Adiponectin: Friend or Foe?

So a couple weeks ago we were discussing Inflammatory Bowel Disease (IBD)and the possible role adiponectin played in its pathogenesis. As a just a quick recap, adiponectin is an adipocyte specific secretory protein that plays many different roles in the innate humoral immune system; in relation to IBD, and more specifically Crohn's Disease, it was proposed in one of the papers that it also has anti-inflammatory effects. In the study conducted, it was concluded that the adiponectin secreted from adipocytes in hypertrophied mesenteric adipose tissue could serve as a barrier, preventing the inflammation from spreading into the intra-abdominal space. In this case, adiponectin plays a positive role, limiting the damage done by the inflammation.

As is the case with many different inflammatory and anti-inflammatory proteins, adiponectin's roles are not limited of course to its actions in Crohn's Disease. What I wanted to know, however, was if adiponectin also has possible positive effects, if any, when it came to arthritis. When i did a little research, I was surprised to find out that in the case of Rheumatoid Arthritis (RA), adiponectin may actually play a significant role in the pathogenesis of RA. What was demonstrated in the study I found was that adiponectin stimulated the production of vascular endothelial growth factor (VEGF) and MMPS, which could lead to an increase in the joint inflammation and destruction. This study did state, however, that there must be more research conducted to prove these findings.

Toads and Humans

Hello everyone! When we first read the article about cane toads and arthritis in class I found it somewhat amusing. However, the more I thought about it, the more saddening I realized it really was. The toads in Australia are growing and evolving past their natural size. A huge part of this is due to that fact they have no naturals predators in Australia. Humans relocated them, and now they are becoming much larger in detriment to their own health.

After thinking about the toads for a while I began to think about diseases such as acromegaly, gigantism and marfans syndrome, which are all characterized by excessive growth and large size. From watching medical documentaries and odd history channel shows like “world’s tallest man”, I’ve heard that most people of increased stature and size, say eight feet, endure horrible arthritis. I remembered their joints being enlarged and put under horrendous stress due to the force applied to them. When I went online to search for more information, the thought of obesity popped into my mind and I realized I didn’t get much thought to it when it was mentioned in class. I thought about the billions of Americans who are obese, who weren’t born with a rare chronic metabolic disorder such as acromegaly, and who are by choice putting their body under massive stress. When I searched this topic I found countless websites stating an increased risk in osteoarthritis. According to the John Hopkins Arthritis Center, “being only 10 pounds overweight increases the force on the knee by 30-60 pounds with each step”. Imagine then what an extra 50 or 100 would do. While most of the research is still debating to what extent it increases your risk, “over five times the risk” and so on, it is clear that it is a large contributor to societal increase in osteoarthritis. In addition to increased stress and force there are also several “excess obesity hormones” being investigated for their roles in arthritis, such as leptin. Anyways, after feeling sorry for the toads, I realized it was even more sad that something so similar, yet something we as humans can control, is happening in our society.

What the heck are pannocytes?!?

While we were discussing the paper mentioning pannocytes in class, I realized I had no clue what those cells were. Here are some facts about these cell types based on an article I skimmed:

• These cells are found at the sites of RA cartilage injury but not in osteoarthritis cartilage.
• Morphologically, they are rhomboid in shape while fibroblasts are bipolar and chondrocytes are spherical.
• Chondrocytes are short lived (6-8 divisions) but pannocytes have a much longer life span (25 divisions)
• Both pannocytes and chondrocytes can produce collagenase and stromelysin, both of which are proteases that destroy the extracellular matrix. The kicker: pannocytes live much longer than chondrocytes...

For further info see: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857892/pdf/amjpathol00027-0336.pdf

-Vinoo

Spinal Drug Administration

http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030338

Here is a link to the lay article number two covered previously in class. We discussed the possible benefits, if any, and the logic behind administering drug through the spine to modulate peripheral response. The article in itself didn't do much to describe the full process or techniques for which this type of experiment would be conducted, that is why I have attached a link for those that are interested.

In reading the full research experiment and carefully critiquing the process and thought behind doing such a test, a few positive benefits arise as well some side affects, which could possibly be detrimental. By administering the doses through the spine, a smaller dosage of treatment would be required to reach the desired effect, thus resulting in a saving of money and possible better distribution and targeting of the drug. But also we must understand that all these tests were conducted on rats and not human samples. Though there are many parallels between systems, there is no guarantee that the results will be the same. The goal which was desired was to see whether CNS is essential to achieve a response even when administered as a systemic treatment. Which in turn means that there would be a change in the way that drugs are manufactured, in hoping to get to the CNS quicker and easier, to achieve lower doses while improving efficacy.

