How a Heart Fails

July 12, 2015 by

July 10, 2015

By Medical Discovery News

A heart

What exactly causes a heart to fail? It may come down to a simple protein, which scientists recently identified as having an important role in how a heart goes from weakening to failing.

Your heart is a strong, muscular pump slightly larger than your fist that pushes blood through your body. Blood delivers the necessary oxygen and nutrients to all cells in all the organs. Every minute, your heart pumps five quarts of blood. Human hearts have four chambers: two atria on top and two ventricles on bottom. Oxygenated blood leaves the lungs, enters the left atrium, moves to the left ventricle, and is then pumped out of the heart to the rest of the body. After it circulates, blood returns to the heart, enters the right atrium, moves to the right ventricle, and is then sent back to the lungs for a fresh dose of oxygen. Although your heart beats 100,000 times each day, the four chambers must go through a series of highly organized contractions to accomplish this.

Any disruption of this process can have serious consequences such as heart failure, which is clinically defined as a chronic, progressive weakening of the heart’s ability to circulate enough blood to meet the body’s demands. To compensate, the heart enlarges, which increases contractions and the volume of blood pumped. Blood vessels elsewhere in the body narrow to keep blood pressure normal. Blood can even be diverted from less important organs, ensuring more vital organs like the brain and heart are satisfied. However, such responses mask the underlying problem: the weakening heart, which continues to worsen. Ultimately, the body can no longer compensate for the heart, which is when it will start to fail.

Scientists at the University of California, San Diego School of Medicine studied the cellular changes in weakened hearts to better understand the transition from the compensatory stage, when it works harder to pump blood, to the decompensation, when it fails to pump blood sufficiently. They were especially interested in a RNA-processing protein called RBFox2 because it is involved in the heart’s early development and its continuing functions. When genes are expressed, DNA is transcribed into RNA, which is then processed and eventually used to make proteins such as RBFox2.

Sure enough, levels of RBFox2 were dramatically reduced in the hearts of mice with a condition similar to heart failure. Then they genetically engineered mice without RBFox2, which developed symptoms of heart failure. Not only are low levels of this protein connected to weakened heart muscle, without enough of it, the body cannot compensate and the heart declines more quickly. However, we still don’t know why levels of RBFox2 decline during the transition to the decompensatory phase of heart failure.

In the future, this research might be used to develop treatments that reverse the decline of RBFox2 and effectively slow or prevent heart failure.

For a link to this story, click here.

Filed Under: Health Tagged With: , , , , , , , , , , , , ,

The Altitude Gene, A Denisovan Gift

January 27, 2015 by

Jan. 23, 2015

By Medical Discovery News

Altitude Gene, A Denisovan Gift

Those traveling to the Himalayas have a tough time adjusting to the harsh altitude. But for those native to Tibet, called the Roof of the World due its location 14,700 feet up, it’s not a problem. That’s because Tibetans have adapted to this harsh environment partly due to a gene they inherited from an extinct species of prehumans called the Denisovans.

Anyone traveling to high altitudes like those in Tibet can get altitude sickness and there is no way to predict who will get it. The severity of it varies according to genetics and the rate of ascent, but it is not influenced by age, gender, physical fitness, or previous altitude experience. Symptoms can include headaches, nausea, dizziness, fatigue, shortness of breath, loss of appetite, and disturbed sleep. Severe symptoms could indicate high altitude cerebral edema, which impairs brain function, progresses rapidly, and can become life-threatening in a matter of hours.

However, Tibetans live at these extreme altitudes without developing these problems. So how did they adapt to such a challenging environment?

Studies have linked the Tibetan’s adaptation to high altitude with several genes, including a unique form of the EXPAS1 gene. This gene responds to low oxygen levels to increase hemoglobin production. However, Tibetans with this gene do not have elevated levels of hemoglobin. This seems counterintuitive, since increasing hemoglobin could increase the amount of oxygen being transported in the blood. This would be advantageous at altitudes where the availability of oxygen is reduced, which then limits the uptake of oxygen in the lungs. On the other hand, increasing red blood cells would also thicken the blood, making it less efficient in distributing oxygen and increasing the risk of stroke. The Tibetan variant of EXPAS1 gene might then be protective, but we don’t know how exactly it works.

