Can sleep deficiency really kill you?

As I have stated before I am one of the unfortunate 64 million people in America that suffer from insomnia. My dad has it, my brother has it, and I have it. Without insomnia I probably wouldn’t get a whole lot of things done (like this blog post). Fortunately for me having insomnia also has some other perks, such as getting to watch TV shows about insomnia. Earlier tonight I watched a show on the National Geographic channel about a form of insomnia that I was completely unaware of and I am sure I am not the only person who is unaware of it since it affects only 40 families in the entire world. This type of insomnia is called Fatal Familial Insomnia or FFI. I never thought that Insomnia could kill someone, but this form of Insomnia makes every person who is diagnosed with it a victim.

I thought that I would go over the sleep cycle a little bit first to help you understand how sleeping works but since a colleague has already posted a blog about it I will just set up a link to that post here http://fourthirstypandas.blogspot.com/2010/04/sweet-dream-or-beautiful-nightmare.html.

FFI has been characterized as a genetic disorder caused by a mutation at codon 178 of the prion protein gene. This is also a problem in the condition called “Mad Cow Disease.” Prions are proteins that attack the nervous system and cause the symptoms associated with “Mad Cow Disease.” In FFI the cause of the prion protein is genetic, where a single base pair is coded incorrectly. This is one of 3 billion base pairs known in the human genome. In FFI the prions accumulate in the Thalamus in the brain. The Thalamus was never thought to control sleep, but it does transmit signals to the cortex of the brain. In patients with FFI lesions occurred in the Thalamus and the Cortex of the brain. With FFI 90% of the neurons in the Thalamus have disappeared.

ally sleep has been one of the hardest things to study, but some recent studies using a PET scan and a tagged amino acid may give us some clues as to why we need to sleep. One of the theories is that we need sleep to repair proteins in the cells of the brain, which can’t happen while we are awake because the brain is too busy and has too many processes happening. During a normal day while we are awake we accumulate adenosine in our brain, which signals our bodies to sleep. Sleep would eliminate the adenosine and produce more proteins for repair of the brain cells.

Humans have varying levels of sleep, but so do many animals in nature. A normal human gets somewhere between 7 and 8 hours of sleep per night, but an animal such as a lion gets up to 15 hours a day. A elephant on the other hand gets around 4 hours of sleep. One of the theories about this is that predator species can sleep more because they don’t generally have many predators, while the prey species get much less sleep so they can evade their predators. But what if we could sleep and be awake at the same time. I know this sound ridiculous, but a few animals in nature already have achieved this process. If we could somehow find out how to translate this to humans we could eliminate FFI and other sleep associated disorders.

One of the species in nature that sleeps all the time but we never see it are dolphins. I always think of a dolphin as an animal that is always moving and swimming. A study done in San Diego evaluated if a dolphin lost any mental abilities when forced to stay alert for multiple days. The dolphin was trained to detect a swimmer that was in the bay while the dolphin was detained in a fenced area. When the dolphin detected the swimmer it hit a switch on the dock. The dolphin showed no decline in activity and detected every time the swimmer was in the bay. The dolphin slept throughout the entire experiment. This is possible due to dolphins having something called unihemispheric sleep. Throughout the dolphins life one half of their brain is active while the other is sleeping and then they switch. Another animal that is theorized to do this is many different avian species. Studies have shown that they can sleep while also watching for predators while they are on land, but it is still unclear wheather they can sleep while flying.

So far for all terrestrial mammals, sleep is needed. After several days of sleep deprivation there is a drastic decrease in overall health. One side effect is diabetes, due to insulin resistance that is accumulated. There is also a decrease in lymphocytes which fight bacterial infections in the body. In most mammals if sleep is deprived for 2 weeks death will occur. In patients with FFI death usually occurs from 7 to 36 months, and the unfortunate thing is that once symptoms of FFI start they never go away until the patient dies. The unfortunate thing about this disease is that there is currently no cure. And if one family member is ever diagnosed with FFI there is a 50% chance that their children will be diagnosed with it as well since it is a dominant gene.

So now that I have accumulated a massive amount of adenosine in my brain I think I will go sleep and I encourage everybody else to get sufficient amounts of sleep as well.

References:

1. National Geographic Explorer: “Fatal Insomnia”, aired April 27, 2010

2. Fatal familial insomnia: clinical features and molecular genetics; PIETRO CORTELLI, PIERLUIGI GAMBETTI, PASQUALE MONTAGNA and ELIO LUGARESI; J. Sleep Res. (1999) 8, Suppl. 1, 23-29; European Sleep Research Society

3. Montagna P, Gambetti P, Cortelli P, Lugaresi E (2003). "Familial and sporadic fatal insomnia". Lancet Neurol 2 (3): 167–76. doi:10.1016/S1474-4422(03)00323-5

4. Almer G, Hainfellner JA, Brücke T, et al. (1999). "Fatal familial insomnia: a new Austrian family". Brain 122 ( Pt 1): 5–16. doi:10.1093/brain/122.1.5.

