Tuesday, January 21, 2020
A National Institutes of Health study found that chronic treatment with mirabegron, a drug approved to treat overactive bladder, activated brown fat in a small group of healthy women and had several other beneficial metabolic effects. Brown fat, or brown adipose tissue, is a form of fat that burns calories to generate heat. The research, led by Aaron Cypess, M.D., Ph.D., at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published on Jan. 21 in the Journal of Clinical Investigation.
Fourteen women aged 18-40 of diverse ethnicities participated in the study at the NIH Clinical Center’s Metabolic Clinical Research Unit. For four weeks, each participant received daily doses of 100 mg of mirabegron, an amount exceeding the 50 mg maximum dosage approved by the U.S. Food and Drug Administration.
At four weeks, the participants’ brown fat activity had more than doubled since the first day, though their body weight and body mass stayed the same. Other changes included:
- Increased resting energy expenditure
- Higher levels of HDL (high-density lipoprotein) cholesterol — often referred to as “good” cholesterol — and bile acids, which help digest fats and regulate cholesterol
- Improved processing and regulation of blood glucose (blood sugar)
Human brown adipose tissue, or brown fat.
Photo courtesy of the Journal of Clinical Investigation
Thursday, January 16, 2020
NIH study shows treatment recommendations impacted by patient and physician factors
During their first physician visit, patients experiencing newly diagnosed chronic musculoskeletal pain are prescribed opioids more often than physical therapy, counseling, and other nonpharmacologic approaches, according to a new study published in the Journal of Pain. The use of opioids over other approaches stands in contrast with clinical recommendations for the use of nonopioid pain approaches and nonpharmacologic approaches. The study included authors from the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health; the University of Montreal; and McMaster University in Hamilton, Ontario, Canada.
“Particularly when the patient is experiencing pain that may become chronic, that first clinical encounter can set the course for patient care moving forward,” said Helene Langevin, M.D., director of NCCIH. “This study was designed to assess the ways in which real-world practice compares and contrasts with practice guidelines for these initial patient encounters.”
Study authors analyzed data from the National Ambulatory Medical Care Survey (NAMCS), conducted between 2007 and 2015. The survey data are collected by the Centers for Disease Control and Prevention’s National Center for Health Statistics and represent how medical care services are used in the United States. The results concur with the high prevalence of chronic musculoskeletal pain in the United States, with an average of 36.8 million initial visits (for a new chronic pain problem) per year or approximately 11.8% of the population.
Tuesday, January 7, 2020
Dietary supplements containing zinc and folic acid — marketed as a treatment for male infertility — do not appear to improve pregnancy rates, sperm counts or sperm function, according to a study conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health. The study appears in the Journal of the American Medical Association.
The authors note that most so-called fertility supplements contain zinc and folic acid. Zinc is an essential mineral for sperm formation, and folate, the natural form of folic acid, depends on zinc to help form DNA in the sperm. Previous studies of these nutrients as a treatment for male infertility have produced conflicting results.
“Our study is one of the first randomized, placebo-controlled trials to assess whether folic acid and zinc supplements help to improve male fertility,” said Enrique Schisterman, Ph.D., of the NICHD Division of Intramural Population Health Research, who conducted the trial, along with colleagues. “Our results suggest that these dietary supplements have little to no effect on fertility and may even cause mild gastrointestinal symptoms.”
Thursday, January 2, 2020
Tuberculosis (TB), an ancient disease, is the leading infectious cause of death globally, yet the world’s only licensed TB vaccine, Bacille Calmette-Guerin (BCG), was developed a century ago. Given to infants via a needle placed just under the skin, BCG protects babies from a form of the disease called disseminated TB but is far less effective at preventing pulmonary TB, the major cause of illness and deaths, in teens or adults.
Now, researchers from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and their colleagues have shown that simply changing the dose and route of administration from intradermal (ID) to intravenous (IV) greatly increases the vaccine’s ability to protect rhesus macaques from infection following exposure to Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. The findings provide a new understanding of the mechanisms of BCG-elicited protection against tuberculosis infection and disease. In addition, the findings support investigation of IV BCG administration in clinical trials to determine whether this route improves its effectiveness in teens and adults.
