World AIDS Day

Today is World AIDS Day.This day is dedicated to raising awareness of the AIDS pandemic, caused by the infection of the HIV virus. I found an interesting blog titled “A generation free of AIDS?” (http://www.huffingtonpost.com/zp-heller/a-generation-free-of-aids_b_2220140.html) and it summarizes the newest statistical reports about AIDS in the world submitted by UNAIDS.

UNAIDS is an organization assigned to serve as the advocate for global action against HIV and AIDS. Their efforts are aimed to prevent the spread of HIV, and to provide care and support for those infected and to provide support for the families with affected patient.

According to UNAIDS the rate of new HIV infections has been reduced by more than 50% in adults (15-49 years) in 25 countries between 2001 and 2011.Furtheremore, the number of people dying from AIDS-related causes began to decline in the mid-2000s because of scaled up antiretroviral therapy and the steady decline in HIV incidence since the peak of the epidemic in 1997.

There is no current cure for AIDS, however, there are a variety of drugs that can be used in combination to control the virus. Usually when the diagnosis occurs, treatment is a combination of at least three of the following drugs to protect against drug immunity. The following treatments are available to control the AIDS pandemic:

1.      Non-nucleoside reverse transcriptase inhibitors

2.      Nucleoside reverse transcriptase inhibitors.

3.      Protease inhibitors

4.      Entry or fusion inhibitors

5.      Integrase inhibitors.

 The main goal of the campaign is to achieve an AIDS free generation by 2015 by increasing prevention, and increasing the funding that goes into developing new and more efficient drugs that combat the virus and its changing strains. However,  UNAIDS Executive Director Michel Sidibé has warned caution when looking at the promising numbers because much more can be done to achieve this goal. We are still seeing the HIV/AIDS epidemic rise in countries where prevention and education is not as prevalent as in the developing countries, and now the sub-Saharan countries. According to Sidibé, there are still socio-economic gaps among the countries that are mostly affected by AIDS, and we must continue to fight against the disease by increasing knowledge about prevention and funding to AIDS/HIV research programs.

The UNAIDS Report can be found at :

http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2012/JC2434_WorldAIDSday_results_en.pdf

Changing The Cancer Game - Promising New Technology From SomaLogic

At the cancer symposium in Ireland, there were many companies promoting their products, from new drug therapies to improved imaging technologies. The only company that I thought was truly revolutionary was SomaLogic, and they are actually based in our very own Boulder, Colorado.

Traditionally, physicians and scientists use antibodies to identify proteins of interest, these antibodies run into issues of specificity, they are expensive to produce, and most importantly – it is too expensive for researchers to use more than one antibody at a time, and way too time consuming to do a complete proteomic analysis of a tumor sample. Imagine a cost-effective way to have a complete proteomic profile of a tumor sample in just one procedure. That’s what SomaLogic has done. By combining a CGH array and modified DNA aptamers to sample a tumor tissues’ proteomic profile.  

Aptamers are peptide or nucleotide sequences that bind to specific molecules. SomaLogic has taken DNA and modified their bases to increase their binding affinity. These Slow Off-rate Modified Aptamers, or simply SOMAmers, bind to proteins like antibodies. They are very specific and very tiny, easily able to bind both intracellular and extracellular proteins. The advantage of this is that unlike antibodies, you can easily sequence DNA. After SOMAmers bind to their specific proteins, they are washed off and put into an array. From here it is like array CGH, except it is now for protein expression. If tumor samples overexpress a certain protein, it will more likely bind to the oligomers in the array plate, where their copy numbers will be detected. Each plate will have hundreds of wells, each containing a specific sequence for a SOMAmer. This way, in one array, you can get a complete proteomic read on a tumor tissue to understand what proteins are over- or under-expressed, and thus, much easier to identify where the problem is in a patient’s cellular pathway. If the thought of DNA binding to protein hasn't blown you away yet, there is more good news. Since it’s just modified DNA, SOMAmers can be produced very quickly and cheaply by PCR. On top of all this, we now know that there are free-floating tumor cells in the blood stream of cancer patients, but antibodies are often not specific enough to be used diagnostically in those samples. SOMAmers however, are able to identify the proteomics of those cells. Although more verification needs to be done, and more research is needed to identify what the complete proteomic profile actually means for personalized treatment, this technology is potentially a huge step towards early cancer screening, diagnosis, and drug targeting.

