Iron Accumulation in the Brain may lead to AD and PD.

Multiple recent studies have been published pertaining to iron accumulation in the brain and a correlating incidence of neurological disorders. Many studies have been published particularly surrounding Alzheimer's and Parkinson's disease. Authored by Zecca et al., Iron, Brain Ageing and Neurodegenerative Disorders, focuses on this correlation.

Iron accumulation has been linked to multiple neurodegenerative diseases; it is believed that the build up iron causes an increased amount of oxidative stress which can be responsible for neurodegeneration. The iron accumulation in the brain increases preferentially in areas that are impacted by AD and PD. Some evidence seems to indicate that the accumulation of iron in the microglia induces the inflammatory response common amongst many neurodegenerative diseases.

In the case of Parkinson's Disease, increased iron accumulation is seen in the substantia nigra in extreme cases. Iron (III) specifically can be seen accumulated in the oligodendrocytes, astrocytes, microglia and portions of the substantia nigra of PD patients. In Alzheimer's Disease, iron seems to promote both deposition of amyloid-B and oxidative stress which are associated with plaque deposition.

This provides a unique link between metabolic needs, nutritional regulation and neurodegenerative diseases.

Reference for the article: http://www.nature.com/nrn/journal/v5/n11/pdf/nrn1537.pdf

New Clues to How Fish Oils Help Arthritis Patients

I've always heard that fish oils are good at reducing inflammation. I thought this article was interesting I tried finding a more specific and in depth summary of how Resolvin D2 promoted edothlial cells to produce NO to prevent the macrophages from attacking the cells. I'd like to hear other opinions on the subject. I's sure we can all agree nutrition is very important for arthritis patients. maybe we can find a more detailed summary of the pathway.

Findings may boost treatments for other inflammatory diseases, researchers say

Posted October 28, 2009

WEDNESDAY, Oct. 28 (HealthDay News) -- Researchers think they now understand the way that fish oils benefit people with rheumatoid arthritis and other conditions linked to inflammation.

The body converts an ingredient in fish oils called DHA into a chemical called Resolvin D2, which reduces the inflammation that can lead to various diseases, the scientists from Queen Mary, University of London and Harvard Medical School explained in their study published in the Oct. 28 issue of the journal Nature.

"We have known for some time that fish oils can help with conditions like arthritis, which are linked to inflammation. What we've shown here is how the body processes a particular ingredient of fish oils into Resolvin D2. We've also looked in detail at this chemical, determining at least some of the ways it relieves inflammation. It seems to be a very powerful chemical and a small amount can have a large effect," Mauro Perretti, a professor of immunopharmacology at Queen Mary, University of London, said in a university news release.

"This research is important because it explains at least one way in which fish oils can help in different types of arthritis. We can also work on this chemical and see if it can be used not only to treat or even prevent arthritis, but also as a possible treatment for a variety of other diseases associated with inflammation," said Perretti, who led the U.K. research team.

Unlike current anti-inflammatory drugs, Resolvin D2 doesn't appear to suppress the immune system, the researchers noted.

In arthritis, the body's immune system attacks healthy tissue. An important part of this process occurs when white blood cells (leukocytes) stick to the inner lining (endothelium) of blood vessels. In lab tests, Perretti and colleagues found that Resolvin D2 prompted endothelial cells to produce small amounts of nitric oxide, which acts as chemical signal that discourages white blood cells from sticking to the endothelium, thus preventing inflammation.

More information

The American Academy of Family Physicians has more about rheumatoid arthritis.

Link Between Pain Thresholds, Inflammation And Sleep Problems In Arthritis Patients

As a college student sleep is sometimes a luxury, I often find it difficult to find time to sleep with all the deadlines and daily activities. My concern for lack of sleep lead me to this lay article on RA and pain threshold for sleep disorders. I found it interesting and thought I'd share it with everyone. I thought it would be interesting to consider how sleep or more specifically sleep deprivation related to disease. can anyone think of any possible relationships between RA and sleep deprivation aside from increased stress and damage leading to increased inflammation?

Article Date: 29 Oct 2009 - 5:00 PDT

Despite recent advances in anti-inflammatory therapy, many rheumatoid arthritis (RA) patients continue to suffer from pain. Research published in BioMed Central's open access journal, Arthritis Research & Therapy found that inflammation is associated with heightened pain sensitivity at joint sites, whereas increased sleep problems are associated with heightened pain sensitivity at both joint and non-joint sites.

