It’s Not Just Venus or Mars Anymore

December 5, 2014 by

Dec. 5, 2014

By Medical Discovery News

It's Not Just Mars or Venus Anymore

While the gender gaps are closing, sometimes the differences between men and women seem as great as the differences between Venus and Mars. For example, men and women tolerate medications very differently. Due to this, the Food and Drug Administration (FDA) has recently changed the recommended dosage of the sleep aid Lunesta from two milligrams to one milligram because of its prolonged effects on women.

Women reported feeling drowsy in the morning hours after waking, raising concerns about the hazards of driving and working. While men and women are often prescribed the same dosages of medications, this case shows how men and women are not the same organism and drug dosing might need to take that into consideration.

For basic studies in the biomedical laboratory, many cells lines that are used experimentally are derived from tissues obtained from males, either human or animal. Even in the very early steps of identifying a drug and determining how it works, efforts are already focused on those of us with a Y chromosome.

Clinical trials are conducted before a new drug can be approved, and trials also favor males. In fact, white males remain the predominant subjects for drug trials today. Women were initially avoided in clinical trials because of concerns that they were pregnant or would become pregnant. Women also have cyclic hormones that alter metabolism and could interact with drugs. While this is precisely why women’s tolerance of a drug should be tested prior to its approval, researchers thought this complicated the early stages of the process. Once a drug is launched, the number of people using the drug expands and these side effects start to be reported. While an individual physician may notice patients have side effects, they do not have a wide view of the whole population’s reactions.

Pharmokinetics is the study of what happens to drugs administered to a living organism, and could explain some reasons why men and women handle the same medication differently. For starters, men and women have a number of basic physiological differences. Firstly, women tend to have a lower body weight and body volume. Therefore, the concentration of a drug is often higher in a woman. Women also have a lower gastric emptying, slower gastrointestinal motility, and different absorption rate that can alter the amount of a drug that gets to the blood and is distributed throughout the body. They have different glomerular filtration in their kidneys, which reduces the rate at which drugs are cleared out of the body and therefore leads to higher and more prolonged drug levels. Women experience greater sensitivity to beta blockers, which are used to treat heart conditions; opioids, which are used to control pain; and antipsychotics.

The pharmacodynamics (how drugs function) in female and male bodies can be quite different also. Aspirin is a great example. It is less effective at lowering subsequent heart attacks in women when given the standard preventive dose. They may need higher doses to prevent a second cardiovascular episode.

Recently, the National Institutes of Health (NIH) has required that all cell, animal, and human studies it funds have a balanced representation of both genders. While this may increase the cost of developing therapeutics, it will certainly expand our understanding of how medicines affect the genders differently and improve drugs for everyone.

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Bear-ly Understanding Diabetes

May 30, 2014 by

May 30, 2014

By Medical Discovery News

What can studying grizzly bears reveal about human diabetes?

While they are some of the largest bears on earth, Grizzly bears aren’t usually accused of being fat. Regardless, these animals are helping scientists discover new and better treatments for human obesity and diabetes.

Grizzlies spend the late summers consuming more than 50,000 calories per day. As a comparison, a moderately active 50-year-old human female is recommended 2,300. Grizzlies then hibernate for up to seven months, relying on the pounds of stored fat they accumulated before winter. While hibernating, bears do not eat, urinate, or defecate. 

Scientists wondered if all the weight and fat bears gain results in diabetes like it does in humans. Overweight people face an increased risk of type 2 diabetes, in which the body does not make enough of the hormone insulin or cells do not respond to it. Insulin helps move a type of sugar called glucose from the blood into cells, where it is used for energy and as a precursor for other molecules the body needs. If sugar levels in the blood remain elevated and the body doesn’t have enough insulin, cells are starved for energy, leading to damaged eyes, kidneys, nerves, and hearts. 