Are tanning beds a cancer risk?

Being the scrawny white nerd that I am, I don’t tan… I burn. This concerned me greatly since I would soon be traveling to the Outer Banks in my Marine Biology class. I wanted to go swimming in the ocean, but that would mean my un-tanned, blinding white-ness would be on display. Not wanting to look completely ridiculous, I contemplated going tanning for the first time ever.

But I was worried. Tanning lotions were out because I don’t like the thought of smearing skin-altering chemicals on myself. And I had heard from many sources that tanning beds cause cancer. So I decided to look into the matter.

According to this study I found [1], exposure to tanning beds actually does increase the risk of developing malignant melanoma (skin cancer).

Where are they getting that from?
Ting and his crew wanted to test the hypothesis that increased exposure to tanning beds was linked to an increased risk of developing malignant melanoma.

To perform the study, surveys were completed by a random sample of 551 patients. The surveys asked questions like:

1. Extent of tanning bed exposure (how much of the body was exposed to the tanning bed),
2. use in the last 12 months (number of tanning sessions in the past year),
3. age at first exposure,
4. season of use (when in the year do they go tanning?),
5. lifetime number of tanning sessions,
6. minutes spent per session,
7. sun protection attitudes and practices (do they usually wear sunscreen?), and
8. leisure and occupational sun exposure (how often are they exposed to natural sunlight?).

The survey also looked at demographic information, such as:

• Gender,
• age,
• race,
• tendency to tan,
• level of education,
• work environment (indoor or outdoor),
• number of sunburns in the past, and
• previous history of various cancers.

Here is a look at the demographic information.

When doing a scientific study, you must always be wary of confounding variables (also known in statistics as a lurking variable). A confounding variable is any variable other than the independent variable that may bear any effect on the behavior of the subject being studied.
An example of a lurking variable would be testing infant memory with a matching game, but waiting too long between tests so that improved results on the second game may be due to the baby’s brain developing and not the baby’s memory. (Wikipedia)

The study took into account confounding variables such as:

• Indoor vs. outdoor occupation and leisure activities,
• Fitzpatrick skin type (numeric scale for skin color),
• history of blistering sunburn, and
• use of sunscreen and sun protective clothing.

If a patient had a family history of malignant melanoma, he was not assessed because of the potential for inaccuracy. (If their family is genetically more likely to get skin cancer without ever having used a tanning bed, than if they use tanning beds and get cancer it is impossible to determine the cause of the cancer.)

The answers to the survey were compared to those patients’ medical records. Of the 501 records available, 194 of the patients had been diagnosed with some kind of skin cancer (see Table 1).

Tables 2 and 3 below show the data that links exposure to tanning beds and risk for developing malignant melanoma.  Click on them to make them larger.

“Most modern tanning units produce mainly UV-A and less than 5% UV-B, although this amount of UV-B irradiation exceeds that in natural sunlight, and is sufficient to cause immunosuppression.” [1]
Ummm…yikes.

Interestingly, (according to Ting) this was the first study that accounted for confounding factors, and considered the frequency or duration of tanning bed exposure.
Yeah, that might help.

After they did a bunch of calculations that I won’t go into, they found that their hypothesis was correct. Increased exposure to tanning beds increased the risk of developing malignant melanoma.
Most of the patients that went tanning the most were young women under 45 years old, which meant that they were at the greatest risk of developing skin cancer.


Since exposure to tanning beds would increase my risk for developing cancer, I guess I better find a safer way to get a tan.
Of course, all of this is a moot point now that I’m already back from our OBX trip.
And yes, I did get sunburned after only an hour of kayaking.



[1]
Ting, W., Schultz, K., Cac, N. N., Peterson, M., & Walling, H. W. (2007). Tanning bed exposure increases the risk of malignant melanoma. International Journal of Dermatology, 46(12), 1253-1257.

DOI: 10.1111/j.1365-4632.2007.03408.x

Journal article LINK

Preventing Parasitic Infection

Nearly one third of the people that will die this year will die from an Infectious disease worldwide. So what exactly is an Infectious disease? An infectious disease is an illness derived from a pathogenic microbe. A pathogenic microbe can range from bacteria, a virus, a fungus, or a parasite. Current research is focused on preventative and medicinal treatments that can attack the microbe before it can invade the host body. One way a drug can disrupt the microbe from invading the host cell is to use small-molecules to prevent the pathogen from invading the host cell.