Study investigators at the NIAID Vaccine Research Center were led by Robert A. Seder, M.D., and Mario Roederer, Ph.D. Their collaborators included JoAnne L. Flynn, Ph.D., of University of Pittsburgh School of Medicine.
Three-dimensional PET-CT scans of lungs showing areas of TB infection and tissue inflammation (red and orange) in macaques challenged with Mtb after vaccination with either ID BCG (top row) or IV BCG (bottom). Photo credit: University of Pittsburgh School of Medicine
Monday, December 30, 2019
Latest findings suggest that the chemicals, which are no longer produced in the United States but persist in the environment, may have lasting health effects even at low levels
Pregnant women exposed to persistent organic pollutants, or POPs, had slightly smaller fetuses than women who haven’t been exposed to these chemicals, according to an analysis of ultrasound scans by researchers at the National Institutes of Health and other institutions. The researchers also found that the women in their study had lower levels of POPs than women in the 2003-2004 U.S. Health and Nutrition Survey, the most recent comprehensive study of these compounds in U.S. pregnant women. The latest findings suggest that the chemicals, which are no longer produced in the United States but persist in the environment, may have lasting health effects even at low levels.
The study appears in JAMA Pediatrics and was conducted by Pauline Mendola, Ph.D., an investigator in the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, and colleagues.
Persistent organic pollutants are chemicals once used in agriculture, disease control, manufacturing, and industrial processes. They include the pesticide DDT and dioxin, a byproduct of herbicide production and paper bleaching. POPs are slow to break down, may persist in water and air, and may be passed through the food chain. Their health effects vary, but some compounds have been linked to reproductive disorders and a higher risk of birth defects.
Monday, December 23, 2019
Mutations in the RIPK1 gene responsible for CRIA syndrome
Over the last 20 years, three families have been unsuspectingly linked by an unknown illness. Researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and other organizations have now identified the cause of the illness, a new disease called CRIA syndrome. The results were published in the journal Nature.
NHGRI scientific director Daniel Kastner, M.D., Ph.D., a pioneer in the field of autoinflammatory diseases, and his team discovered CRIA, which has symptoms including fevers, swollen lymph nodes, severe abdominal pain, gastrointestinal problems, headaches and, in some cases, abnormally enlarged spleen and liver.
The disorder has characteristics typical of an autoinflammatory disease, where the immune system appears to be activated without any apparent trigger. Although the condition is not life-threatening, patients have persistent fever and swollen lymph nodes from childhood to old age, as well as other symptoms that can lead to lifelong pain and disability.
Thursday, December 19, 2019
An experimental Zika vaccine lowered levels of virus in pregnant monkeys and improved fetal outcomes in a rhesus macaque model of congenital Zika virus infection, according to a new study in Science Translational Medicine. The research was conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and their collaborators from the University of California, Davis; Duke University, Durham, North Carolina; and the University of California, Los Angeles. NIAID scientists developed the experimental vaccine and currently are evaluating it in a Phase 2 human clinical trial. The vaccine uses a small circular piece of DNA, or plasmid, containing genes that encode Zika virus surface proteins to induce an immune response.
Zika virus is primarily transmitted to humans by Aedes mosquitoes; it also can be transmitted through sex. The virus can cause serious birth defects in babies born to mothers who become infected during pregnancy. Ideally, the authors note, a Zika vaccine would be given to adolescents and adults of childbearing age before pregnancy to prevent congenital Zika syndrome.
Large outbreaks of Zika virus in the Americas in 2015 and 2016 led to thousands of cases of congenital Zika syndrome, prompting NIAID scientists to quickly develop and begin clinical trials of the NIAID DNA Zika vaccine. While clinical trials can yield data on safety and how the vaccine performs in recipients, due to the diminished incidence of Zika, conducting a clinical trial that would determine the vaccine’s ability to prevent adverse fetal outcomes has been logistically difficult. Therefore, researchers developed a macaque model of congenital Zika syndrome to provide another way to evaluate the experimental vaccine.
A vial of the NIAID Zika virus investigational DNA vaccine, taken at the NIAID Vaccine Research Center’s Pilot Plant in Frederick, Maryland.
