Understanding Graves' Disease

What is Graves' Disease

Irritated, enlarged eyes that look like they're about to pop out are the most noticeable symptom of Graves' disease, an immune system disorder that leads to the thyroid gland producing too much thyroid hormones.  In this disease the body will produce antibodies which over-stimulate the thyroid gland, and usually also attack and inflame the tissue that lies behind the eyes and skin on the lower legs.

Diagnosis

• In order to diagnose a patient the doctor will need a blood sample in order to test the levels of TSH (Thyroid stimulating hormone), T3 (triiodothyronine) and T4 (thyroxine).  Sometimes the test will also measure TSI (thyroid-stimulating immunoglobulin.
• Another method to diagnose for Graves disease is Radioactive Iodine uptake test. Once Iodine is placed in the blood stream the thyroid gland will absorb it, and by measuring the rate of absorption the doctor will see if the thyroid is being over-stimulated.
• A CT scan and MRI is used to check eye problems that are associated with Graves (inflammation of the tissue behind the eyes, redness, swelling which appears to make them pop out).
  

Mechanism of action

• T3 and T4 are produced by the thyroid gland (located right under your vocal chords) and they are in charge of controlling the metabolism in the body, particularly the rate at which molecules are created or broken down. TSH on the other hand is released by the pituitary gland (located under your hypothalamus) and it is in charge of controlling how much T3 and T4 the thyroid makes. If the level of any of these three is higher than normal it is indicative of a thyroid problem, and particular for Graves disease is present if the T4 level is higher than average.
• High level of T4 increases the rate of metabolism of the body, which affects weight,  physical appearance, increased sweating, difficulty concentrating, anxiety, heart palpitations or arrhythmias, fatigue, high sensitivity to heat,  menstrual irregularities etc. But as mentioned previously, eyes that seem to be bulging out is one of the outcomes that can be noticed quickly, along with an enlargement of the thyroid gland noticeable in the neck region.

Treatment

• To treat Graves disease the doctor will prescribe anti-thyroid medications which decrease the production of T3 and T4.
• Radioiodine therapy can also be helpful for Graves. A patient is prescribed an iodine solution to be taken orally, which allows iodine to collect in the thyroid and over time this will kill the overactive cells. After this therapy the patients will likely need hormone replacement therapy.
• Beta-blockers (short for Beta-adrenergic blocking agents) are also prescribed in order to reduce the heart rate, anxiety and sweating. This group of drugs blocks the effect of epinephrine (adrenaline) which makes the heart beat more slowly. Examples of Beta-blockers that are commonly prescribed by doctors are: Atenolol, Bisoprolol, Metoproplol, Propanolol etc.
• Lastly, an alternative to medications is surgery to remove the thyroid, which is followed by hormone replacement therapy.
• There are also ways to treat the symptoms that are not thyroid related . For eye irritation the doctor will prescribe Prednisone, a steroid drug. Some patients have to use tape to keep their eye lids closed at night to prevent them from drying. Leg skin inflammation is handled with leg wrappings with ointments.
  

Until next time,

A.M.D

Bart syndrome

I just came across a disease called Bart syndrome which may very well be the strangest disorder I have heard of to this day. It is a genetic condition that makes the fetus not grow skin in certain areas of the body, causes blistering and scarring where skin is actually present and nail abnormalities. Usually the baby's feet below the ankle or hands will have a thin membrane over the flesh but will be missing skin layers. Blisters tend to appear around and inside the mouth and on the belly, shoulders or even head. It is an autosomal dominant disorder, which means that both parents have to be carriers of the mutant version of the gene in order to transmit it to the baby. The difference is in the gene that makes Collagen Type VII on exon 73 of chromosome 3, where a Guanine nucleotide becomes an Adenine nucleotide. This changes the normal Glycine amino acid into an Arginine which alters the structure of the anchoring fibrils that hold tissue together. The feet and hands are the parts of the body where this anchoring is most important so they tend to display the condition.

