Thursday, October 29, 2009

Was it really around that long ago?

I've read countless articles on the receptor alphaIIbBeta3 and am really surprised how early on it was discovered. Its really fascinating to find out how advanced they were in science 100 years ago. I tend to forget that when I see their wardrobe and vernacular. I tend to think that anything microscopic must be a recent finding, within the last 20 years. But that is wrong. And even if it is wrong, it is still hard to grasp. This report has opened my eyes a little more to the abilities of scientists +1oo years ago.

Wednesday, October 28, 2009

Blood Clotting-A Dual Process

In the past week I have been busy reading more sources and trying to piece together exactly what goes on in the process from when you get an injury to when your blood forms a clot. I made a mistake when I did the initial research on this topic; I didn't take into account all the processes that create a clot.

Initially, I was under the impression that there was a chemical response that activated the platelets to form a platelet clot. I thought this platelet clot was a blood clot and fibrinogen was the activator and the molecule that formed the web like structure of the clot holding the platelets together. But that is only half the story.

On the other side you have the extrinsic pathway. This is what makes the fibrinogen into the insoluble fibers that form the clot. The extrinsic pathway is a series of activations where the produce of one reaction is the catalyst for the next activation. The steps in this activation pathway are knows as factors. The final factor is thrombin. Thrombin has a dual purpose in blood clotting. First, it is a negative feedback loop that causes the intrinsic pathway to repeat itself. It also is the activator for fibrinogen to form in fibrin monomers which in turn are activated to form into insoluble fibrin polymers, which trap blood cells into forming the red clot.

Both the red clot and the white clot combine to form a blood clot. Each process does half of the clotting.

My original question of : What would happen if you did something to the platelet receptor alphaIIbBeta3 still stands. You cant form a blood clot without both parts of the clotting process in check. The platelet white clot is the first to attach to the vascular injury and without it, the red clot cant do anything.

I can still focus on the platelet receptors, but it was important to understand the whole clotting process before I start. One does not exist without the other.

Monday, October 19, 2009

Blood Clots: Finding Sources and The Basic Overview

I never realized the plethora of information available out there on the internet on any topic. When I typed in "blood clots" into Google scholar, so much came up, I had to start reading the overviews just to figure out the specific topic I wanted to focus on. Reading all the papers was quite a challenge because the jargon used is so topic-specific that you have to look up almost all the words in the first few papers just to get a slight idea of what its talking about. It's not English, its scientific English, 500% harder to decipher than Shakespearean English!

I finally settled on platelet receptors and their role in blood clot formation. (I hope this follows through because the thought of changing my topic now is daunting)

Sources:
Integrins: Dynamic Scaffolds for Adhesion and Signaling In Platelets

The Contribution of the Three Hypothesized Integrin-Binding Sited In Fibrinogen to Platelet-Mediated Clot Retraction

GPIIb-IIIa: The Responsive Integrin


Structural basis For Allostery In Integrins And Binding To Fibrinogen-Mimetic Therapeutics

Platelet Physiology and Thrombosis

Platelet Receptors and Signaling In the dynamics of Thrombus Formation

Information:
After reading these sources, I have figured out the basic process of blood clotting through alphaIIbbeta3 receptors. A receptor is activated by an activator (ligand) and the receptor's morphology changes from being bent (inactive) to straight up (active). In its active form, a fibrinogen molecule can bind to the receptors on the platelets. Throbin, a protein in the blood that helps with thrombus formation, causes the fibrinogen to form insoluble fibrin fibers. Theses fibers are the web-like structure of the clot and hold the platelets, cells and other clotting factors in place so the clot can form.

I'm still researching how the integrin knows to activate the platelet. So far, I understand that when there is vascular injury, there is a chemical response, which triggers the integrins. What that chemical response and how that is triggered, I don't know yet.

Lets hope I can figure out the whole process!!