Wednesday, December 18, 2019
Findings give new insights into the connection between poor air quality, children’s health, and mother’s health
A new report from the National Toxicology Program (NTP) suggests that traffic-related air pollution increases a pregnant woman’s risk for dangerous increases in blood pressure, known as hypertension.
NTP scientists evaluated published research on the link between traffic-related air pollution, or TRAP, and hypertensive disorders broken down by pollutant measurements of TRAP, such as particulate matter (PM2.5). PM is the term for a mixture of solid particles and liquid droplets found in the air, and PM2.5 refers to fine inhalable particles, with diameters that are generally 2.5 micrometers or smaller. The average human hair is about 70 micrometers in diameter, about 30 times larger than the largest fine particle.
“What we found when we reviewed the literature is that exposure to PM2.5 from traffic emissions was associated with development of hypertensive disorders in pregnant women,” said Brandy Beverly, Ph.D., lead scientist and researcher at the National Institute of Environmental Health Sciences, part of the National Institutes of Health. “When these women are exposed to PM2.5 during their entire pregnancy, the likelihood of developing preeclampsia increases by about 50%.”
Monday, December 16, 2019
NEI-led study to test safety of treatment for a form of age-related macular degeneration that currently lacks treatment
Researchers at the National Eye Institute (NEI) are launching a clinical trial to test the safety of a novel patient-specific stem cell-based therapy to treat geographic atrophy, the advanced “dry” form of age-related macular degeneration (AMD), a leading cause of vision loss among people age 65 and older. The geographic atrophy form of AMD currently has no treatment.
“The protocol, which prevented blindness in animal models, is the first clinical trial in the U.S. to use replacement tissues from patient-derived induced pluripotent stem cells (iPSC),” said Kapil Bharti, Ph.D., a senior investigator and head of the NEI Ocular and Stem Cell Translational Research Section. The NEI is part of the National Institutes of Health.
The therapy involves taking a patient’s blood cells and, in a lab, converting them into iPS cells, which have the potential to form any type of cell in the body. The iPS cells are programmed to become retinal pigment epithelial (RPE) cells, the type of cell that dies early in the geographic atrophy stage of macular degeneration. RPE cells nurture photoreceptors, the light-sensing cells in the retina. In geographic atrophy, once RPE cells die, photoreceptors eventually also die, resulting in blindness. The therapy is an attempt to shore up the health of remaining photoreceptors by replacing dying RPE with iPSC-derived RPE.
The researchers will take a patient’s own blood cells, and in a lab, convert them into iPS cells capable of becoming any type of cell in the body. The iPS cells are then programmed to become retinal pigment epithelial cells, the type of cell that dies early in the geographic atrophy form of AMD.
Wednesday, December 11, 2019
NIH study may inform ways to reduce male-to-female HIV transmission
Nano-sized vesicles released by certain bacteria that inhabit the vagina may protect against HIV infection, suggests a study of human cells and tissues by researchers at the National Institutes of Health and the University of Bologna, Italy. Known as extracellular vesicles, these bubble-like particles are produced by many kinds of cells and are thought to transport molecules from one cell to another. The study was led Leonid Margolis, Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in Nature Communications.
The researchers conducted a series of experiments showing that vesicles isolated from four strains of Lactobacillus bacteria interfere with the ability of HIV to infect cells. In one experiment, researchers added vesicles to cultures of immune cells known as T lymphocytes and infected the cultures with HIV. HIV infection in the treated cells was much lower than in the untreated cells. When the researchers increased the quantity of vesicles, a much smaller proportion of cells were infected.
Similarly, treatment with vesicles reduced HIV infection in human lymph and uterine cervix and vaginal tissues. The researchers found that bacterial vesicles suppressed the binding of viruses to the cell surface, an essential step before the virus can infect a cell. Further experiments showed that bacterial vesicles directly affect HIV rather than cells. Exposing the viruses to vesicles reduced the appearance of surface molecules on the virus’ outer covering, which it needs to attach to cells.
Diagram of a bacterial vesicle. Courtesy of the NICHD Section on Intercellular Interactions