Interestingly, Grizzly bears can actually control their insulin responsiveness. When they are the fattest, they are most sensitive to insulin, thereby keeping their blood sugar levels healthy. Soon after going into hibernation, they switch to complete insulin resistance, meaning they develop type 2 diabetes. But unlike humans, their blood sugar levels remain normal. When they awaken in the spring, their insulin responsiveness is restored. Bears do this not so much to regulate their blood sugar levels as to regulate their storage and utilization of fat. So how do bears control their insulin responsiveness? And could it lead to new treatments for type 2 diabetes in humans?

PTEN is a protein that regulates cells’ sensitivity to insulin. Scientists know exactly when Grizzlies increase or decrease PTEN activity, they just don’t know how. People with a PTEN mutation have a metabolism similar to Grizzlies’.  These people have an increased risk of obesity and cancer but a decreased risk of developing type 2 diabetes because they are more sensitive to insulin.

Grizzlies have also evolved to the ability to accumulate large amounts of fat only in their adipose tissue, just below the skin so it doesn’t interfere with the rest of their bodies. In humans, on the other hand, fat can accumulate in many places like the liver, in muscles, and around other internal organs, which are all highly unhealthy places to keep fat. Bears can also have elevated levels of cholesterol without the serious consequences of cardiovascular disease.

During hibernation, the Grizzly bears’ kidneys shut down. But despite the high levels of toxins that accumulate in the blood without working kidneys, they don’t die or even suffer from it like a human would. When they wake up, their kidney function is restored with no permanent damage.

After millions of years of evolution, Grizzly bears and other animals have developed solutions for biological challenges humans still face. Studying them is a new approach that has the potential to create treatments for many human conditions.

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Organ Farming

March 15, 2014 by

March 14, 2014

By Medical Discovery News

Imagine that a patient needs an organ, like an airway to their lungs called a trachea. A scientist harvests some of the patient’s cells and attaches them to a scaffold the proper shape and size for the tube. The cells and scaffolds are placed into a tissue reactor and – ta da! – in a week or two there is an organ ready for the surgeon to transplant into the patient. While it sounds like a chapter from “Brave New World,” this science fiction scenario is a growing reality.

Bladders and ears have been grown in the laboratory, and hearts, eyes, and kidneys and other organs are in progress. These organs are close to the natural ones they’re copying – some even have their own immune system. In April 2013, surgeons at the Children’s Hospital of Illinois implanted a bioengineered trachea into a two-year-old child. This was the first surgery of its kind in the United States and one of only six worldwide.

The patient receiving the transplant was a girl named Hannah Warren who was born without a trachea, commonly called a windpipe. Since birth, she’s had a plastic pipe inserted in her mouth that went down into her lungs, allowing her to breathe. She could not eat normally or even speak. With few options available, this type of congenital defect has always meant an early death; only a few children live past the age of six.  

Bioengineered organs could change that. The key is stem cells – cells that are at an early stage of development and through the influence of their environment can produce the many specialized cells of organs and tissues. In this case, doctors harvested the girl’s immature stem cells from the marrow inside her bones. The stem cells were taken to the lab and allowed to adhere to a plastic fiber model precisely the size (about one-half inch in diameter) and structure of the trachea she needed. Once placed in an incubator called a tissue bioreactor, the stem cells colonized the plastic and started growing. While they were growing, cells communicated with neighboring cells and worked together to produce all the cells needed for a functioning trachea. 

At the end of this process, Dr. Paolo Macchiarini implanted the trachea with promising results. Since the cells in the bioengineered trachea were based on ones from her body, her immune system didn’t recognize it as foreign and reject it, a big worry for transplant recipients. Without a plastic pipe in her mouth, Hannah was able to smile for the first time.

Unfortunately, while her trachea functioned well after the surgery, her esophagus never recovered. She underwent a second surgery to fix her esophagus and died from complications. Macchiarini said that her death was not due to the implanted trachea but her own “very fragile” tissue. He called Hannah a “pioneer” in the field of regenerative medicine and plans to conduct similar operations.

The next step for bioengineered organs is clinical trials leading to Food and Drug Administration approval. This would give more scientists and physicians the opportunity to improve organ “farming” and extend this field into a therapy that could benefit many.

For a link to this story, click here.

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