Back to week 3: Birth control pill is linked to heart disease?

Once again the "common folk" is a victim of the C-reactive protein (CRP) hype. A study done in 2003 showed pre-menopausal women that took birth control had twice as much CRP in their blood than women who did not take the pill. Since chronically high CRP has been linked to heart disease and inflammation and is believed to play a key role in narrowing and hardening of the arteries, it would be easy to believe the pill promotes inflammation (had we not all recently learned CRP is not the best indicator of inflammation)! However the pill has also been studied to reduce the risk of ovarian cancer due to the estrogen present.. But that's a whole other story. Pros and cons, pros and cons.

The same study revealed that even though levels of CRP were twice as high in the women who took the pill, both group's levels were considered to be in the "normal" range.

So what do we get from all this... Women currently on birth control pills shouldn’t throw them out strictly based on the fear of increased CRH levels and heart disease. Remember, heart disease is most commonly linked to other important factors such as SMOKING, diet, and genetics. Also, there are other important risk factors associated with the pill that we should be concerned with (as discussed in the discussion about stroke and blood clots linked to the pill). In conclusion, More research is necessary on this topic and hopefully next time it will include more factors besides good ol' CRP.

SOURCES: American Physiological Society annual meeting, San Diego. Darlene M. Dreon, DrPH, director of clinical research, Galileo Pharmaceuticals, Inc, Santa Clara, Calif. Trent MacKay, special assistant for obstetrics and gynecology in the Contraception and Reproductive Health Branch of the National Institute for Child Health and Human Development, National Institutes of Health.

Statistics on Countries using turmeric in food VS those that don't and the incidence of RA in these countries.

So, I was very curious after reading about turmeric being used as a spice in many Asian cultures, is there evidence showing a lower incidence in RA in these types of countries compared to the United States. I found an article with statistics of how many people are affected by RA in each country. The US has upwards of 2 millions, while some rural Asian countries are in the low thousands. I have to speculate this being because of the population difference, but it would make sense if these countries show a lower incidence of RA. The article I presented in class today shows that the curciminoids in the turmeric are very effective at inhibiting the inflammatory response causing RA problems before the RA has infected the patient. After the onset of RA there is no evidence shown that turmeric curciminoids will have any affect. So if the rural Asian countries have used turmeric as a spice in their cuisine for centuries then why wouldn't they be more prone to be effected by the inflammatory responses to RA. Maybe we should take this into account and start using more spices with turmeric. This could help our problem of millions of people in the US that suffer from RA. We could reduce this risk of RA in the US simply by putting this into our foods. This is not a totally proven way of decreasing RA but it seems to sure help. My only concern is that the turmeric curciminoids could have other effects on our body with it's inflammatory inhibitor response. It could cause us to inhibit inflammation when we really need it and just cause more problems for us. I guess this is always the issue when dealing with new ways to deal with inflammation and other diseases though.

Hey guys check out this link to an article that states that high altitude wines are more beneficial in repairing arteriole walls than low altitude wines!

http://www.jancisrobinson.com/articles/jr876

I only researched this because I recently sat next to a metabolic surgeon on an airplane and we talked the entire flight about inflammatory diseases and their relations to metabolic surgery. He was the one who informed me of the latest trends of wine drinking.

Polypharmacy

A random note about the topic of polypharmacy that we went over briefly last class:
I work at an optometrist office and sometimes I enter patient history information into the computer system, especially if we have a new patient. One of the questions on the patient history form asks the patient to list out any medication they are currently taking. This patient that I was working with needed help with that portion because she said she did not know all of the medication she was on. She said she was on "hundreds," and although that was an exaggeration, it is a good example of polypharmacy. When asked if she had some sort of list, she said "no."
Even though the likeliness of a complication arising when dealing with an eye exam is very slim, it was just a good example showing that if a patient is taking more medication than they can remember, they should always carry around a list with them.

Herbal Medicine

Herbal medicine relies on active plant chemicals with biological properties. Many conventional medicines are synthetic compounds designed to mimic the action of plant chemicals. For instance, the heart medication digoxin is derived from the foxglove plant. In herbal medicine, active chemicals are extracted from the plant parts (stems, seeds, roots, or leaves) that are the richest sources. The active chemicals can be quantitatively measured and prepared in the form of capsules, tinctures, teas, tonics, oils, or poultices. Aromatic herbs such as lavender can also benefit the immune system when used topically or as healing oils.

Inflammation is a key feature in autoimmune disease. In some conditions, such as Hashimoto's thyroiditis, inflammation contributes to the disease process. In other conditions, such as Crohn's disease, inflammation may occur as a result of the disease. Inflammation occurs as the immune system reacts to injury, infection, environmental agents, malignancy, and cellular changes. In skin, inflammation is most visible because it causes noticeable swelling, redness, discomfort and pain. The process leading to inflammation, which is known as the inflammatory response, also induces changes that aren't seen but influence the effects of inflammation and their severity.