Citations:

Gold L, Ayers D, Bertino J, Bock C, Bock A, et al. (2010) Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery. PLoS ONE 5(12): e15004. doi:10.1371/journal.pone.0015004

Kraemer S, Vaught JD, Bock C, Gold L, Katilius E, et al. (2011) From SOMAmer-Based Biomarker Discovery to Diagnostic and Clinical Applications: A SOMAmer-Based, Streamlined Multiplex Proteomic Assay. PLoS ONE 6(10): e26332. doi:10.1371/journal.pone.0026332

Young Blood

Today’s society is obsessed with being young.   However, the best option for remaining young appears to be calorie restriction.   Problem is few want to do this, and calorie restriction is not 100% proven to work in humans. Really the best people can do right now is just cover aging up is by moisturizing, using sunblock, working out, getting botox or dying our hair.  But, two classic experiments have kept many hopes alive to turning back the clock someday.

Back in 1989 two scientist, Faulkner and Carlson, at the University of Michigan performed a muscle graft experiment.  Muscle from a young rat was grafted and put into an old rat. Then vice versa, old rat muscle placed into a young rat.  To the scientist surprise the old muscle grafted into the young rat regenerated much better than the young muscle grafted into an old mouse.  This changed the idea of aging to focus on the environment of the tissue.  

Well, sixteen years later in 2005, Thomas Rando at Stanford University performed a similar experiment where they changed the systemic environment of an old mouse. Rando’s lab did this by a cool technique called parabiosis where two mice's cardiovascular systems are surgically connected together. Rando specific technique used was called Heterchronic Parabiosis (i.e. Different Age Parabiosis) to assess how a young systemic environment affected an older animal. He connected the circulatory system of an old mouse to a young mouse.  Similar to Faulkner and Carlson’s muscle graft experiment, the older mice tissue showed a youthful regeneration. 

Both of these studies indicate that the blood or the systemic environment that the tissue baths in plays a key role in the aging process. While, the age of the tissue seems to have less of an impact.  The future of these experiments could lead to organ regeneration or  celebrities like Suzan Summers getting blood transfusion from babies to roll back the odometer.  The world of aging might have cracked the code and  it appears the to be something in young blood. Vampires might have had it right this whole time. 

References:

Carlson, B. M., Dedkov, E. I., Borisov, A. B., & Faulkner, J. A. (2001). Skeletal Muscle Regeneration in Very Old Rats. The Journals of Gerontology Series a: Biological Sciences and Medical Sciences, 56(5), B224–B233. doi:10.1093/gerona/56.5.B224

Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433(7027), 760–764. doi:10.1038/nature03260

The Physiological Effects of Grief

Grieving

           

            I thought I should write a blog about what my life consists of now and before I was in this program. A death of a person very close to you changes not only your life but changes you. As many say who have lost someone close to them, a piece of you died with the person who died. Now, especially with the lost of a partner, you have to figure out who you are again without that person, on top of dealing with the physical and mental effects of grief.

What is grieving? Grieving is a process a person goes through when they have lost someone they cared for, the closer that person was to them, the harder to deal with the grief it becomes. 

Stages of Grieving

·       Linear model (after the person dies): denial, anger, bargaining, depression, and acceptance. In this model a person moves from one stage to the next. But every person is different and every loss is different therefore the linear model is not completely accurate.
·       Dr. Barbara Okun and Dr. Joseph Nowinski model (this begins before the person dies)

o   Crisis- Family life is changed by the diagnosis and a lot of feelings like anger and guilt or sadness are felt.

o   Unity- People now put the patient's needs before theirs.

o   Upheaval- The patient maybe in remission or doing well and now its time for the family to discuss how the illness has been affecting them.

o   Resolution- The patient’s health deteriorates and now it is time to accept death is imminent. Major decisions for hospice and end-of-life matters must be discussed, resolving issues with the patient happen during this time as well.

o   Renewal-Begins with the funeral and continues as people adjust to life without the patient or the patient's needs.

·       Grieving is different for every person, especially depending on the circumstances associated with the loss.

o   A loss after a long illness is a relief to those that loved that person and not as much of a shock, they started dealing with the death long before the death occurred. Their shock was in the initial stages of diagnosis.

o   A sudden lost is dramatically different. The world has changed in one moment and the shock lasts much longer.

Effects of Grieving- This can last anywhere from a week to years depending on the person.

·      Nervous System- The body sends powerful stress response in the body and induces a 'flight or fight' system in the body. The heart beats faster and increase in blood pressure, even if the person seems to not move, inside their body is in turmoil. The person is on edge and has difficulty making decisions because the brain is purely focusing on survival. 
·      Immune System - Bereavement causes a fall in activity of the T-lymphocytes, which allow more minor infections or colds. Pre-existing painful problems may get worse and other chronic health conditions often flare up too. This partly explains why people who experience personal loss are at higher risk of dying during the first year.
·       Physical/Mental-Depression can disrupt sleep and appetite, and cause the body to slow down. Anxiety can cause a racing pulse, hot sweats, poor sleep and loss of appetite. The grieving can also turn to alcohol, recreational drugs or prescription drugs during this time, which could cause a lot of problems. People who have lost a partner can sometimes clearly see or hear the person about the house even converse with them at length. As well as flashbacks of how the person died, these are very intense in the first month while the brain is processing what has happened. The person has difficulty with even the simplest of tasks like bathing and eating because every part of their body is grieving which is absolutely exhausting and requires a lot of energy.  