We know that the ancestors of Nepal’s Sherpa people carried the Tibetan EXPAS1 gene variant about 30,000 years ago. Today, only Tibetans carry this version of the gene, no other modern humans have it. New data suggests it may have come from an extinct population of prehuman called the Denisovans. So far they have only been found in a cave in the Altai Mountains in southern Siberia in East Central Asia. More proof is needed to eliminate another extinct species, the Neanderthals, who also have a version of EXPAS1 similar to the Tibetan one. This is another example of genes acquired by interbreeding between Homo sapiens and other ancient species. About 5 percent of the genetic information of Australasians is shared with Denisovans, while 2.5 percent of human DNA originates from Neanderthals. Modern humans have bits of DNA from these ancient species that have made important contributions to the success of our genome.

For a link to this story, click here.

Filed Under: Health Tagged With: , , , , , , , , , , , ,

Artificial Blood

November 12, 2014 by

Nov. 7, 2014

By Medical Discovery News

Red blood cells

In the series “True Blood,” the invention of artificial blood allows vampires to live among humans without inciting fear. In the real world, however, artificial blood would have very different effects, as 85 million units of blood are donated worldwide and there is always a demand for more. An artificial blood substitute free of infectious agents that could be stored at room temperature and used on anyone regardless of blood type would be revolutionary.

That is exactly what a group of scientists at the University of Essex in England are working on, although the search for an artificial blood substitute started 80 years ago. All red blood cells contain a molecule called hemoglobin, which acquires oxygen from the lungs and distributes it to cells throughout the body. Their plan is to make an artificial hemoglobin-based oxygen carrier (HBOC) that could be used in place of blood.

HBOCs are created using hemoglobin molecules derived from a variety of sources, including expired human blood, human placentas, cow blood, and genetically engineered bacteria. The problem is that free hemoglobin, which exists outside the protective environment of red blood cells, breaks down quickly and is quite toxic. Therefore, HBOCs are not approved for use in most of the world due to their ineffectiveness and toxicity.

The active group in hemoglobin that binds to oxygen is called heme, which can actually be quite toxic. Scientists have found a variety of ways to modify hemoglobin to increase its stability but safety issues still remain. If the hemoglobin’s processing system is overwhelmed, a person may develop jaundice, which causes the skin and whites of the eyes to turn yellow. Too much free hemoglobin can also cause serious liver and kidney damage. When free hemoglobins, not whole red blood cells, are infused, the human body’s natural system for dealing and disposing of this molecule is overwhelmed, leading to toxicity. That is why blood substitutes consisting of free hemoglobin have been plagued with problems, such as an increase in deaths and heart attacks.

But scientists involved in this latest effort to produce a blood substitute have been reengineering the hemoglobin molecule. They are introducing specific amino acids, which are the building blocks of proteins, into hemoglobin in an effort to detoxify it. Preliminary results indicate that this approach may work. They have already created some hemoglobin molecules that are much less reactive and are predicted to be less toxic when used in animals or people.

If successful, this HBOC would be a universal product, meaning it could be used on everyone and there would be no need to waste time on testing for blood types. It would also be sterile, free of any of the infectious agents that donated blood must be tested for. Instead of refrigeration, it could have a long shelf life at room temperature, perhaps years, so it could be stockpiled in case of major emergencies. It could even be kept on board ambulances and at remote locations far from hospitals. The search for an effective and nontoxic blood substitute is one the medical field’s Holy Grails, and if proven successful, these scientists may have finally found it.

For a link to this story, click here.

Filed Under: Health Tagged With: , , , , , , , , , , , , , , , ,

Hope for Sickle Cell

September 20, 2014 by

Sept. 19, 2014

By Medical Discovery News

While sickle cell disease has long been studied, a recent discovery revealed that the disease significantly increases the levels of a molecule called sphingosine-1-phosphate (S1P), which is generated by an enzyme called sphingosine kinase 1 (SphK1). Inhibiting the enzyme SphK1 was found to reduce the severity of sickle cell disease in mice, which will hopefully lead to new drugs that target SphK1in order to treat sickle cell disease in humans.

Sickle cell disease is caused by a change in the gene that is responsible for a type of hemoglobin, the protein molecule in red blood cells that carries oxygen. This tiny change results in hemoglobin clumping together, changing the shape of red blood cells.

The name for sickle cell disease actually comes from misshapen red blood cells. Rather than being shaped like a disk, or a donut without a whole, sickle cells are shaped like a crescent, sort of bending over on themselves. The normal shape is critical to red blood cells’ ability to easily travel through blood vessels and deliver oxygen to cells and tissues. Sickle cells become inflexible and stick to each other, blocking the flow of blood through blood vessels.

Symptoms of the disease begin to appear at about four months of age. Normally, red blood cells live for about 120 days. Sickle cells only survive 10-20 days. Although the bone marrow tries to compensate for the rapid loss of red blood cells, it cannot keep up. The disease causes pain, anemia, organ damage, and possibly infections.

