Red blood cells sense low oxygen in the brain.


When the brain runs low on oxygen, red blood cells sense the deficit and hurl themselves through capillaries to deliver their cargo. That reaction, described online August 4 in Neuron, suggests that red blood cells can both detect and remedy low oxygen.

images of blood cells in capillaries

When researchers stimulated the feet of mice, nerve cells fired off signals in the corresponding part of the brain, depleting that area’s oxygen. Red blood cells in capillaries picked up their speed in response. And in artificial capillaries, the lower the oxygen, the faster the red blood cells moved, Jiandi Wan of the Rochester Institute of Technology in New York and colleagues found. That swiftness was caused by the cells becoming more flexible, a bendiness that let them squeeze through narrow capillaries faster. When researchers stiffened red blood cells with a chemical, the effect of low oxygen on speed disappeared.

The results reinforce the complex and important role of blood in the brain. The findings might ultimately be relevant for disorders in which the link between neural activity and blood flow is damaged, including Alzheimer’s disease, says study coauthor Maiken Nedergaard of the University of Rochester Medical Center.

Scientists discover an enzyme that can change a person’s blood type


Scientists have discovered that a particular type of enzyme can cut away antigens in blood types A and B, to make them more like Type O – considered the ‘universal’ blood type, because it’s the only type that can be donated to anyone without the risk of provoking a life-threatening immune response.

The team, from the University of British Columbia of Canada, worked with a family of enzymes called 98 glycoside hydrolase, extracted from a strain of Streptococcus pneumoniae. Over many generations, they were able to engineer a super high-powered enzyme strain that can very effectively snip away blood antigens where previous generations of the enzyme struggled. “A major limitation has always been the efficiency of the enzymes,” one of the team, Stephen Withers, said in a press release. “Impractically large amounts of enzyme were needed.”

Getting the right type of blood when you need it is crucial, and it has to do with the different types of residue that can accumulate the surface of red blood cells. Both blood types A and B have this residue – A has an N-acetylgalactosamine residue, and B has a galactose residue – and Type AB has a mixture of both. Only Blood Type O is free from this residue, which means it can be received by any patient, no matter what type they’re carrying.

Withers and his team managed to create their ‘mutant’ enzyme strain using a technology called directed evolution, which allows them to insert many different types of mutations into the gene that codes for it, and by progressively selecting strains that are the best at snipping away the blood antigens, were able to create an enzyme that’s 170 times more effective at it than its parent strain. They published their results in the Journal of the American Chemical Society.

“The concept is not new, but until now we needed so much of the enzyme to make it work that it was impractical,” said Withers. “Now I’m confident that we can take this a whole lot further.”

While the current enzyme strain is not yet capable of removing 100 percent of the antigens from Blood Types A and B, which is where it needs to get if the researchers want to make any real use of it, the team is confident that they’ll get it there so they can try it out in clinical trials. Even the smallest amount of antigen in donated blood can set off a dangerous immune response in the recipient.

“Given our success so far, we are optimistic that this will work,” says Withers.

Old Red Cells Still OK in Cardiac Surgery


Transfusing red blood cells that have been stored for 21 days or more does not increase the risk of complications following cardiac surgery, according to a new U.S. trial involving more than 1,000 patients.

“It really doesn’t look like it makes much difference clinically,” said the chief author, Dr. Marie Steiner, a professor of pediatrics at the University of Minnesota. She told Reuters Health in a phone interview that the findings will probably put “a significant damper” on people pushing for fresher blood in such instances.

Previous studies looking at whether older cells posed a risk have produced conflicting results. The new research, known as RECESS and published in the April 9 New England Journal of Medicine, is the first large prospective multi-center study to examine the question in cardiac patients.

It comes on the heels of the larger ABLE study, reported by the Journal last month, which showed no benefit for fresher blood among intensive care patients.

“It’s reassuring,” said Dr. Dean Ferguson, a senior scientist at The Ottawa Hospital in Canada and a coauthor of the ABLE study, who was also involved in an earlier test of new versus old blood in premature infants that produced the same result.

“So now there are three major studies showing no difference,” he told Reuters Health.

Concern about stored blood has been around for nearly two decades.

“It’s a major issue for the blood providers because a lot of the observational work, less rigorous research and animal studies were showing that fresh was better,” said Dr. Ferguson. “They’ve been feeling that pressure for the last few years. That’s why these large trials are needed and helpful. The fact that there’s absolutely no difference is a relief for them.”

All of the 1,098 patients in the new study, from 33 U.S. hospitals, were age 12 and older. Among those who got a transfusion, the median number of units transfused was three.