References:

http://web.ebscohost.com.dml.regis.edu/ehost/pdfviewer/pdfviewer?sid=56eef0d2-5359-4373-9c37-83654c4fa34e%40sessionmgr114&vid=7&hid=119

http://www.bbc.co.uk/health/emotional_health/bereavement/bereavement_physical.shtml

Who needs eyes when you have a tongue?

After reading Haley’s blog post about the monkey that could control a robotic hand with nothing more than neural activity, it reminded me of a phenomenon I had learned about in undergrad.  Using the same principle of a human-machine interface, but utilizing the sensory system, researchers have been able to restore some level of sight in blind individuals.  We all remember learning in Physiology that as long as downstream neurons are being stimulated, you will still perceive senses, even if the primary transducing neuron is damaged or absent entirely – A behavior exemplified by phantom limb pain.  Interestingly enough, the current standard for vision replacement does not attempt to recreate visual pathways, but instead relies on crossmodal activation of the primary visual cortex. 

The technique involves placing a camera in a pair of glasses worn by the blind individual.  This camera is attached to a grid of electrodes that is placed somewhere on the body, most frequently on the tongue (for its high level of acuity).  The live feed from the camera causes the electrodes to stimulate mechanoreceptors on the tongue.  

As with any physical stimulation of the tongue, this signal is then sent to the thalamus, where the amazing happens – the signal gets routed to the primary visual cortex!  This physical stimulation is actually allowing the blind people to “see”!  A recent study used fMRI to determine whether pathways downstream of the primary visual cortex are maintained as well, and they found that both the dorsal and ventral stream (the two primary pathways leading from the occipital lobe responsible for location and identification respectively) are being recruited just as it would be in an individual with normal vision (Ptito et al., 2012).  Unfortunately, the Tongue Display Unit (TDU) is not powerful enough to replicate vision entirely.  Functionally, utilization of the TDU allows blind individuals to see large shapes and it helps them navigate around obstacles, but not too much beyond that so further research is necessary.  Additionally, only blindness resulting from damage upstream of the occipital lobe and thalamus can be treated by such a device.

Alternatively, a recent review suggested bypassing the tongue entirely.  They propose that implantation of electrodes into the lateral geniculate nucleus of the thalamus could do the trick (Pezaris et al., 2009).  This technique, known as deep brain stimulation, is used to treat other problems like Parkinson’s and major depression.  Preliminary animal models for the technique show promising results! 

1. Ptito, M., Matteau, I., Wang, A. Z., Paulson, O. B., Slebner, H. R., Kupers, R. (2012).  "Crossmodal Recruitment of the Ventral Visual Stream in Congenital Blindness." Neural Plasticity, 2012, 1-9.  doi 10.1155/2012/304045.
2. Pezaris, J. S. and Eskandar, E. N. (2009).  "Getting signals into the brain: visual prosthetics through thalamic microstimulation." Neurosurg Focus, 27(1) 1-20. doi:10.3171/2009.4.FOCUS0986.
3. Scott, R.  (2011).  "The injured eye."  Philosophical transactions of the royal society, 366, 251-260. doi:10.1098/rstb.2010.0234

A typical Thanksgiving of turkey, football, and sleep

With Thanksgiving in the rear view mirror, some of us are just starting to wake up from our turkey feast-induced coma. Upon waking from my own Rip Van Winkle caliber nap, I began to wonder why exactly the chemical tryptophan, commonly found in turkey meat, was able to put half of America to bed early last night. In the late 1970's researchers hypothesized that normal dietary doses of tryptophan could be used to treat mild insomnia. To test this hypothesis, they gave their subjects a dose of 1 gram of tryptophan, which is on the high side of normal with respect to dietary intake of tyrptophan in a given meal, and they then measured the time it took for the subjects to fall asleep. This time frame is called the sleep latency period. It was seen that in these mildly insomniac patients, the tryptophan helped them fall asleep 15 minutes earlier on average. It was also shown to help to patients stay asleep longer (Hartmann et al., 1979). Yet the question still remaind how exactly tyrptophan accomplished all of this.

 As it turns out, tryptophan is an important ingredient in making some of the hormones that our central nervous system uses to regulate sleep cycles. When tryptophan passes the blood-brain barrier and enters the cerebrospinal fluid surrounding our brains, it gets converted into the chemical signal serotonin. From this stage, serotonin is transported to a different region of the brain where it is converted into the hormone melatonin (Dulce Favacho de Oliveira Torres et. al., 2009). Among many other functions, melatonin is responsible for lowering body temperature and controlling normal sleep cycles, also known as the circadian rhythm. While this cascade explains how thryptophan can lead to drowsiness, that is only half of the story.