So when a baby is born with the Bart syndrome he or she will need to wear a sterile dressing around the problematic area with a saline and antibiotic ointment that needs to be changed daily to prevent infections, very gently otherwise bleeding will occur. This is currently the only way to manage the disease. In some cases even with the dressing the digits tend to fuse together and the hands and feet lose their structure.  Luckily Bart syndrome occurs in only 1 in a million babies, but still, a very strange condition.

Until next time,
A.M.D

Project description

I started my internship a couple of days ago and I am very excited for my project.

Initially I was told I would be working on antibiotic delivery to wounds through an infinity-based system which I wrote about earlier but when I received my project description I realized I was working on a different area. Same concepts, but different application. My project will develop a delivery system for Paclitaxel utilizing Cyclodextrins through a bare metal stent, which will be functional under 600ml/min flow in an AV fistula.

When an AV fistula fails it is because of neointimal hyperplasia due to high stresses which leads to stenosis. The solution to this is angioplasty which is done through a drug-eluting stent, in this case Paclitaxel, an antiproliferation agent sold under the brand name Taxol, a common chemotherapeutic drug.

In plain language:

In patients with a high risk of kidney failure hemodialysis is the solution (pumping blood out of the body through an apparatus that removes toxin - a.k.a fake kidney). The best mechanism for dialysis is through an arteriovenous fistula. A fistula involves a surgical procedure of tying a vein directly to an artery, and skipping the arterioles, capillaries and venules that are in between. Blood in the artery flows with a high pressure whereas in the vein it has a low pressure. This difference creates unbearable shear stresses in the vein portion and the hope is the fistula will mature to sustain these stresses. In a lot of cases however the stress  results in a series of events that ultimately cause more cell reproduction (neointimal hperplasia) in the region which leads to the narrowing of the vessel (stenosis) so it can no longer be used for hemodialisys.

The solution to stop the narrowing is to insert a metal stent (a tube to keep the vessel open). This however does not fix the cause of the problem (the increase in cell production) so it is not entirely efficient. But if the stent is coated with a antiproliferating agent (a drug to stop cell growth) then its release would stop cell growth and prevent the narrowing of the vessel.

Paclitaxol is one of these antiproliferating agents (a.k.a chemotherapeutic drug). But the problem with it is that it is very insoluble in aquaeous solutions. In order to overcome this issue one method is to use Cyclodextrins (CDs) - sugar molecules that are naturally a product of bacteria digesting cellulose.  Fun fact - Febreeze uses them in their air-refreshing products. CDs have a teroid geometry with a very hydrophobic internal part which can host hydrophobic drugs like Paclitaxel and a very hydrophillic outside which helps dissolve the drug in aquaeous solutions.

So essentially what I'll be working on is getting the drug inside CDs in the right concentration for an AV fistula and getting it to dissolve for as long as possible in a linear fashion.  The problem is Paclitaxel has always been used systemically not locally, so I'll have to figure out things from scratch instead of reading the literature.

Happy bioegineering,

A.M.D

REU at Case Western

A few weeks ago I was notified of my acceptance to the BME REU program this summer at Case Western University in Cleveland, Ohio. For those of you who don't know, REU stands for Research Experience for Undergraduates. It is a form of a paid summer internship at a university funded by the National Science Foundation, designed to introduce students to the world of research by pairing them with a mentor professor. This will be my first lab experience to combine both engineering principles and knowledge in the biomedical field, so I am excited to see where I stand.

Today I just received my project topic for the summer. The exact title hasn't been chosen yet, but I know I will be working with Dr. R. on designing antibiotic drug delivery systems for wounds based on affinity. At this point I know very little about how affinity principles are used in drug delivery so I will have to do plenty of research before I head to Ohio. I do however have a paper  to study from, from old research done in the same lab where I'll be working. I briefly skimmed through it and it seems like it deals with non-covalent molecular interactions such as hydrogen bonds, Van der Waals, hydrophobic interactions and ionic bonds between the solute and the delivery system.  

I will be writing more about it when I have time to fully read the paper and do further research. For now, I am looking forward to this summer, it should be interesting on many different levels.

Happy bioengineering,
A.M.D