Researchers from the Division of Rheumatology and Pain Management Center of Brigham and Women's Hospital, and the Chronic Pain and Fatigue Center of the University of Michigan Medical School, assessed experimental pain sensitivity, disease activity, sleep problems and psychiatric distress in 59 women with RA. The researchers used questionnaires to assess the women's sleep problems and psychiatric distress and measured the levels of C-reactive protein as an indicator of disease activity. They also measured pain sensitivity with pressure pain threshold testing at joint and non-joint sites. Lower pain thresholds are indicative of higher pain sensitivity.

"Sleep problems were inversely associated with pain threshold at all sites, suggesting a defect in central pain processing", state the authors. This finding emphasises the need for research into the mechanisms underlying sleep disorders and pain in RA patients, particularly given the common occurrence of sleeping problems among these patients. This autoimmune disease, causing chronic inflammation, affects nearly 1% of the population and sufferers often report ongoing pain in spite of successful anti-inflammatory treatment.

"Since differences in pain sensitivity may shape the course of pain complaints and influence treatment decisions, it is important to understand the factors associated with enhanced pain sensitivity", lead author Yvonne Lee says, adding, "Physicians and researchers should consider both inflammatory and non-inflammatory factors when evaluating pain in research settings and in the clinic."

Notes:
The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study
Yvonne C Lee, Lori B Chibnik, Bing Lu, Ajay D Wasan, Robert R Edwards, Anne H Fossel, Simon M Helfgott, Daniel H Solomon, Daniel J Clauw and Elizabeth W Karlson
Arthritis Research & Therapy (in press)
http://arthritis-research.com/

Source:
Charlotte Webber
BioMed Central

Blood Brain Barrier Breakdown Precedes Infiltration in MS

As we discussed in class, Multiple Sclerosis is currently an idiopathic disorder with no known precipitating cause. Clinically it manifests itself as demyelinated areas of the central nervous system called lesions that contain blood derived immune monocytes. Because the immune system and the central nervous system are normally separated the immune cells are unable to discriminate between brain antigens and foreign antigens.
It is for this reason Multiple sclerosis has been considered an autoimmune disorder and therapies have centered around attempting to modify the inflammatory response and try to depress what seems to be considered an overactive immune system response. In the review article from last class by Martino and associates, it was noted that the blood brain barrier showed enhanced leakiness around the sites of the lesions but it was unknown whether this preceded or was a result of an already initiated immune response. I see this as a pivotal question to answer in the quest for a treatment of multiple sclerosis. Obviously at some point damage is done by the blood born immune system but is this behavior due to an aberrant immune response in need of correction or is it simply working perfectly against antigens that it should never have had the opportunity to encounter in the first place?
According to a paper by Floris and associates in the journal Brain, they were able to determine that in animal models with allergic encephalomyelitis (EAE) MRI imaging with gadolinium showed that vascular leakage and onset of neurological signs occurred concomitantly BEFORE the infiltration of immune monocytes. This suggests that cerebrovascular leakage and monocyte infiltration are two distinct events in the development of the lesions. This may be a very important consideration in the direction of research and the development of new therapies for multiple sclerosis.

The 1976 Swine Flu Vaccination Program

I recently read an article written by the David J. Sencer, the director of the Center for Disease Ccontrol in 1976. I found it interesting what with all of the recent publicity about the H1N1 vaccine. I have written a brief summary and added some links to the original article and to the CDC’s H1N1 factsheet.

http://www.cdc.gov/ncidod/EID/vol12no01/pdfs/05-1007.pdf
http://www.cdc.gov/h1n1flu/general_info.htm

In 1976 at Fort Dix Army base more than 200 soldiers became infected with a swine flu strain (H1N1) similar to the virus that caused the 1918 outbreak in which an estimated 50 million people died worldwide. It was decided that mass quantities of the vaccine would be needed to vaccinate the entire population to prevent a pandemic like that of 1918. The director of the CDC recommended that the federal government contract private pharmaceutical companies to produce the vaccine. A nationwide immunization program was launched by the federal government at a cost of $137million. Before any vaccine was released however, the vaccine manufacturers required that the federal government underwrite them against claims of adverse reactions prior to any vaccine delivery. The federal government agreed and the vaccinations began.