Half the patients were randomly assigned to receive blood stored for 10 days or less, while the rest received units stored for at least 21 days.

“In the United States, the average storage duration of transfused red cells is 17.9 days,” the researchers said.

To assess any potential impact, they looked for a change in the Multiple Organ Dysfunction Score (MODS) from before surgery at the seventh postoperative day. Patients who died during that period received a maximum score of 24.

 The short-term-storage group, with a mean storage time of 7.8 days, had an 8.5-point change in their MODS scores versus a change of 8.7 in the group with a mean storage time of 28.3 days (P=0.44).

Among the components making up the MODS score, only the hepatic component, which uses total serum bilirubin, showed a significant difference between the groups (P<0.001). “This finding is not unexpected, because red cells hemolyze during storage,” the researchers note.

When they excluded patients who had received a unit that was older or newer than they had been assigned to receive, the outcome scores were still comparable.

Mortality rates were essentially the same — 15 died in the short-term-storage group (2.8%) versus 11 in the long-term group (2.0%) (P=0.43).

On average, people in both groups suffered 1.6 severe adverse events (p=0.75).

Only when it came to a hepatobiliary disorder was a different rate seen, with 5% in the short-term storage group having the problem versus 9% in the long-term group (P=0.02).

“This finding was due entirely to the fact that fewer participants in the shorter-term storage group had hyperbilirubinemia,” the researchers said.

So when it comes to the idea that fresher blood will give better outcomes, Dr. Steiner said, “it surely looks like it ought to be this way in the lab and in dogs, but if you look at the question in a large group of people, it just isn’t that important.”

“My bias is that there’s so much else going (in trauma and cardiac cases) on that the contribution of the red cells is probably not that much,” she said. “You’re talking about people who have been hit by a truck or are having their chest split open. You ask how can one or two units of blood make that much difference. It probably doesn’t.”

The trial was funded by the National Heart, Lung, and Blood Institute.

SOURCE: N Engl J Med 2015

Promising compound rapidly eliminates malaria parasite


A promising anti-malarial compound tricks the immune system to rapidly destroy red blood cells infected with the malaria parasite but leave healthy cells unharmed, an international group of researchers has found. Planning has begun for safety trials of the compound in healthy adults.
A new report says that the rapid action of (+)-SJ733 will likely slow malaria drug resistance.

An international research collaborative has determined that a promising anti-malarial compound tricks the immune system to rapidly destroy red blood cells infected with the malaria parasite but leave healthy cells unharmed. St. Jude Children’s Research Hospital scientists led the study, which appears in the current online early edition of the Proceedings of the National Academy of Sciences (PNAS).

The compound, (+)-SJ733, was developed from a molecule identified in a previous St. Jude-led study that helped to jumpstart worldwide anti-malarial drug development efforts. Malaria is caused by a parasite spread through the bite of an infected mosquito. The disease remains a major health threat to more than half the world’s population, particularly children. The World Health Organization estimates that in Africa a child dies of malaria every minute.

In this study, researchers determined that (+)-SJ733 uses a novel mechanism to kill the parasite by recruiting the immune system to eliminate malaria-infected red blood cells. In a mouse model of malaria, a single dose of (+)-SJ733 killed 80 percent of malaria parasites within 24 hours. After 48 hours the parasite was undetectable.

Planning has begun for safety trials of the compound in healthy adults.

Laboratory evidence suggests that the compound’s speed and mode of action work together to slow and suppress development of drug-resistant parasites. Drug resistance has long undermined efforts to treat and block malaria transmission.

“Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose,” said corresponding author R. Kiplin Guy, Ph.D., chair of the St. Jude Department of Chemical Biology and Therapeutics. “These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world’s children, who are central to the mission of St. Jude.”

Whole genome sequencing of the Plasmodium falciparum, the deadliest of the malaria parasites, revealed that (+)-SJ733 disrupted activity of the ATP4 protein in the parasites. The protein functions as a pump that the parasites depend on to maintain the proper sodium balance by removing excess sodium.

The sequencing effort was led by co-author Joseph DeRisi, Ph.D., a Howard Hughes Medical Institute investigator and chair of the University of California, San Francisco Department of Biochemistry and Biophysics. Investigators used the laboratory technique to determine the makeup of the DNA molecule in different strains of the malaria parasite.

Researchers showed that inhibiting ATP4 triggered a series of changes in malaria-infected red blood cells that marked them for destruction by the immune system. The infected cells changed shape and shrank in size. They also became more rigid and exhibited other alterations typical of aging red blood cells. The immune system responded using the same mechanism the body relies on to rid itself of aging red blood cells.

