causes malaria in humans. During its development, the parasite forms protrusions called 'knobs' on the surface of its host red blood cell which enable it to avoid destruction and cause inflammation.
Wednesday, March 28, 2018
NIH scientists discover macromolecular complexes that could enable medication development
Scientists at the National Institute on Drug Abuse (NIDA) Intramural Research Program (IRP) have uncovered evidence that shows a more complex and elaborate role for the body’s hard-working G protein-coupled receptors (GPCRs) than previously thought, suggesting a conceptual advance in the fields of biochemistry and pharmacology. With more than 800 members in the human genome, GPCRs are the largest family of proteins involved in decoding signals as they come into the cell and then adapt the cell’s function in response. NIDA is part of the National Institutes of Health.
Manipulating how cells respond to signals is key to developing new medications. Although pharmacologists have studied GPCRs for many years, there is still a debate on how they operate — are they isolated units that randomly collide with each other or are they deliberately coupled together to receive signals? The NIDA scientists conclude that GPCRs form part of very elaborate pre-coupled macromolecular complexes. Simply put, they act as little computing devices that optimally gather and process information coming into the cell, allowing the cells to adapt and change their function.
“These findings represent many years of complex and highly nuanced science, following the trail as chemical signals travel through the body at the cellular level,” said NIDA Director Nora D. Volkow, M.D. “This remarkable discovery will open new avenues for medication development for addiction, pain and other conditions, offering more precise targets with fewer side effects.”
“The specific macromolecular complex investigated in this study has therapeutic implications not only for addiction, but also for Parkinson’s disease and schizophrenia,” said Dr. Sergi Ferré, who led the team of scientists. “Discovering that these protein interact with other signals in preformed complexes gives us more precise targets for medication development.”
Computational model of a macromolecular complex.
Monday, March 26, 2018
Diuretic therapy — commonly given to extremely preterm infants to help them overcome respiratory problems — appears to offer no benefit for this purpose, according to an analysis by researchers at the National Institutes of Health. Surprisingly, infants in the study who received diuretic therapy were more likely to require respiratory support, compared to extremely preterm infants with similar respiratory problems who did not receive the therapy. The study is published in The Journal of Pediatrics.
Diuretic medicines prompt the kidneys to make more urine. The therapy is commonly given to preterm infants to help drain fluid from the lungs, but there is little research evidence to support the practice.
Researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Heart, Lung, and Blood Institute (NHLBI) analyzed data collected as part of the Prematurity and Respiratory Outcomes Program study, an effort to understand respiratory difficulties in extremely premature infants during the first year of life. The study included 835 infants born between 23 and 28 weeks at 13 U.S. neonatal intensive care units. An infant is considered full term at 39 weeks.
Wednesday, March 21, 2018
NIH discovery in mice could lead to therapies to reduce vision loss from diseases of the retina
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish their normal organization and function. The findings point to potential therapies for controlling inflammation and slowing progression of rare retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), the most common cause of blindness among Americans 50 and older. A report on the study was published online today in Science Advances. The NEI is part of the National Institutes of Health.
“Neuroinflammation is an important driver of the death of neurons in retinal diseases,” said Wai T. Wong, M.D., Ph.D., chief of the NEI Section on Neuron-Glia Interactions in Retinal Disease, and the study’s lead investigator. “Our study is foundational for understanding ways to control the immune system in the retina.” Control of the immune system is important for developing new treatments for a variety of eye conditions, including AMD, RP, or for certain types of retinal injury.
Microglia in a healthy adult mouse retina.
Wednesday, March 21, 2018
Kinesin family member 5A (KIF5A), a gene previously linked to two rare neurodegenerative disorders, has been definitively connected to amyotrophic lateral sclerosis (ALS) by an international team from several of the world’s top ALS research labs. The findings identify how mutations in KIF5A disrupt transport of key proteins up and down long, threadlike axons that connect nerve cells between the brain and the spine, eventually leading to the neuromuscular symptoms of ALS.
The discovery, published in the March 21, 2018, issue of Neuron, was led by Bryan Traynor, M.D., Ph.D., of the Intramural Research Program of the National Institute on Aging (NIA) at the National Institutes of Health and John Landers, Ph.D., of the University of Massachusetts Medical School, Worcester, with key funding support from the NIA, the National Institute of Neurological Disorders and Stroke (NINDS) at NIH, and several public and private sector organizations. Genetic data collected by teams of scientists worldwide contributed to the project.
It took a comprehensive, collaborative effort to analyze a massive amount of genetic data to pin down KIF5A as a suspect for ALS, also known as Lou Gehrig’s disease. To zero in on KIF5A, the NIH team performed a large-scale genome-wide association study, while the University of Massachusetts team concentrated on analyzing rare variants in next generation sequence data. Over 125,000 samples were used in this study, making it by far the largest such study of ALS performed to date.