Glucosamine, any effect or just a placebo?

Everybody has heard of glucosamine as being the one-stop treatment for restoring cartilage and thus eliminating a lot of the pain associated with arthritis. The premise behind the supplement is that glucosamine is a precursor for glycosaminoglycans, which are a building-block in cartilaginous tissue. By providing glycosaminoglycans, it is assumed that cartilage can be rebuilt. However, no substantial evidence exists confirming its effectiveness.

In fact, studies performed at the University of Laval in Quebec indicate that over-consumption of glucosamine frequently happens, due to the fact that as no positive effects are felt, people are more inclined to take more until satisfied. Over consumption of glucosamine has been tied to developing type 2 diabetes by killing pancreatic cells. Furthermore, those that have allergies to shellfish have reacted badly to the supplement, due to glucosamine being an active factor in shellfish exoskeletons.

Of all the scientific studies performed on this supplement, many have been a little dubious in their findings. Of these studies, the primary sponsors were health supplement providers and low numbers of patients, with little or no controls, provided results that give the appearance that glucosamine does in fact treat arthritis. However by eliminating the studies that had loose guidelines, it was observed that glucosamine has no noticeable affects over a placebo.

Arthritis is a growing problem that plagues many young and old alike. But is it worth taking a supplement that has minimal scientifically-proven results, and even may be more detrimental to ones health than originally thought?

Gout: A historic disease of the "wealthy" transitions into the 21st century

Over the last few years I have noticed a substantial amount of men affected by gout; however it seems much less prevalent in women. I asked a few people and I really didn’t get a solid answer, so I did a little digging and found a really cool article published in the New England Journal of medicine in 2004 “Uric Acid and Diet — Insights into the Epidemic of Cardiovascular Disease"

Summary points:

· Gout has been described throughout history, as early as 4 B..C; originally thought to be a disease of the wealthy, affecting middle-aged men of wealthy upper class. It was associated with those that could afford the opportunity of overindulgence.

· “Humans are the only mammals which gout develops spontaneously.” This is thought to be because of mutations that occurred in the promoter region of the uricase gene. Uricase is the enzyme that converts uric acid to allatoin.

· This point addresses the men vs women factor: Estrogen stimulates urinary urate excretion, thus premenopausal women have lower serum uric acid levels.

· In the 1700’s it was proposed that a diet low in protein and high in dairy could decrease gout’s prevalence. Study in 2004 found gout was associated with diets high in meats and seafood and low in low-fat dairy. In fact they found an increase in risk of 21% per addition portion of meat per day. Populations with diets low in animal products and high in vegetables have a relatively low uric acid levels.

· Gout development is now following our current obesity trends. Higher populations of obesity have higher incidences of gout; even when these populations had lower rates throughout history, when obesity rates were lower (i.e. Maori of New Zealand).

· Recommend diets rich in fruits, vegetables and low-fat dairy foods (i.e. DASH diet)

So it seems that gout is following the obesity footsteps across the world, leaving behind the “wealthy” stereotype of the past and now affecting those at high risk of many other co-morbidities. Looks like it all comes back to a healthy diet…..

Johnson, R and Rideout B. Uric Acid and Diet--Insights into the epidemic of cardiovascular disease. N Engl J Med 2004; 350:1071-1073

Gouty Arthritis

Hey everyone! Most of what we're focusing on in this class as far as arthritis goes is OA and RA, but I had some questions about gout because I hear about it so often.
I found this lay article published today (http://www.medicinenet.com/gout/article.htm) that had some good info in it. Here are some of the main points from the article:
-Gout results from excess uric acid in the blood that can condense and form uric acid crystals that get caught in the joints, causing pain and inflammation (arthritis).
-The actual correlation between hyperuricemia and gout isn't clear because some people with hyperuricemia do not develop gout.
-Gout is more common in men than women; other risk factors are: obesity, diuretic intake, high alcohol intake, kidney problems, hypertension, and eating a lot of meat because meat contains more purines, which increases uric acid levels.
-Acute gouty arthritis is most common in the big toe (weird!).
-Treatment for gout includes anti-inflammatory use (but not aspirin, as this increases uric acid levels), weight loss, decreased alcohol consumption, decreased organ meat intake, and increased dairy consumption.

Read more for more info. Some of you may already know all this, but I thought it was pretty interesting, and it is clearly very preventable.