Soon cases of Guillain-Barré Syndrome were identified in patients days or weeks after receiving the vaccination. By December of 1976 more than 40 million people had been vaccinated against H1N1, of which about 500 people developed GBS. According to the NIH Guillain-Barré syndrome is a disorder in which the body's immune system attacks part of the peripheral nervous system by destroying the myelin sheath that surrounds the axons of many peripheral nerves. Sometimes it destroys the axons themselves. It usually occurs a few days or weeks after a viral infection. While there is no known cure for GBS there are treatments that can lessen the severity and speed recovery.

Statistically the number of GBS cases in the vaccinated population was higher than what would be found in the normal population in 1976 (according to the CDC about 1 more case per 100,000 that were vaccinated). As a result federal health officials decided that even the idea that GBS could be linked with the vaccine warranted ending the vaccine program immediately, so that the possibility could be investigated. In the Media the vaccination program was considered a debacle, and the director of the CDC was fired. In addition, the anticipated H1N1 pandemic of 1976 failed to happen.

According to the CDC the link between flu vaccine and GBS has been studied and in most cases no link was found. However in two studies it is suggested that 1 more person out of 1 million people vaccinated with the seasonal flu are likely to develop GBS. (http://www.cdc.gov/h1n1flu/vaccination/factsheet_gbs.htm )

Any thoughts?


More information on Guillain-Barré from the NIH at http://www.ninds.nih.gov/disorders/gbs/gbs.htm

Mystery Colors in Lymph Tissue

Since we recently discussed tattoo inks that elicit type 4 immune responses, I thought I'd mention another interesting phenomenon that arises from tattooing:
A patient presented with a lump in the right armpit that had been there for 6 months. After investigation, there could be no conclusion made about the cause of the lump. This necessitated an excision biopsy. The resulting H&E stained sample is shown above. Beyond some hyperplasia, the only noticeable defect was a black "discoloration". Immediately, it was suspected that the black spots were metastases of malignant melanoma (which is notorious for its dark pigmentation). However, after more vigorous examination and a specific, stain-based testing, they determined that this was not a melanoma. In fact, this black color was due to a tattoo that the patient had gotten 30 years previously. It has been well documented that tattoo inks end up in spleen and lymph tissue. However, it had not previously been reported that such an old tattoo could cause enlargement of a lymph node (it had been assumed that such an effect occurs within the immediate timeframe of recieving the tattoo).

Presumably, the presence of tattoo inks in immune tissues is due to uptake in the skin by antigen presenting cells which then migrate to the lymph nodes or spleen. It is interesting to note that tattoos are not only sometimes the victims of attack by the immune system within the skin, but can also cause some interesting pathology within tissues of the immune system. Since tattoo inks are not regulated, its frightening to wonder what sort of unintended chemistry might find its way into some of your body's most important defensive tissues.

That said, I'll probably still get a tattoo when I pass my comprehensive exam.


CM Jack, A Adwani and H Krishnan. Tattoo pigment in an axillary lymph node simulating metastatic malignant melanoma. International Seminars in Surgical Oncology. 2005, 2:28

Are you choosing who you are attracted to or is it your MHC region?

We know that there are many genes in the MHC I and II regions and that they are highly polymorphic. Combinations of these genes and polymorphisms are important because they are related to the number of peptides that can be presented to t-cells.
It has been shown in fish (arctic charr) that they can discriminate between MHC identical siblings and siblings with different MHC genotypes (Olsen, et al, 1997). Fish chose swimming in water scented with a sibling who had the same MHC genotypes over water in siblings who did not. In mice it has been shown that MHC genes influence individual body odor in mice and that mice also prefer MHC-dissimilar mates (Chaix, et al, 2008).
In humans, there have also been studies looking at odor preference and MHC region, although there have been no studies that have linked odor preference and attraction. In several “sweaty t-shirt” experiments women were asked their preference to smells found on t-shirts that had been worn by males with different MHC genes. Females significantly preferred the odor of males with dissimilar MHC regions to their own. Another study looked at the genetic similarity at the MHC region between spouses, which included 30 European American couples from Utah and 30 African American couples in which there was found an association between mate selection and MHC dissimilarity in the European American couples(Chaix, et al, 2008).
So if you have problems in your relationships it may not be your fault!