Another promising class of antimalarial compounds triggered the same changes in red blood cells infected with the malaria parasite, researchers reported. The drugs, called spiroindolones, also target the ATP4 protein. The drugs include NITD246, which is already in clinical trials for treatment of malaria. Those trials involve investigators at other institutions.

“The data suggest that compounds targeting ATP4 induce physical changes in the infected red blood cells that allow the immune system or erythrocyte quality control mechanisms to recognize and rapidly eliminate infected cells,” DeRisi said. “This rapid clearance response depends on the presence of both the parasite and the investigational drug. That is important because it leaves uninfected red blood cells, also known as erythrocytes, unharmed.”

Laboratory evidence also suggests that the mechanism will slow and suppress development of drug-resistant strains of the parasite, researchers said.

Planning has begun to move (+)-SJ733 from the laboratory into the clinic beginning with a safety study of the drug in healthy adults. The drug development effort is being led by a consortium that includes scientists at St. Jude, the Swiss-based non-profit Medicines for Malaria Venture and Eisai Co., a Japanese pharmaceutical company

6 Ways Blood Type Can Influence Personal Health: From Mild Stress To Cancer


bloodBlood type is one of the body’s more mysterious taxonomies. There are four bins our blood call fall into — A, B, AB, and O — and together they represent the four groups of antigens found on the surfaces of red blood cells. But they don’ t just signal who we can donate to and receive from; our blood types can reveal complex patterns of personal health. Here are six to consider:

1. Memory Problems

At-risk: AB

Your brain and vascular system have more in common than you may think. A recent study found people with type AB blood were 82 percent more likely to experience difficulties with memory recall, language, and attention than people with other types. One reason, researchers suspect, is due to the key clotting protein, known as coagulation factor VIII, which may actually reduce the quality of blood flow to the brain, rather than sealing up injury sites.

“Since factor VIII levels are closely linked to blood type, this may be one causal connection between blood type and cognitive impairment,” said Mary Cushman, author of the recent study, to Yahoo Health.

2. Pancreatic Cancer

At-risk: Non-O

It may be more accurate to say people with type O blood are at a lower risk for pancreatic cancer, given the work researchers from Yale University are doing on bacterial infection. In a study conducted last July, scientists from the University’s Cancer Center looked at cases of a common species of bacteria calledHelicobacter pylori, or H. pylori, that lives in people’s gut.

They found people with H. pylori were significantly more likely to develop pancreatic cancer, due to the way A and B antigens help the bacteria thrive. People with type O blood carry no antigens on the surface of their red blood cells. This is what allows them to donate to anyone.

3. Heart Disease

At-risk: AB

A 2012 study from Harvard University found people with non-O blood also happen to have an increased risk for cardiovascular disease. But those with type AB blood were the most at-risk overall, demonstrating a 23 percent greater chance of suffering from heart disease than type O subjects.

Study author Dr. Lu Qi, an assistant professor in the Department of Nutrition, said the particular makeup of people’s antigens should be given the same weight we already assign to cholesterol and blood pressure. “While people cannot change their blood type, our findings may help physicians better understand who is at risk for developing heart disease,” Qi said in a statement.

4. Stress

At-risk: A

Because certain blood types are more likely to co-occur with varying levels of hormones in the body, physicians commonly tailor their exercise recommendations to the patient’s type. People with type A blood, for example, are more likely to have higher levels of cortisol, the stress hormone, in their body. So, stress-reducing exercises, like Tai Chi and yoga, may be more beneficial at cutting that tension than running or weightlifting alone.

When the adrenal gland dumps more and more cortisol into the blood, people’s stress response grows more acute. People with type A blood may find themselves getting anxious more quickly and having a harder time letting troubles roll off their back.

5. Exercise Demands

More generally, the makeup of a person’s antigens on his or her red blood cells can determine how much of a certain hormone gets released. People with type A and B blood respond better to calming, low-intensity exercise like yoga, especially if depression runs in the family. Likewise, people with AB blood benefit from well-rounded workouts that keep their immune systems in check. Type O people, however, are a different story.

“Type O’s are more prone to problems that arise from an inability to clear stress hormones from their system quickly,” Dr. Ginger Nash, a naturopathic physician, told Personalized Living. “It takes more to get a Type O stressed but it takes more to de-stress them as well.”

6. Gut Bacteria

In addition to living on your red blood cells, antigens are often found in the lining of your digestive tract — about 80 percent of people fall into this category. Much of the bacteria living in people’s gut uses these antigens as food, which largely determines which bacteria flourish and which disappear. Prior research has estimated, for instance, that people with type B blood contain up to 50,000 times the number of strains of friendly bacteria than people with either type A or O blood.

