Heparin II

Previously, I had written about contamination that occurred in a batch of Heparin and caused the death of a number of patients undergoing dialysis. Free Yevgeniy: Heparin To review, Heparin is a natural anticoagulant found in the intestine (lumen) of pigs. Heparin is a variably-sulfated proteoglycan that consists of repeating disaccharide units (pictured to the right). The compound inhibits binding to the clotting factor ATIII and stops the blood clotting process.

Last year there were pediatric deaths that created a commotion in the community and led to the FDA issuing an investigation. One of the academic specialists on Heparin, called to assist in to identify the contaminant, was professor Robert J. Linhardt, at Rensselaer Polytechnic University.

Dr. Linhardt, working with a larger group, helped isolate the contaminant as persulfonated chondroitin, a compound that mimics heparin activity in vitro but causes extreme damage, even death, in vivo.

Heparin is used in dialysis and for invasive hospital tools. Therefore a contaminant was a disaster for the health care community

Dr. Linhardt discussed the need for laboratory made Heparin so that we could better monitor the drug making process and avoid Heparin shortages.

Interesting points made during the talk:

• Pigs in china made four doses of Heparin vs. one dose in America. Turned out Chinese farms are dirtier and cause an increase in mast cell Heparin production as Heparin levels are elevated during a parasitic response
• Heparin was first used in 1926 (prior to FDA existence) and as a compound can not be patented
• While the current process for Heparin production is gruesome (filthy slaughterhouses --> large unregulated factories --> US markets), the contaminant was purposely added to the mix sometime during the process. This is important as the FDA can not allow any inserted contaminant to be present (non process derived), therefore purification is not an option
  
• France continued to use contaminated Heparin, since the alternative was to stop dialysis

Dr. Linhardt, and others, are now involved in commercializing an enzymatic process for Heparin synthesis. The main goal is not to reduce the cost of Heparin, but to create a viable option for the world market that could be better regulated to avoid future shortages.

This meeting was targeted to chemists and business people. Yet, it is an essential concept for all medical doctors to understand. It seems amazing that doctors have so much faith in the prescription pad to provide the right drug. Often generics are recommended because similar efficacy has been shown in trials and cost is decreased. Is quality lost? Cheap sneakers are often of poorer quality then more expensive ones. As a society, we expect our medication to be treated with higher regard then sneakers. However, the FDA is underfunded. Less then 10% of imported drugs are checked when shipments arrive. Until this Heparin crisis occurred, there were no full time FDA officials in China reviewing the manufacturing process. Can physicians rely on the drug market to provide what is prescribed? This continues to be a pivotal issue.

A joke at every end:

Why is Cinderella bad at baseball?
She runs away from the ball and has a pumpkin for a coach.

Who you calling Fat

This week it seems that fat has taken NY by storm.

The May 6th Edition of the Science NY Times had an assortment of fascinating articles that related to fat in some way.

1. Study Finds That Fat Cells Die and Are Replaced
2. Evidence a High-Fat Diet Works to Treat Epilepsy
3. Its Poor Reputation Aside, Our Fat Is Doing Us a Favor (older - Aug 7, 2007)
4. Redefining Disease, Genes and All (separate topic - somewhat related)
   

1. It was previously thought that fat cells developed until puberty, at which point the sex hormones (estrogen) helped direct where in the body the fat deposits went. After puberty, aside from changes due to extreme circumstance (like liposuction), the number of fat cells remained the same. The cells got bigger or smaller as you gained or lost weight. It was even shown that after liposuction, your body somehow regenerated the same # of fat cells as prior to surgery (these new cells were super skinny).

New research is showing that 10% of your fat cells die and are replaced every year. Oddly enough, nuclear bomb testing helped move this stuff forward. The radioactivity released by above ground bombs created a spike in Carbon 14 isotopes in the atmosphere. C14 has 8 protons and 6 electrons (2 more than usual). The natural abundance of C14 in the atmosphere is one in a trillion, therefore, spikes in the atmosphere made an imprint in all things created at that time. The half life of C14 is 5700 years (long enough to not make a difference).

This principal was applied to the whole body, and showed that certain fat cells were very young.

2. A high fat diet showed itself effective in a randomized trial to decrease epilepsy seizures in children. This diet has been evaluated for a long time now. 38 % of kids had 50 % less seizures as compared to only 6% of kids in the control group. On a personal note, my professor and I researched the effects of a high ketone diet on seizure patterns in Mongolian Gerbils.

Ketosis is the state of metabolism when the liver uses fats (instead of glucose) for energy and converts fat into fatty bodies and ketones. Fatty tissue becomes an important source of energy and diet has to maximize fatty intake to maintain ketosis.

To review our basics, a fatty acid is a carbon chain (with double/triple bonds - unsaturated, no double/triple bonds - saturated). Fat tissue tends to be composed of three fatty acids bonded to a carbon backbone. Adipose cells store a lot of fat.

3. This article discusses the important benefits of our fat cells. They protect our organs (visceral fat), provide the bulk under the skin (subcutaneous), store an important energy source, and are critical to supplement disruptions in diet. In addition, these fat cells release different hormones. Too much fat causes a release of inflammatory hormones to decrease obesity, they also release leptin (a compound involved in reproduction). Clearly fat is no joke (line might be stolen from NY Times).

4. Everything is interconnected. Everything. Obesity, Epilepsy, Bipolar disorder, Chronic Fatigue Syndrome. Our gene make up is so complex that undoubtedly relationships can be found and made in disease never before associated by their outward symptoms.

Muscular Distrophy and Heart Attacks share a gene in common. Two genes connect diabetes and prostate cancer.

Nosology - the field of disease classification - is about to get its head knocked. For example, Jonathan Kerr and company [J Infect Dis. 2008 Apr 15;197(8):1171-1184] have published a study of a genomic signature of 55 patients with Chronic Fatigue Syndrome. 88 genes are up regulated. 6 of them have previously been targeted by drugs.

Looking at everything floods the blackboard with an assortment of random thoughts. Once a pattern can be elucidated, though, the most powerful answers can be found.

Ideas:

• Studies show that African Americans and Caucasian populations lose different types of adipose tissue during diet and tend to have different adipose tissue for the same body mass index . These two groups also have different insulin patterns and different diabetic profiles. Fat cells are created every year - can we direct them to different locations? Will they excrete different hormones more conductive to a proper glucose response? What effect will a high fat diet (ketosis) have on the diabetic population (I have a feeling it will be different for African American and Caucasian communities).
  
• Personal story, patient with Chronic Fatigue just started a south beach diet (avoid bad fats and sugars), feels great. How does all this fit in? Separately, if Chronic Fatigue Syndrome is characterized by some inflammation, might fat cells be involved?
  

I need a blackboard and more fat.

A joke at every end:

What do you call a fish with no eyes?
Fsh!

- better said then read [no i(s)]