Wednesday, October 14, 2009

Blood Clots-A Research Question

When given this assignment last week, my mind immediately jumped to blood clots. This past summer I was doing some research in a vascular and hematology lab, and one of the projects was looking at platelet receptors to determine if there was a possibility of stopping blood clots . Since I left the lab, that idea has consistently been on my mind. I've wanted to do more research about what is available now to stop blood clots and what types of mutations are available, but have been to lazy and busy to do it. Now, I can.

Initial Research: Blood cells (platelets) are required to repair a damaged blood vessel. They adhere to the site of vascular injury and connect to each other, forming a clot. While this action of platelet clotting is important for maintenance of our bodies, if a clot forms in the wrong location at the wrong time (i.e. in a heart artery) a heart attack or a stroke could occur. The idea is to stop blood clots from being created.

What is a blood clot? "Blood clotting, or coagulation, is an important process that prevents excessive bleeding when a blood vessel is injured." (http://www.bloodthevitalconnection.org/for-patients/blood-clots/Default.aspx.aspx) On a general level, the blood cells come together and attach to one another, creating a thrombus. At a closer level, it becomes evident that receptors on the platelet membrane become activated in the presence of fibrinogen and bind to the soluble glycoprotien, creating a web-like structure. This thrombus becomes so close together that it forms a wall like structure, not allowing anything to pass in or out of the blood vessel. It keeps the temperature, concentrations and materials of the blood vessel in the body. A scab can form on the outer layer of skin from the dried blood of the injury. This is another layer of protection.

However you cant just stop blood clots from being created because they are also beneficial. So whatever action you do to stop them form forming must have an opposite counter action to allow the platelets to aggregate. This is where the tricky part comes in.

While doing some reading, I came across the idea of blood thinners as a cure. There are many varieties out there (a small list-http://stroke.about.com/od/caregiverresources/a/blood_thinners.htm) and they generally work along the idea that thinning your blood keeps the platelets further from each other so that they don't clot. Before you go into major surgery, you stop taking the blood thinner so that you can clot normally and heal your injury. There are side effects to blood thinners, such as kidney issues, stomach ulcers and breathing issues, to make a few. So blood thinners are not the answer for everyone.

What I would now like to do is investigate another way of stopping platelet aggregation. Is there a machine? Is there another internal method?

Monday, October 5, 2009

Abstract Thinking 1: The Search For a Structure

As engineers, we must learn to think in the abstract. Dr. Bogen told us in class that “engineers control the physical world through abstractions.” This is a nice concept, but somewhat hard to implement into our daily lives. I’m not the best abstract thinker. In fact, for any given abstract term, I try to turn it into a physical manifestation. For instance, with feelings, I associate a reaction or an example of the feeling for what it really is. I wouldn’t know how to describe the actual feeling without using these examples. But as an engineer, I guess I will just have to learn how.
As an assignment to learn how to figure out this abstract concept, we were told to find a structure on campus and describe it in three lengths. What? What does that mean? That’s what I’ve spent the last week trying to decipher.
I wanted my structure to be different than everyone else’s. It’s sort of boring to have the same thing as someone else. So I first tried to think out of the box. There are two aspects to this type of thinking. It could either be totally obscure that no one else would think of it, or it has to be totally normal, right in front of your eyes that everyone else would just glance right by. I attempted the first type because that is ultimately the cooler and more interesting type. But I was unsuccessful with that. I could think of strange structures, but measuring it in three lengths was a challenge. So I switched to the second type of out of the box thinking. I sat down on a bench in the quad outside my dorm and looked at everything in front of me.
I first noticed a tree. That’s not a structure. Then I saw the wall of the building itself. As easy as a building may be, I didn’t think it would be a challenge to describe in three lengths, hence no real expansion of abstract thinking. So I continued to look. After focusing on a few other structures and throwing them out for various reasons, I focused on a bike rack. Its structure is so simple, yet so hard to describe and measure. So I have finally found my structure: I will be using a bike rack.
Now on to measurements. Are the three lengths supposed to be in cm, area and volume? Or is it a structural measurement? Or a functional measurement? A combination of all three? So confusing.
Wish me luck, because I’m a little lost about how to go about my measurements and descriptions.