Discovery may spell cure for heart and lung disease
Last Updated: October 25, 2010 2:56am
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MONTREAL - A Canadian researcher may have discovered a breakthrough diagnosis - even a cure - for a devastating and deadly disease called pulmonary hypertension.
New research indicates a protein, dubbed PIM-1, is high in patients with the condition. The higher the PIM-1 levels, the more severe the patient's pulmonary hypertension, which narrows and scars pulmonary arteries and can stress the heart.
"The PIM-1 level in healthy patients is almost zero," Dr. Sebastien Bonnet, a researcher the Heart and Stroke Foundation, said in an interview Sunday. "Patients with severe pulmonary hypertension have PIM-1 levels through the roof."
Bonnet explained that somehow the protein makes cells sick. The research is ongoing.
"If you're able to knock down the expression of PIM-1, you'll be killing only the cells that are sick without harming the healthy cells," Bonnet said.
His research uncovered something even more exciting: by blocking the harmful protein, researchers were able to reverse the condition.
For the Quebec-based Bonnet, it's a ray of hope for patients struggling with the disease.
"The treatments now are limited and inefficient and the only way to cure someone with pulmonary hypertension is with a heart and lung transplant," he said.
The new discovery also might make it easier to diagnose the condition.
"This could be as simple as a blood test," he said. "You can just check the (PIM-1) levels."
Pre-clinical trials are now underway and Bonnet is optimistic human clinical trials on a drug cure will begin in a year.
According to the Pulmonary Hypertension Association of Canada, up to 5,000 Canadians have been diagnosed with the disease. Another 5,000 Canadians may be living with the illness and unaware they're sick. (torntosun)
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Human lungs have 'taste buds' that can detect bitter substances
By DAILY MAIL REPORTER
Last updated at 9:37 AM on 25th October 2010
Last updated at 9:37 AM on 25th October 2010
Human lungs are able to 'taste' bitter flavours in the same way we taste food with our tongues, scientists have discovered. The taste receptors in the lungs are the same as those in the mouth except they are not found in clusters and do not send any signals to the brain.
The breakthrough discovery could have massive impact on the development of drugs to treat asthma as they discovered that bitter compounds open lung airways far better than current drugs.
Researchers at the University of Maryland School of Medicine in Baltimore found that the lung receptors were limited to bitter tastes and did not include the ability to sense salty, sour, sweet and savoury tastes, which the tongue can detect.
A slide of lung taste receptors through a microscope. The red bands are receptors, blue dots are nuclei. Scientist have discovered that human lungs can detect bitter tastes
The study's senior author, Stephen Liggett, professor of medicine and physiology at the University of Maryland School of Medicine, said: 'The detection of functioning taste receptors on smooth muscle of the bronchus in the lungs was so unexpected that we were at first quite sceptical ourselves.'
Prof Liggett, a pulmonologist, said his team found the taste receptors by accident, during an earlier, unrelated study of human lung muscle receptors that regulate airway contraction and relaxation.
The airways are the pathways that move air in and out of the lungs, one of several critical steps in the process of delivering oxygen to cells throughout the body.
However, in asthma the smooth muscle airways contract or tighten, impeding the flow of air, causing wheezing and shortness of breath.
For the current study, Prof Liggett's team exposed bitter-tasting compounds to human and mouse airways, individual airway smooth muscle cells, and to mice with asthma.
Most plant-based poisons are bitter, so the researchers thought the purpose of the lung's taste receptors was similar to those in the tongue - to warn against poisons.
Prof Liggett said: 'I initially thought the bitter-taste receptors in the lungs would prompt a 'fight or flight' response to a noxious inhalant, causing chest tightness and coughing so you would leave the toxic environment, but that's not what we found.
'There are thousands of compounds that activate the body's bitter taste receptors but are not toxic in appropriate doses.
'Many are synthetic agents, developed for different purposes, and others come from natural origins, such as certain vegetables, flowers, berries and trees.'
The researchers tested a few standard bitter substances known to activate these receptors.
Prof Liggett said: 'It turns out that the bitter compounds worked the opposite way from what we thought. They all opened the airway more profoundly than any known drug that we have for treatment of asthma or chronic obstructive pulmonary disease (COPD).'
Quinine and chloroquine have been used to treat completely different diseases (such as malaria), but are also very bitter. Both of these compounds opened contracted airways profoundly in laboratory models.
Even saccharin, which has a bitter aftertaste, was effective at stimulating these receptors.
Prof Liggett says this observation could have implications for new therapies. He added: 'New drugs to treat asthma, emphysema or chronic bronchitis are needed.
'This could replace or enhance what is now in use, and represents a completely new approach.'
The researchers also found that administration of an aerosolised form of bitter substances relaxed the airways in a mouse model of asthma, showing that they could potentially be an effective treatment for the disease.
However, Prof Liggett warned that eating bitter tasting foods or compounds would not help in the treatment of asthma. He said: 'Based on our research, we think that the best drugs would be chemical modifications of bitter compounds, which would be aerosolised and then inhaled into the lungs with an inhaler.'
Another aspect of the breakthrough was the unexpected role that the mineral calcium plays when the lung's taste receptors are activated.
The study's principal author, Dr Deepak Deshpande, assistant professor of medicine at the University of Maryland School of Medicine and an expert in how calcium controls muscles, said: 'We always assumed that increased calcium in the smooth muscle cell caused it to contract, but we found that bitter compounds increase calcium and cause relaxation of airway muscle in a unique way.
'It appears that these taste receptors are wired to a special pool of calcium that is right at the edge of these cells.'
Dr Albert Reece, vice president for medical affairs at the University of Maryland, said: 'The work of this team exemplifies what it takes to make real improvements in treating certain diseases.
'These researchers were willing to take chances and ask questions about an unlikely concept. Why are taste receptors in the lungs? What do they do? Can we take advantage of them to devise a new therapy? In the end, their discoveries are in the best tradition of scientific research.'
Asthma and COPD together affect 300 million people worldwide. The findings were published online in the journal Nature Medicine.
(dailymail.co.uk)
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