“Increasingly, studies are showing that changes in the microflora content of the digestive tract can be linked to metabolic illnesses, including type II (adult onset) diabetes and obesity,” wrote Dr. Peter D’Adamo, physician and author of Eat Right 4 Your Type, in a blog post. “Blood group and secretor status play an important role in conditioning the overall characteristics of the digestive tract.”

Why Can’t You Use Blood from Someone Who Has a Different Blood Type Than You?


Story at-a-glance
• Everyone has one of four blood types – A, B, AB, or O – which is inherited from your parents
• Your blood type is determined by the presence or absence of two antigens – A and B – on the surface of red blood cells. A third antigen, called Rh factor, will either be present or absent, making your blood type positive or negative
• If incompatible blood types are given during a transfusion, the donor cells will be attacked by the patient’s immune system, which may cause shock, kidney failure, and death
• Everyone can receive type O blood, the most common type in the US, as it has neither A nor B antigens on red cells

Everyone has one of four blood types – A, B, AB, or O – which is inherited from your parents, like your eye color, dimples, or curly hair. While all blood is similar in its components (such as containing red cells, platelets, and plasma), it also has important characteristics that make it unique.
Your blood type is determined by the presence or absence of two antigens – A and B – on the surface of red blood cells. A third antigen, called Rh factor, will either be present or absent. Antigens are substances that may trigger an immune response, causing your body to launch an attack if it believes they are foreign.
Taken together, these factors determine the right type of blood for your body, should you need a transfusion. Receiving the wrong type can be catastrophic, even resulting in death. According to Blood Transfusions and the Immune System:1
“If incompatible blood is given in a transfusion, the donor cells are treated as if they were foreign invaders, and the patient’s immune system attacks them accordingly.
Not only is the blood transfusion rendered useless, but a potentially massive activation of the immune system and clotting system can cause shock, kidney failure, circulatory collapse, and death.”
What Exactly Is Blood?
Blood is a living tissue made up of red blood cells, white blood cells, platelets, and plasma (which is more than 90 percent water). Your body weight is about seven percent blood. Men have about 12 pints of blood in their body while women have about nine.2

Blood’s main role is to transport oxygen throughout your body, although it also plays a role in fighting off infections and carrying waste out of your cells. Blood also:3

Regulates your body’s acidity (pH) levels Regulates your body temperature (increased blood flow to an area adds warmth)
Supplies essential nutrients, such as glucose and amino acids, to cells Has specialized cells that promote blood clotting if you are bleeding
Transports hormones Has “hydraulic functions,” helping men to maintain an erection, for instance
Which Blood Types Are Compatible?
It’s not entirely true that you can’t use blood from someone who has a different blood type than you. Everyone can receive type O blood, the most common type in the US, as it has neither A nor B antigens on red cells (and both A and B antibody in the plasma).
Beyond that, however, blood types must be carefully matched as follows to avoid potentially deadly consequences. First, a breakdown of the four blood types:4
• Type A: Only the A antigen on red cells (B antibody in the plasma). The second most common blood type.
• Type B: Only the B antigen on red cells (and A antibody in the plasma). Relatively rare, especially among Hispanics and Caucasians.
• Type AB: Both A and B antigens on red cells (both A and B antibody in the plasma). Very uncommon, only seven percent of Asians, four percent of African Americans, four percent of Caucasians, and two percent of Hispanics have this blood type.
• Type O: Neither A nor B antigens on red cells (both A and B antibody in the plasma). The most common blood type, especially among Hispanics.
Your blood type may be either positive or negative, depending on the presence or absence of Rh factor (about 85 percent of people are Rh positive). Generally, Rh negative blood is given to Rh-negative patients while those with Rh positive blood receive Rh positive blood in transfusions.
Rh factor is generally tested during pregnancy, as an incompatibility between mother and fetus may cause the mother’s body to attack the baby’s “foreign” blood. (Rh immune globulin is an effective treatment that can stop this attack if found early on.)
The American Red Cross has created the following chart to explain which blood types are compatible with others.

Source: American Red Cross, Blood Types
Why Are There Different Blood Types?
It’s thought that different blood types developed as a way to help protect humans from infectious disease. For instance, cells infected with malaria don’t “stick” as well to type O or type B blood cells, which means a person with type O blood may get less sick if they’re infected with malaria than someone with a different blood type.