The inflammatory response is a complex cascade of steps that include an activation of white blood cells, the release of immune system chemicals such as complement and cytokines, and the production and release of inflammatory mediators and prostaglandins. Inflammation may be acute or chronic or relapsing-remitting depending on the disease course. Most conventional treatments for autoimmune disease, including corticosteroids, work by reducing or suppressing inflammation.

Many herbs also possess anti-inflammatory (also known as antiphlogistic) characteristics. Herbs can be used as the sole therapy in autoimmune disease or as complementary corticosteroid-sparing therapies allowing patients to take smaller doses or shorter courses of corticosteroids. Treatment protocols today often rely on both alternative and conventional treatment options in a discipline known as integrative medicine.

Inflammation is a key feature in autoimmune disease. In some conditions, such as Hashimoto's thyroiditis, inflammation contributes to the disease process. In other conditions, such as Crohn's disease, inflammation may occur as a result of the disease. Inflammation occurs as the immune system reacts to injury, infection, environmental agents, malignancy, and cellular changes. In skin, inflammation is most visible because it causes noticeable swelling, redness, discomfort and pain. The process leading to inflammation, which is known as the inflammatory response, also induces changes that aren't seen but influence the effects of inflammation and their severity.

This article describes the use of plant chemicals with anti-inflammatory properties as complementary therapies for patients with autoimmune disease. Also this article I found it interesting because it gives another alternative to the consumption of NSAIDS or other drugs; the alternative way is the use of herbal products that will eventually treat the symptoms.

While researching more of the scientific articles I came to find an interesting article relating to anti-inflammatory drug use and the risk for Parkinson's disease.

Evidence from studies suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD). This study takes advantage of the well established American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort, and was able to further examine the relation between NSAID use and PD risk with more detailed information on different types of NAIDs. The cohort is a study that was initiated in 1992 to investigate the factors for cancer. Participants were from a cohort who replied to a mailed survey in 1982. In 1992 they answered a questionnaire on four types of common used analgesics. Follow-up surveys were conducted in 1997,1999, and 2001. In 2001's survey a specific question on the lifetime occurrences of PD was asked. Follow-up started on the date of return of the 1992 questionnaire and ended on the date when the first symptoms of PD were noticed for PD cases or September 30, 2001 for participants without PD.

In the '92 questionnaire, participants were asked whether they took the following analgesics regularly during the past year: aspirin, acetaminophen, ibuprofen, or other nonsteroidal analgesics. They were also asked how many days per month they took each drug, how many tablets they took per day, and the duration of use. The '97 survey asked about "baby or low dosage aspirin" and "regular or extra strength aspirin". Four baby aspirin was counted as one tablet. Users were categorized according to dosage: fewer than 2 tablets/ week; 2 to 6.9 tablets/week; and 1 or more tablets a day. Results of the study showed significant inverse association was suggested between the cumulative updated dosage of ibuprofen use and PD risk. Overall, ibuprofen users had a lower PD risk than nonusers. Unlike ibuprofen, the use of aspirin and other NSAIDs, or acetiminophen was not associated with PD risk. Non aspirin NSAID users had a 26% lower risk than nonusers.

Results were consistent with previous findings that users of non aspirin NSAIDs but no aspirin, had a lower risk for PD than nonusers. This study also further suggested that only certain non-aspirin NSAIDs such as ibuprofen reduce the risk for PD. However there is insufficient information on the optimal dosage, and it remains uncertain whether this effect is mediated by COX inhibition or through other mechanisms specific to ibuprofen and possibly some other selected NSAIDs.

The full article can be found on PubMed, the title of the article is: Nonsteroidal Antiinflammatory Drug use and the Risk for Parkinson's Disease.

Aspirin Decreases the Risk of Breast Cancer Deaths

It was revealed in February 2010 that the use of anti-inflammatory drugs such as aspirin (and other NSAIDs such as ibuprofen and naproxen) has shown to decrease the risk of dying from breast cancer. This information comes out of the Nurses’ Health Study which has followed 4,164 registered nurses who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 until their death or June 2006, whichever came first. This study has looked at a wide range of health issues in these women. In particular, they started in 1976 looking at which of the women took aspirin on a regular basis (often to reduce risk of heart attack and stroke) and have attempted to draw correlations in other health areas.

The researchers looked at the breast cancer mortality risk and the number of days per week of aspirin use (0,1,2 etc.). They found that women who took aspirin two to five days a week had a 60 percent reduced risk of their cancer spreading and a 71 percent lower risk of breast cancer death. Six to seven aspirins a week lowered the risk of spread by 43 percent and the risk of breast cancer death by 64 percent. In the end they concluded that among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death. The researchers state that more information is needed but the use of aspirin could affect tumor growth or recurrence through a decrease in inflammation.

