Study breathes new life into fight against primary killer of premature infants
These microscopic images of lung tissue from newborn mice show a cross section of the alveoli, the buds in lungs where air exchange takes place. The air sacs (white) in the alveoli on the left, which were taken from a normal mouse, have expanded fully, indicating the animal could breath normally. Those on the right have failed to expand, because the mouse suffered from a new respiratory syndrome discovered by Salk scientists. Credit: Courtesy of Salk Institute for Biological Studies
A discovery by scientists at the Salk Institute for Biological Studies might explain why some premature infants fail to respond to existing treatments for a deadly respiratory distress syndrome (RDS) and offers clues for new ways to treat the breathing disorder.
The scientists identified a new form of RDS in newborn mice and traced the problem to a cellular receptor for thyroid hormone, a key player in many developmental processes in the body. They found that two drugs used for treating overactive thyroid glands saved mice with a deadly genetic alteration that mimicked the newly discovered lung problem.
"We've added a piece of the puzzle that had been missing for decades," says Ronald Evans, a Howard Hughes Medical Institute Investigator and the March of Dimes Chair in Developmental and Molecular Biology at Salk. "This gives us an entirely new avenue for explaining and treating RDS and other respiratory problems that occur in infants."
RDS affects about one percent of infants born in the United States and is the leading cause of death among premature babies. The disease occurs because the infants' lungs are not yet fully developed at birth and lack a slippery substance called surfactant, which is necessary for the lungs to inflate with air.
To encourage the lungs to develop faster and produce the surfactant, doctors treat many expecting mothers and premature infants with glucocorticoids, steroid drugs that speed maturation of surfactant-producing cells, known as type 2 pneumocytes.
In some cases, however, infants fail to respond to the steroid treatment, and die from the respiratory syndrome, which suggests that some other biological mechanism might be at work.
To explain this, the Salk researchers turned their attention to another type of cell lining the lungs, type 1 pneumocytes, flat cells that allow air exchange between the blood stream and the lung's interior.
"We knew that both types of cells, type 1 and type 2 pneumocytes, would be important for lung development, " says Liming Pei, a postdoctoral research associate who led the project. "While a lot is known about type 2 cells, the type 1 cell is poorly understood."
The researchers developed a strain of mice in which they disrupted the ability of type 1 pneumocytes to respond normally to thyroid hormone, which prevented the cells from maturing.
Unlike type 2 pneumocytes, which mature rapidly in infants given steroid hormone, the type 1 cells failed to respond to steroid treatment and the mice died due to the inability of their lungs to function.
However, mice treated with the medications propylthiouracil or methimazole, normally given to people with thyroid disease, recovered from the disorder and their type 1 cells matured normally.
"This might explain why some infants don't respond to steroid treatment, which only targets the type 2 pneumocytes," Evans says. "There may be an entirely different underlying problem than what the doctor is treating."
The findings identify cell sensors (called thyroid hormone receptors) that help type 1 pneumocytes mature and suggest that drugs controlling this hormone could help premature infants' lungs function earlier.
The genetic make up of mice and humans is very similar, so the researchers are optimistic that their findings will eventually lead to new treatments for infants with RDS. "These mechanisms could also play a role healing lung tissues," Pei says. "They might help older children and adults who have suffered lung damage from flu, asthma, emphysema or other types of respiratory disorders."
He cautioned, however, that the thyroid drugs used in the study are only approved for adults, and that their use in infants would have to be explored with caution. However, because their properties are well known there is clear potential for their use in infants.
The findings of the research, which was funded by the Francis Family Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, the March of Dimes and the National Institutes of Health, was published yesterday in Nature Medicine.
Provided by Salk Institute
- Scientists show gene mutation may cause immature lungs in newborns Nov 24, 2008 | not rated yet | 0
- Drug therapy for premature infants destroys brain cells in mice Nov 17, 2008 | not rated yet | 0
- Findings suggest optimal oxygen dose for preterm infants Jun 02, 2010 | not rated yet | 0
- Experimental stem cell treatment arrests acute lung injury in mice Feb 03, 2010 | not rated yet | 0
- Estrogen activates critical lung genes to improve lung function following preterm birth Mar 12, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | 5 / 5 (1) | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | 3 / 5 (1) | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
22 hours ago | 5 / 5 (6) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
22 hours ago | 5 / 5 (1) | 1
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
14 hours ago | not rated yet | 1
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
May 20, 2013 | 4.8 / 5 (31) | 9 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
May 22, 2013 | 4.3 / 5 (6) | 6 |
Salamanders' immune systems are key to their remarkable ability to regrow limbs, and could also underpin their ability to regenerate spinal cords, brain tissue and even parts of their hearts, scientists have ...
May 20, 2013 | 4.9 / 5 (7) | 5 |