Beneficial Biochemical Consequences of Excercise

When we go for a physical, doctors will often tell us to exercise more.  We all know exercise is good for us; it promotes healthy blood pressure, can help lower high cholesterol, stave off obesity, and the many associated diseases from obesity.  It can help us to fight cancer and keep the germs at bay.  But have you ever wondered why exercise is so good?  We know the positive effects of exercising, but we may not know the causes behind the benefits.

It is known that obesity leads to many diseases through a chronic low-level exposure of pro-inflammatory signals.  The fat cells themselves pump out compounds known as adipokines.  These adipokines can lead to the increased concentrations of pro-inflammatory compounds in the body such as IL-6, TNFa, and C-reactive protein.  In addition, fat cells can recruit certain immune cells that will increase the amount of inflammation.

A strong immune system is necessary for survival, however if the immune system is too strong or is always in an active state, it will lead to collateral damage within the body.  This damage can lead to several major diseases including cancer.  A consistent exercise regime coupled with a healthy diet and appropriate caloric intake will certainly limit the formation of visceral fat and will limit the infiltration of visceral fat into other parts of the body by pro-inflammatory immune cells.  In addition to limiting the amount of fat and its infiltration, exercise exerts additional benefits through the release of signals from our muscles and the body’s counter to these signals. 

All bodies try to remain in a state of balance.  Many of our biochemical pathways evolved as a response to certain conditions that knock the balance off.  In biology, many of the diseases that we experience are the result of this balance being offset in one direction versus the other.  In attempting to maintain a balance, if a tipping point is reached, the reaction can be such that there is no way to get back to the original set point; in essence the effects snowball into a condition that cannot be rescued without the addition of external help (in the form of medicine).  All medicines are designed to aid the body in reaching some set point equilibrium.  Think of a run-away train speeding down a mountain and medicine as the addition of brakes.  If the accumulation of disease signals can be stopped, and in some cases reversed by the application of a medicine, disease states will be either in remission or cured. 

When we exercise, our muscles begin to burn stored glycogen.  This results in a release of IL-6 myokine from the muscle cells themselves.  During high intensity exercise the concentration of IL-6 in the blood begins to increase and the concentration is dependent on the duration of the activity; longer and higher intensity activities will result in a larger increase of circulating IL-6.  Since this increase in IL-6 is not conducive to the body’s balanced state, it reacts by releasing compounds that counter act activities of IL-6.

IL-6 mostly acts as an alarm signal for the immune system, calling into action the big hitters.  It is normally released by cells under attack, and signals to the immune cells whose job it is to destroy pathogenic invaders.  IL-6 release is great for when a bacteria or virus is invading the body, but terrible if released unchecked during exercise.  If allowed to circulate for prolonged periods, the IL-6 released by our muscles would eventually destroy us, as the big hitters would start attacking anywhere that the signal was too high, essentially destroying us from within.

So how do we quench this release and how does it help us?  When IL-6 levels from exercise get too high in the blood, the body releases the anti-inflammatory cytokines IL-10 and IL1 receptor antagonist, as well as cortisol (a very potent anti-inflammatory compound).  The IL-10 and IL-1 receptor antagonist pathways act against the IL-6 pathways which leads to an anti-inflammatory response.  The caveat, however, is that the level of exertion must be high and prolonged in order to gain an anti-inflammatory benefit.  Thus why the relatively recent recommendation to get 1-2 hrs a day of high intensity exercise to stave off diseases caused by inflammation (such as heart disease).  The key is to reach a state where the anti-inflammatory compounds outnumber the pro-inflammatory compounds by tipping the body’s balance in the other direction.  If the anti-inflammatory compound ratio is higher than pro-inflammatory compounds, an individual will benefit from this.

So, what about people who exercise all the time, will they be super humans?  In some cases, prolonged high intensity exertion can lead to suppressed immune responses, and in turn, to the development of infections.  Remember, a body will always try to maintain a balance, and if the balance is tipped too far, as in this case from too much exercise, the negative aspects will be more infections, as the immune system is too inactive.

Therefore it is important for both sedentary and over active individuals to find their balance.  Too sedentary of a lifestyle will lead to a chronic, low-level inflammatory state and can lead to one or more of the diseases prevalent in our modern times.  Too active and it may lead to more infections.  So if you’re sedentary; go exercise! If you exercise too much; take some days off!

Since a disease state is usually the product of a balance that cannot be tipped back (without help from medicines) the key is to not let that balance get out of control in the first place.  Exercise is a simple and yet effective method to keep obesity and chronic low-level inflammation at bay, and is certainly worthwhile to anyone as potential medicine to fight many of the diseases of our modern times. 

