Chocolate May be good for you.

The most recent group of papers sent to us included two seperate papers making reference to chocolate and its anti-inflammatory effects. The first was "Snacking in the Line of Duty." Here was a very quick reference to flavanols which "relax blood vessels, improve blood flow, decrease blood clotting and redue inflammation." The second article was "Chocolate 'has health benefits'". After reading these articles idecided to look at this more closely. When I typed in "flavanol" in the Yahoo search engine 4 of the first 5 entries were from the Hershey Company. Looking at these entries they were using their website to explain the benefits of flavanol. Surprisingly they also mentioned flavanols could be found in berries, teas and red wines as well. Without disputing the positive effects of flavanol I think we can still say chocolate will not be changing it's status to "health food." As the Snacking in the Line of Duty article shows, having some benefits, such as flavanols, does not necessarily outweigh the downside, such as fat and sugar. The second article makes mention of diabetics eating chocolate. However, if you look at the ingredients in Hershey's Special Dark chocolate bar the first ingredient listed is still sugar. If the individual has Type 2 diabetes, the flavanols might help with the metabolizing of sugar but if the individual is a Type 1 diabetic, the pancreas is not producing insulin and the individual will need to inject higher doses of insulin to compensate for the higher intake of sugar.
Unfortunately for the many chocolate lovers in the world it looks like more evidence will be needed to say it actually has "benefits".

Comparison of the Intestinal Toxicity of Celecoxib, a Selective COX-2 Inhibitor, and Indomethacin in the Experimental Rat

Gastrointestinal toxicity of NSAIDS appears to be due to a “topical” effect and inhibiting of COX-1; where as, selective COX-2 inhibitors show great GI tolerability. The “topical” component in the pathogenic mechanism for damage is thought to involve the uncoupling of mitochondrial oxidative phosphorylation with increasing intestinal permeability. (The "topical" effect may be due to the detergent-like action of NSAIDs, with the combination of their lipid soluble component and acidity.)The increase in permeability leads to mucosal inflammation. This inhibition may cause inflammation to turn into ulcers. COX-2 is thought to suppress PG synthesis in the areas of inflammation, while also controlling constitutive PG synthesis in the GI tract. This idea was tested using Celecoxib, a selective COX-2 inhibitor, and Indomethacin, which is a non-selective acidic COX inhibitor.

Celecoxib did not have a “topical” effect in their experiment assessing mitochondrial functioning, nor did it lead to changes that may be characteristic of uncouplers of oxidative phosphorylation. Indomethacin did both, while causing intestinal ulcers! Celecoxib did not show any significant damage to the small intestines though, and showed a lack of reduction in intestinal PGE; where as, Indomethacin reduced PGE levels 90%. Indomethacin clearly has damaging effects on the intestines, but Celecoxib does not. The combination of its selectivity and absence of a “topical” effect is thought to be the reason. I found this article interesting, as it went more in depth than I did here, in explaining the possible effects of these NSAIDs because many people around the world are on anti-inflammatory medications. Granted these experiments were done in rats, and one drug was shown to not be harmful, many people have complications with anti-inflammatory medications. They can be quite helpful but are they always worth the risk?!

Oh yeah....That gerbil is awesome!

NSAIDs & Asthma

I thought it was very interesting that Kerry brought up the adverse effects of NSAIDs on asthmatic people, so I did some research to see if a mechanism had been found.

I came across an article from the June 2007 edition of the journal Allergy (vol. 62). Wang, X.S. et al were able to culture mast cells (cells that are like basophil granulocytes and are involved in allergies) from peripheral blood progenitors into mature cells that resembled human lung mast cells. They cultured these cells from 3 groups of patients: normal/healthy patients, patients with aspirin tolerant asthma (ATA) and patients with aspirin exacerbated respiratory disease (AERD)--these are the ones at risk for increased bronchospasms due to NSAIDs.

Basically, the research group found that AERD patient mast cells are different from mast cells of the other 2 groups. AERD mast cells, when activated, can produce much more cysteinyl-leucotrienes (cys-LTs), which are chemical messengers involved in inflammation. cys-LTs help regulate the state of blood vessels and airways.

In addition, PGE2 decreases this overproduction of cys-LTs. So when AERD patients take NSAIDs and inhibit COX as well as PGE2 synthesis, this enables the increase in cys-LTs. More specifically, cys-LTs cause asthma attacks by allowing for bronchoconstriction, increased mucus secretion in the airway and infiltration of leukocytes in the airway. In fact, leucotriene receptor antagonists are used to treat asthma.