Although the symptoms and their severity vary, most people with sickle cell disease will have periodic crises lasting hours or days. Symptoms include fatigue, paleness, shortness of breath, increased heart rate, jaundice, and pain. Long-term damage can occur in the spleen, eyes, and other organs, and sickle cell disease increases the risk of stroke. People who only inherit one copy of the sickle cell hemoglobin gene have a milder case of the disease than those who inherit two copies, one from each parent.

Current treatments only reduce the number and the severity of crises using hydroxyrurea, blood transfusions, pain medications, and antibiotics. As the disease advances, dialysis, kidney transplants, eye surgeries, gall bladder removal, and other treatments may be necessary. The only cure for the disease is a bone marrow transplant, which is not an option for everyone.

So it’s pretty exciting that when scientists found that levels of S1P were elevated in mice with sickle cell disease, they inhibited the enzyme SphK1 to reduce the levels of S1P. As a result, red blood cells lived longer and had less sickling. The mice also had less inflammation and tissue damage, which would reduce damage to red blood cells and prevent symptoms of the disease. When they engineered sickle cell disease mice without the gene for the enzyme SphK1 that makes S1P, again the mice had less sickling and symptoms.

How does S1P influence sickling? Apparently, it binds directly to hemoglobin and reduces its ability to collect and carry oxygen, which causes the characteristic folding of cells. S1P has other roles in the body, so it is unknown whether inhibitors to SphK1 can safely and effectively be used in humans to treat sickle cell disease.

For a link to this story, click here.

Filed Under: Health Tagged With: , , , , , , , , , , , , , , , , , , , ,

High Altitude Sickness

June 21, 2013 by

June 21, 2013

By Medical Discovery News

For those visiting Denver or other mile-high cities, the incredible panoramic views may be overshadowed by headaches that worsen with higher altitudes. Such headaches are a common symptom of altitude sickness, but it is impossible to predict who will react to high altitudes and the severity of those symptoms. And now, research shows that serious altitude sickness may result in long-term brain damage.

Contrary to popular belief, the concentration of oxygen at higher altitudes is the same as sea level, about 21 percent. But the atmospheric pressure changes significantly, from 760 millimeters of mercury at sea level to only 410 millimeters of mercury at the top of Longs Peak in the Rocky Mountains. That 46 percent drop in pressure allows oxygen molecules to be spaced farther apart in the air. As a result, a person breathes in fewer oxygen molecules in each breath.

To compensate, the body breathes faster to take in more oxygen molecules and maintain blood oxygen levels. But this adjustment generally takes one to three days, which explains why the No. 1 cause of altitude sickness is going too high too fast. Then the body can’t keep healthy oxygen levels and the amount of oxygen in the body lowers, called hypoxia. This can cause fluid to leak from small blood vessels called capillaries and accumulate in the lungs and the brain. While some cases of altitude sickness end with headaches, the added stress on the lungs, heart, and arteries can lead to serious consequences, including death.

When fluid continues to leak into the brain, an incredibly dangerous condition known as high altitude cerebral edema (HACE) can develop. Symptoms include inhibited mental function, hallucinations, loss of coordination, impaired speech, personality changes, nausea, and coma. The only treatment options are to move the person to lower altitude (10,000 feet or less) or put them in a high-oxygen hyperbaric chamber. Doctors used to believe that once treated, patients fully recovered.

However, a new study looked at brain scans of 36 mountain climbers and found several small blood vessels leaking into brain tissue in eight of the 10 climbers with earlier cases of HACE. Only two of the other 26 climbers without previous case of HACE had similar leaks, called microhemorrhages. This shows that a person’s chance of developing mircohemorrages probably increases with HACE. The severity of the hemorrhages correlated to the severity of the climber’s HACE. It’s unclear if more time in high altitudes affects the lesions or what their long-term consequences may be.

Earlier studies showed that almost every MRI of a Mt. Everest climber showed evidence of brain damage. Even amateur climbers, climbers of lesser altitudes, and climbers with no symptoms of altitude sickness showed some sign of brain damage. The damage was still evident years later, even if the climber no longer went to high altitudes.

This recent finding has raised many questions; for example, do HACE victims have an increased incidence of developing dementia or other neurological disorders?  More studies are necessary to verify the results of long-term changes to the brain as a result of high altitudes and HACE. Mountain climbers need to be aware of these risks before they pursue that next peak.

For a link to this story, click here.

Filed Under: Uncategorized Tagged With: , , , , , , ,