An international team of ALS researchers has proven that mutations in the neuronal transport gene KIF5A are associated with ALS.
Monday, March 19, 2018
Marijuana impairment cited most in study of recent high school graduates
Roughly a third of recent high school graduates have ridden in a motor vehicle with a substance-impaired driver, according to a study by researchers at the National Institutes of Health and other institutions. The study found that during the first two years after high school graduation, 23 percent of young adults had ridden with a marijuana-impaired driver at least once, while 20 percent had ridden with an alcohol-impaired driver, and 6 percent had ridden with a driver impaired by glue or solvents or harder, illicit drugs, such as amphetamines, opioids, cocaine.
The analysis was conducted by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Colorado State University, Fort Collins; the Colorado School of Public Health, Denver; and Yale University, New Haven, Connecticut. Their results appear in the Journal of Studies on Alcohol and Drugs.
The authors analyzed data from NICHD’s NEXT Generation Health Study, a seven-year study of more than 2,700 U.S. adolescents starting at grade 10. Its goal is to identify the social, behavioral and genetic factors linked to health and healthy behaviors. Along with NICHD, funding for the NEXT Generation Health Study was provided by NIH’s National Heart, Lung, and Blood Institute and the Maternal and Child Health Bureau of the Health Resources and Services Administration.
Monday, March 19, 2018
Scientists have discovered a human antibody that protected mice from infection with the deadliest malaria parasite, Plasmodium falciparum. The research findings provide the basis for future testing in humans to determine if the antibody can provide short-term protection against malaria, and also may aid in vaccine design. Investigators at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, led the research with colleagues at the Fred Hutchinson Cancer Research Center in Seattle. Currently, there is no highly effective, long-lasting vaccine to prevent malaria, a mosquito-spread disease that causes some 430,000 deaths each year, primarily among young children in sub-Saharan Africa.
The research team isolated the antibody, called CIS43, from the blood of a volunteer who had received an experimental vaccine made from whole, weakened malaria parasites (PfSPZ Vaccine-Sanaria). The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected. In two different models of malaria infection in mice, CIS43 was highly effective at preventing malaria infection. If confirmed through additional studies in people, CIS43 could be developed as a prophylactic measure to prevent infection for several months after administration, the researchers say. Such a prophylactic antibody could be useful for tourists, health care workers, military personnel or others who travel to areas where malaria is common. Moreover, if the antibody prevented malaria infection for up to six months, it might be combined with antimalarial drugs and be deployed as part of mass drug administration efforts that potentially could eliminate the disease in malaria-endemic regions.
Tuesday, March 13, 2018
Promising concept may lead to an alternative to antibiotics
Researchers are developing a promising alternative to antibiotic treatment for infections caused by Klebsiella pneumoniae bacteria resistant to carbapenem antibiotics. The approach uses antibodies to target the K. pneumoniae protective capsule polysaccharide, allowing immune system cells called neutrophils to attack and kill the bacteria. The early stage, in vitro research was conducted by scientists at the National Institute of Allergy and Infectious Diseases’ (NIAID) Rocky Mountain Laboratories and the New Jersey Medical School-Rutgers University.
Klebsiella bacteria cause about 10 percent of all hospital-acquired infections in the United States. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is one of the antibiotic-resistant organisms labeled an urgent threat by the Centers for Disease Control and Prevention. ST258 is particularly concerning because it is resistant to most antibiotics. It is a significant cause of mortality among people with bloodstream infections.
Tuesday, March 13, 2018
Study of flies suggests neurodegenerative disorders may speed up aging process
To understand the link between aging and neurodegenerative disorders such as Alzheimer’s disease, scientists from the National Institutes of Health compared the genetic clocks that tick during the lives of normal and mutant flies. They found that altering the activity of a gene called Cdk5 appeared to make the clocks run faster than normal, and the flies older than their chronological age. This caused the flies to have problems walking or flying later in life, to show signs of neurodegeneration, and to die earlier.
“We tried to untangle the large role aging appears to play in some of the most devastating neurological disorders,” said Edward Giniger, Ph.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke and the senior author of the study published in Disease Models & Mechanisms. “Our results suggest that neurodegenerative disorders may accelerate the aging process.”
On average, the normal flies in this study lived for 47 days. To create a genetic clock, Dr. Giniger’s team measured the levels of every gene encoded in messenger RNA molecules from cells from the heads and bodies of flies at 3, 10, 30, and 45 days after birth. This allowed the researchers to use advanced analysis techniques to search for the genes that seemed to be sensitive to aging, and create a standard curve, or timeline, that described the way they changed.