So...there you have it. =)

Most Recent Celebrex Side Effect

Celecoxib, marketed as Celebrex, is an NSAID commonly used in the treatment of rheumatoid arthritis. Celebrex hit the market just under 10 years ago as an “alternative” NSAID with the same pain relief but fewer adverse gastrointestinal effects than “conventional” NSAIDS like ibuprophen and naproxen. As an “alternative” NSAID, Celebrex is a highly selective COX 2 inhibitor, whereas the “conventional” NSAIDs inhibit both COX 1 and COX 2. Because Celebrex is a relatively new NSAID, the side effects, risks, and suggested dosages seem to be changing rather frequently. The most recent and detrimental risk that has been identified for Celebrex is heart attack and stroke. As recent as 2007, Celebrex was deemed a drug that should be used as a last result anti-inflammatory medication for those who are at risk of heart attack or related cardiovascular disease. It seems like every year that changes to the Celebrex label have to be made to add more side effects and risk factors. I don’t know how the typical FDA approval and initial marketing of new drugs usually plays out, but it seems like there have been a lot of detrimental effects caused by Celebrex, and the Pfizer company who markets the drug is trying to focus solely on the fact that it has decreased gastrointestinal risks. So until their large scale clinical trials are complete in 2010, my suggestion would be to steer clear of Celebrex and find another NSAID that has been around long enough to have all of its risks and benefits ironed out.

The Bad and The Ugly of NSAIDs

In this week’s reading, “Comparison of the Intestinal Toxicity of Celecoxib, a Selective COX-2 Inhibitor, and Indomethacin in the Experimental Rat,” it mentions that non-steroid anti-inflammatories or NSAIDs are implicated in gastrointestinal and small bowel side effects. To put this into context, I looked up what exactly these side effects include, and found that NSAIDs can cause ulcers, diarrhea or constipation, loss of appetite, liver failure, kidney failure, and hemorrhaging. People with asthma can experience more exacerbated side effects, which can even lead to death because NSAIDs can induce bronchospasms. However, like with most things in science, it is not well understood why NSAIDs cause a more severe effects in asthmatic people. Maybe someone in our class has a guess as to why?

Comparison of Toxicity of Celecoxib vs. Indomethacin

There have been several factors that can lead to the damage of the gastrointestinal tract from NSAID's. There are two main mechanisms for the damage, one involves a the uncoupling of mitochondrial oxidative phosphorylation while the other is the inhibition of COX-1. For the peer review articles this week, it was suggested that the inhibition of COX-2 would suppress the prostaglandin synthesis at the sites of inflammation. To research this, the study used selective COX-2 inhibitors such as Celecoxib and Refecoxib while using Indomethiacin as the positive control in experimental rats.
The rats were treated with the drugs and such factors that were observed were in vitro which measured the liver mitochondria, in vivo which was measured through electron microscopy, intestinal permeability which was measured in urine excretion, the granulocyte marker protein which was taken by faecal samples, Intestinal prostaglandin determination which was taken by freezing the small bowel of the rat in liquid nitrogen and the prostaglandin was extracted from the sample and measured, and finally macroscopic damage which was done by performing a laparotomy on the rats and recording the amount of ulcers that were present upon dissection.
The results after gathering and assessing all the data was that the selective COX-2 inhibitor (Celecoxib) had no significant damage on the small intestine mucosa when compared to Indomethacin. This was probably due to the significantly less reduction that Celecoxib had on PGE levels when compared to Indomethacin which had a 90% reduction in PGE levels. Also to note is that Celecoxib did not lead to physiologic changes which is common with uncouplers of oxidative phosphorylation while Indomethacin showed all parameters of pathophysiologic changes and also caused intestinal ulcers which were present during the laparotomy. To summarize, when compared to Indomethacin, the Celecoxib showed no association with intestinal toxicity in the given study models.

One for the Ages???

After reading this lay article I found several points that left a bad taste in my mouth. One of the key problems I found was the author's lack of significant proof. When he finally mentioned some numbers to back up the suggestions they were scarce and prove nothing. Out of the original 76 rhesus monkeys only 50 are still alive. There is no mention here about how many were from the experimental group and how many are from the control group. The difference in cancer of 5 to 3 (control vs. esperimental groups respectively) is not a significant difference. In addition the causes of cancer are still not fully understood so this is quite possibly due to the randomness of the disease.
The author also wrote about the "lower insulin levels". If we think back to PSIO 202 we can recall insulin is released by the pancreas in response to sugar levels. Now, if you are taking in less calories you are most likely taking in less sugar.
Another point that is not mentioned here is the quality of the diet. If someone were to reduce their caloric intake it would be necessary for them to maximize the amount of nutrients in their diet. To put it another way if you are going to eat less than a normal diet, that limited amount must be of a higher quality. With that in mind how much of the longevity observed is due to less calories and how much is due to a better quality diet.
Sorry to sound like a skeptic here but there just seemed to be too many gaps in the information to convince me.

Possible Deaths due to Heparin

In class last week it was discussed about the safety of warfarin compared to heparin. I've recently looked up a article from the FDA stating that possible deaths related to heparin use could be higher than expected. I posted the link below and there is another link within the article that shows figures from Jan. '07 to March '08. My personal view of the article is probably the same as any other lay article, I cant say much on the accuracy and credibility, but could still be considered an interesting read.


http://www.medscape.com/viewarticle/572751