Invading pathogens have proteins on their outer shell that can be used to identify the pathogen or the proteins can be used to attach to a host cell. These proteins can also be used to locate and disable a foreign microbe from invading your body. This study focuses on identifying small-molecules that can disrupt the ability of a certain pathogen, Toxoplasma gondii. T. gondii is the causative agent in toxoplasmosis, and is related to Plasmodium which causes malaria.  ¹Toxoplasmosis is a parasite that can infect humans, but is transmitted to humans by the common housecat.  ²People and animals can become infected by being exposed to contaminated meat, fecal matter of an infected cat, or from a mother to her fetus. Roughly one third of the world is estimated to be carrying the Toxoplasma parasite. Symptoms of infection are mild flu like symptoms. However, if you have a weakened Immune System or are pregnant, the infection may cause more serious symptoms such as swelling of the brain and neurological disease, or it can be fatal especially to the fetus.

T. gondii has two distinct phases in its lifecycle. The first phase is the sexual stage. The sexual stage takes place in humans and in cats, the pathogen invades a cell and produce bradyzoites (form of the pathogen).  Bradyzoites most commonly found in muscle or in the brain, are continually being produced until the host cell bursts from the infection. The burst cell releases the replicated bradyzoites which are now called tachyzoites.  Tachyzoites are the mobile form of the pathogen that can infect new cells or pass into the small intestine. The tachyzoites can be killed off by the host immune system once the host cell has burst. However, if the tachyzoites reach the small intestine, the tachyzoites produce oocytes which get excreted in fecal matter. The production of the oocytes is the sexual phase of the T. gondii life cycle. The shed oocytes can then be passed onto humans by consuming unwashed vegetables or eating infected meat.

The molecular mechanism by which T. gondii invades cell is still unknown, but is crucial to survival of the pathogen. Although the ³mechanism by which cells are invaded isn’t known, it is known that small-molecules can inhibit the invasion of host cells by the parasite T. gondii. The current experiment tested 12,160 small molecules for their ability to prevent the pathogen from invading cells. The experiment was carried out by placing equal amounts of the differing small-molecules into wells with possible host cells and one invading parasite (T. gondii) and one non-invasive parasite. The invasive T. gondii pathogens were labeled with a yellow fluorescent protein that allows the parasite to be visualized using a microscope. The effectiveness of the small-molecules on preventing the Toxoplasma pathogen from invading host cells was determined visually by looking to see if any Toxoplasma pathogens made it into the cell. If yellow specks were seen in the cell, the cell was invaded by the pathogen and the small-molecule did not prevent the pathogen from entering the cell.

Of the 12,160 small-molecules tested, only twenty-four molecules non-cytotoxic prevented invasion by the Toxoplasma parasite. After identifying the twenty-four inhibitory small-molecules, nineteen of the small-molecules effects could be reversed. That leaves five small-molecules that cause irreversible effects to the Toxoplasma pathogen.  

The twenty-four small molecules were then examined to determine how they exerted their effects on the parasite.  There are five ways that the parasite can be inhibited, but only three were examined. The first mechanism studied was the motility of the Toxoplasma pathogen. Of the 24 inhibitory molecules, 21 prevented the parasite from becoming mobile by inhibiting slime trail formation which helps the parasite glide across a surface. A second mechanism that was studied was the formation of a conoid extension. A conoid extension extends and retracts repeatedly as the parasite moves across a cell. None of the inhibitory small-molecules caused a conoid extension, while three inhibited extension but did not affect motility of the parasite. The final mechanism studied was the secretion of microneme. Micronemes are secretory organelles that help the parasite attach to the host cell.  18 of the 24 small-molecules inhibited the secretion of a certain microneme protein. However, the effect of inhibiting microneme protein secretion on parasite-host relationships was not studied.

The study found 24 out of 12,160 small molecules inhibited the invasion of T. gondii into a host cell.  The 24 molecules that inhibited invasion of a pathogen into a host cell can be used to study how the parasite infects the host cell. Further characterization of the inhibitory molecules can be used to help determine how each of the molecules prevents the invasion into a host cell. By studying Toxoplasma gondii, the molecular mechanism by which the parasite infects cells can be studied. By identifying the mechanism of invasion, further infections of the Toxoplasma pathogen and other pathogens related to it can be prevented.

¹http://en.wikipedia.org/wiki/T._gondii  

²http://en.wikipedia.org/wiki/Toxoplasmosis

³Carey, K et al. “A Small-Molecule approach to studying invasive mechanisms of Toxoplasma gondii.” Proceedings of the National Academy of Sciences in the United States of America. Doi. 10.1073