Currently, there is an ongoing debate as to whether it is the tryptophan in the turkey or the sheer quantity of food that is consumed during Thanksgiving meals that contributes to the tired feeling. Many scientists, including the Mythbusters, believe that the large portions and all of the carbohydrates in the meals are responsible for making causing the eater to become drowsy. The large amounts of the hormone insulin that are released after a large meal signals muscle cells to begin taking some amino acids out of the blood to be stored for later while allowing other amino acids, tryptophan included, to stay in the blood stream. The increased concentration of tryptophan relative to the amino acids that are taken out of the blood by the muscles allows tryptophan to find free amino acid transporters in the blood-brain barrier more easily (Wurtman et. al, 2003). As a result, more tryptophan is delivered to the brain and more melatonin is made. From these two pathways, it can be concluded that you should pass on seconds of turkey and all of those carbohydrates if you want to be awake to see the end of the night game next Thanksgiving.

References:
Dulce Favacho de, J., & de Souza Pereira, R. (2010, October 6). Which is the best choice for gastroesophageal disorders: Melatonin or proton pump inhibitors? World Journal of Gastrointestinal Pharmacology and Therapeutics, 1(15), 102-106. 

Hartmann, E., & Spinweber, C. L. (1979, August). Sleep induced by L-tryptophan. Effect of dosages within the normal dietary intake. Journal of Nervous and Mental Disorders, 167(8), 497-499.

Wurtman, R. J., Wurthman, J. J., Regan, M. M., McDermott, J. M., Tsay, R. H., & Breu, J. J. (2003,  January). Effects of Normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. The American Journal of Clinical Nutrition, 77(1), 128-132. 

The Unexpected Danger of Ice Cubes

I recently came across an article that told the story of two siblings who are allergic to the cold, literally!  At first, I was drawn to the article because I have never heard of this type of allergy before, but as I continued to read, I realized how devastating and challenging it is for those with this condition to live normal lives.  These siblings have a rare condition called cold urticaria that only affects one in 100,000 people.  The cause may be extra sensitive skin receptors due to an inherited trait, or certain autoimmune diseases, infections, or a side effect of a medication.  Several genetic mutations are currently under investigation, including deletions in the PLCG2 gene, which regulates elements of the phospholipase-c signaling pathway (Ombrello, 2012).  This pathway activates second messenger molecules that alter various cell responses, such as cell proliferation and differentiation.  The exact mechanism of this pathway in cold urticaria and the cause in general is unclear, though, which makes diagnosis and treatment very difficult.    

Symptoms include hives, itchiness, rash, swelling of the area of contact, and in severe cases, life-threatening anaphylaxis.  Some reactions can be especially dangerous if there is full skin exposure to cold, such as swimming in cold water.  These symptoms are caused by mast cell degranulation, and in the case of severe reactions, large amounts of histamine are released and can cause a sudden drop in blood pressure that can ultimately lead to fainting, shock, or death.

A reaction typically occurs when there is exposure to temperatures below 40 F, but it is harder to escape the cold than you may think.  Some unexpected triggers of cold urticaria include cold countertops, holding a chilled coke can, popsicles, walking barefoot on hardwood floors, and even “running and getting sweaty against the air” (Elaridi, 2012).  The “ice cube test” is used to diagnose cold urticaria by placing an ice cube on the patient’s forearm for 10 minutes, and waiting for a hive or swelling to appear after about 5 minutes after the ice cube is removed (indicating a positive test). 

A positive ice cube test (http://www.nejm.org/doi/full/10.1056/NEJMicm072431)

There are several different forms of cold urticaria that do not have a positive ice cube test, including:  delayed cold urticaria (symptoms occur 12-48 hours of cold exposure), cold-dependent dermatographism (symptoms only occur with pressure on cold skin), cold-induced cholinergic urticaria (symptoms occur with exercise in cold environments), and localized cold reflex urticaria (symptoms occur away from area of direct cold exposure).  A disease called cholinergic urticaria is caused by opposite conditions, where heat exposure causes similar symptoms.  This variation in symptom onset and location greatly contributes to the difficult diagnosis of this disease. 

            There is no cure for this condition, but symptoms can be treated with strong antihistamine medications.  The main course of treatment for these patients is to avoid cold exposure, but for the siblings in the article who happen to live in Colorado, this will be an even greater challenge. 

References:

Elaridi, F. (2012, November 15). Kids Allergic to the Cold - Literally. ABC News. Retrieved November 21, 2012, from http://gma.yahoo.com/blogs/abc-blogs/kids-allergic-cold-literally-203616484--abc-news-health.html.

Ombrello, M., Remmers, E., Sun, G., & Freeman, A. (2012). Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. The New England Journal of Medicine, 366, 330-338.