Perhaps not coincidentally, regions with high burdens of malaria, such as Africa, also have a high rate of type O blood. The fact that certain blood types are incompatible is likely the result of a mutation. As reported by Live Science:5
“Blood type A is the most ancient, and it existed before the human species evolved from its hominid ancestors. Type B is thought to have originated some 3.5 million years ago, from a genetic mutation that modified one of the sugars that sit on the surface of red blood cells. Starting about 2.5 million years ago, mutations occurred that rendered that sugar gene inactive, creating type O, which has neither the A nor B version of the sugar.

And then there is AB, which is covered with both A and B sugars. …But incompatibility is not part of the reason humans have blood types, says Harvey Klein, chief of transfusion medicine at the National Institutes of Health Clinical Center. ‘Blood transfusion is a recent phenomenon (hundreds of years, not millions), and therefore had nothing to do with the evolution of blood groups,’ he said.”
Does Your Blood Type Dictate Your Diet?
You may have heard about diets based on your blood type, which claim that certain foods react in different ways in your body depending on your blood type. I personally do not advocate such diets. I actually attended a small lecture given by Dr. D’Adamo before he published his book Eat Right for Your Type. I believe one of the main reasons why most support it is due to the fact that O is the most common blood type and calls for a severe grain restriction. If you are a blood type A like myself, it can lead to severe problems.
I actually developed diabetes after following it for a short time. My fasting blood sugar shot up to 126. Not only did it include eating large amounts of fruit for breakfast, but advocated mild exercising for blood type A. So, I cut down my exercise and increased my fruit intake, which resulted in a 20-pound weight gain and a diagnosis of diabetes. This is one of the reasons I am so passionate about my nutrition plan – it is based on whole foods, nothing too extreme, and goes by the guiding principle to listen to your body and let it be your guide on which foods are best for you.
Facts About Donating Blood
Someone in the US needs blood every two seconds,6 so if you’re up for doing a good deed, donating blood is a phenomenal choice. More than 41,000 blood donations are needed each day, but although about 38 percent of Americans are eligible to donate blood, less than 10 percent actually do so each year.7 The two most common reasons why people don’t donate blood are fear of needles or simply not thinking about it.
On the other hand, those who choose to donate most often do so in order to help others (which it does in spades, as one donation may save the lives of up to three people). So, if you can spare an hour or so of your time, your donated blood may save the life of someone in an emergency (or the countless other scenarios in which blood transfusions are necessary). Finally, if youriron levels are high, donating your blood is a safe, effective, and inexpensive solution, as one of the best ways you can get rid of excess iron is by bleeding.

 

Microparticles Deliver Oxygen.


Researchers have developed fast-dissolving particles that may one day prevent organ damage or death by instantly infusing oxygen into the blood.

Scientists have crafted an injectable foam containing oxygen-carrying microparticles that could potentially be used to resuscitate patients undergoing severe oxygen deprivation. The team of researchers, most of whom work at Children’s Hospital Boston, demonstrated that the microparticle solution could rapidly oxygenate the blood of rabbits struggling to breath in low oxygen conditions. They report their findings in the latest issue of Science Translational Medicine.

“This is a potential breakthrough,” Peter Laussen, cardiac intensive care doctor at Children’s Hospital Boston who was not involved in the work, told ScienceNOW. “You can apply this across healthcare, from the battlefield to the emergency room, intensive care unit, or operating room.”

A body deprived of oxygen is a body in trouble. When major organs like the brain and heart don’t receive an adequate supply of oxygen they falter and fail, sometimes in minutes. Traditionally, physicians used therapies such as CPR and tracheal intubation, where a breathing tube ventilates the lungs after being inserted into a patient’s windpipe, to deliver fresh oxygen to the bloodstream of a person in the midst of a medical emergency.

The microparticles, which consist of spherical shells of lipids surrounding a small bubble of oxygen gas, deliver oxygen almost immediately to red blood cells in a way that is safer and more rapid than currently used methods. The research team, led by Children’s Hospital Boston cardiologist John Kheir, found that the solution could completely saturate red blood cells in oxygen-deprived rabbits within seconds of injection, and they kept rabbits with totally blocked airways alive for 15 minutes using the oxygen-infused microparticles. “Essentially as soon as we started injecting it, clinically we started to see an effect,” Kheir told ScienceNOW.

Researchers are now testing the microparticle solution on large animals, and if those and later human clinical trials are successful, the therapy could make its way into the clinic or other emergency situations. “This is still in its infancy,” Laussen added, “but this idea of a new and novel way to effectively deliver oxygen is, I think, very exciting.”

Sedimented_red_blood_cells

Source: http://www.the-scientist.com