Ebola and It's Possible Treatments

With the recent Ebola outbreak there have been many concerned and panicked people about the threat of this disease.  While terrible, and certainly life threatening for all those unfortunately infected, Ebola is difficult to catch in most circumstances.

The caveat being that one must avoid bodily fluids of the infected to protect oneself from becoming infected themselves.  So why the donning of patients in "space suits" when they are transferred to hospitals able to treat their disease?  With Ebola the gestation period of the virus is approximately 21 days, which means individuals can remain relatively normal all while an infection is brewing inside them.  Once the patient experiences symptoms and shows fever the virus has reached such a large level within the body that the individual becomes infectious (and shows signs of high fever).

The viral load within the body is very much like a dam.  If it rains just enough a dam can keep the water at bay; however if it were to rain constantly for 21 days non-stop, the water may begin to spill over.  When an individual is showing a fever the level of Ebola virus particles within that person has become high enough to begin to leech out of the person.  Thus, there will be Ebola virus in every bodily fluid within the infected person.  The "space suit" is there to protect the first responders from the infected individual and to protect the inanimate objects that could harbor these fluids and infect others.

Ebola is a disease whereby the viral load grows higher as the individual becomes sicker and Ebola virus level is highest when the patient dies.  Right now the virus can only be transferred through bodily fluids, which if there is any way to draw a silver lining from this crisis, it is that fact alone. 

Currently there are several small molecule and biologic drugs begin developed to help treat Ebola.  Zmapp is the name given to an experimental drug that is comprised of the combination of 3 chimeric monoclonal antibodies developed by Leaf Bio, an arm of the Mapp Biopharmaceutical company.  The ZMapp therapy consists of 3 antibodies developed through recombinant DNA technology and genetic engineering and consists of mouse antibodies grafted onto human IgG Fc regions (or fragment crystallization region). 

Zmapp is still considered experimental and hasn't been formally tested in efficacy and safety studies, but it was given to infected individuals during the recent Ebola outbreak.  The antibody cocktail is being produced in tobacco leaves, which is a plant that is often used in the production of transgenic protein.

Biologic drugs such as antibodies can not be synthesized like chemical drugs and must be produced in organisms through transcription and translation which occurs within the cell.  Other organisms that can produce transgenic proteins include bacteria (such as E. coli), Chinese hamster cells (CHO), human kidney cells (293), and insect cells, as well as others (such as tobacco and other plants).  One could probably use almost any cell type to express transgenic proteins given that the cell is properly motivated to do so (usually by applying selection pressures) and the correct expression cassette is utilized (ensuring proper gene expression under specific gene expression promoters).  Each expression system has its pros and cons. 

It is anyone's guess at the moment as to whether or not the Zmapp combination will work on a large scale, but given the sheer volume of current and possibly future Ebola infections it is worth pursuing. 

Introduction to All Things Science blog

I have always loved nature and the natural world.  So it was no surprise when I learned a love of biology early in middle school.  Biology became a fascinating thing to me at an early age and by the time I was at college I found myself in a molecular biology major at the University of New Hampshire. 

It was here that I had my first taste of a research project.  I had an excellent opportunity in Dr. Paul Tsang's lab from UNH's animal science department researching the localized expression of MMP-13 in cow corpus luteum, and had the opportunity to work with a great mentor: Bo Zhang, who helped and guided me along the precarious research path. 

After graduating with my degree I went on to the University of Connecticut to pursue a master's degree in biotechnology.  During this time I was exposed to many different types of subjects ranging from biochemistry to fermentation and biophysics.  I had several stints in different research labs doing work on quorum sensing in bacteria found in the leech gut and started a project studying the protein folding of Salmonella bacteriophages. 

I had an opportunity to continue with a PhD from UConn and decided to stay.  At first I was in a biophysics lab, but after several months I was not exactly sure that biophysics was the right path for me.  I was lucky enough to transfer to a newly established facility known as the Center for Regenerative biology with Theodore Rasmussen where I began studying epigenetics and stem cell's with a specific emphasis on the reasons why stem cells could do the amazing things that they do. From here I was able to do a summer internship with Pfizer's Stem Cell Center of Excellence. 

From Uconn I transitioned to Abbott labs (now Abbvie) in Worcester Mass, tasked with the development of therapeutic antibodies and dual-variable domain IgG's. 

As one can see I come from a varied background of scientific disciplines.  I have always followed my passions in science, and I wish to utilize this blog space to write about the developments that I feel are important and interesting.  I hope to use my experience to enrich your life with the knowledge of what's being done in the vast wide world of scientific research and why it will be important in your life one day.