Interestingly, it was revealed in January 2009 based on data from the Nurses’ Health Study that the use of aspirin or other NSAIDs does not decrease the risk of getting breast cancer among premenopausal women. The information from both of these papers is intriguing and points to the role of inflammation at different stages of a variety of disease states. It is likely that a baby aspirin does more than treat muscle pains, headaches and offer protection from heart disease. More information is needed however, it is promising that anti-inflammatories may have a beneficial role in decreasing mortality risk after cancer.

Holmes MD, Chen WY, Li L, Hertzmark E, Speigelman D, Hankinson SE. Aspirin intake and survival after breast cancer. J Clin Oncol 28(9): 1467-72, 2010.

Eliassen AH, Chen WY, Spiegelman D, Willett WC, Hunter DJ, Hankinson SE. Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and risk of breast cancer among premenopausal women in the Nurses’ Health Study II. Arch Intern Med 169(2): 115-21, 2009.

Identical Twins and Multiple Sclerosis

Using extremely fine-grained analytical tools, scientists compared genetic information in three sets of identical twins. One of each pair had Multiple Sclerosis, and the other didn’t — yet their genes proved essentially identical. The research cost $1.5 million, and the scientists took 18 months to sequence 2.8 billion DNA units in each twin, and determine whether they came from the mother or father. Most genomic comparisons look for differences in a just handful of suspect genes, and even whole-genome approaches don’t differentiate between parental contributions. The researchers also analyzed the twins' CD4 cells because of their central role in the development of MS. The absence of genetic differences doesn’t mean that genetics are irrelevant to multiple sclerosis. Identical twins, who are descended from the same egg, are six times more likely to develop MS than non-identical twins, who come from two different eggs. It’s still possible that some as-yet-unknown genetic factor, undetectable by even the most advanced tools, may explain the discordance in the study. However, geneticist Stephen Kingsmore thinks the culprit is probably an unknown environmental influence. This unknown factor could combine with other known genetic risks of developing multiple sclerosis. This study was a pioneering effort and the researchers are looking forward to studying more twins and other cells.

Head Trauma Linked To Alzheimer's Disease

Researchers at the University of Pennsylvania in Philadelphia are working to find out more about Alzheimer's Disease. The findings back previous studies that suggested brain trauma increases the risk of Alzheimer's disease, a leading cause of dementia, later in life. Trauma to the head may trigger a cascade of biochemical events in the brain, in time resulting in neurodegenerative changes similar to those found in patients with Alzheimer's disease. Dr. Douglas Smith says his findings support "several epidemiologic reports (that have suggested) a link between a single episode of brain trauma and the development of Alzheimer's disease later in life." Smith's team induced brain injury in anesthetized pigs via very rapid acceleration/deceleration of the animals' heads without direct impact, similar to what humans often experience in an automobile accident. Brain trauma is one of the only environmental risk factor for Alzheimer's disease, so there is something about brain trauma that might initiate these insidious neurodegenerative cascades. The analyses of the brain tissue revealed a remarkable and consistent accumulation of amyloid beta and tau proteins in damaged brain cells following trauma. In Alzheimer's disease, changes in tau protein lead to the disintegration of microtubules in brain cells disintegrating the neuron's transport system for nutrients. In the study animals, these changes were evident as early as 3 to 10 days post-injury. The team concluded that microscopic injury to the brain caused by trauma can be linked to the development of Alzheimer's disease many years after the injury. The findings may also lead to new drugs aimed at preventing the process. "This study adds to the body of knowledge that might aid us in the development of an anti-plaque-making compound," Smith said in a statement.

8 Alternative ways to reduce Inflammation without the chance of adverse effects of NSAIDs.

These are all ways of reducing inflammation without using NSAID's or other anti-inflammatory drugs. We talked about in class how COX-2 inhibitors could be linked to increased MI, and COX-1 inhibitors cause damage to you gastrointestinal system. So, why take the chance when you can just eat the right things to help you out. Omega-3 fatty acids can be consumed by taking in fish oil. There have been many studies done that show the omega-3 fatty acids make the precursors to prostaglandins, which can start or inhibit inflammation. But, remember to reduce you omega-6 fatty acid intake or you increased omega-3 fatty acid intake will not work for inflammation. The second food for you to consume is ginger. It has been proven to be a slight anti-inflammatory and helps with stomach aches and pain. The third is to take bromelain enzymes. These are seen in pineapples or you can buy them as a supplement. They are a naturally occurring anti-inflammatory. Another is Cetyl Myristoleate oil, which is seen in butter and fish. It will help with lubricating your joints and also is a natural anti-inflammatory. There was a study conducted with this oil and 63.5 % of the patients that did not respond to NSAID's for arthritic pain responded to this oil. Number five is Boswellia, which is boswellic acids that ares said to reduce inflammation. This was agreed with in a study of 175 patients with rheumatic disorders and 122 patients found reduced stiffness and inflammation in four weeks. Evening Primrose Oil was used in a study with 37 rheumatoid arthritis patients and significantly reduced tenderness swelling of the patients when only taking 1.4 g a day. Cayenne Peppers in a cream form can reduce pain by depleting a chemical component of the nerve cells that give signals to the brain about pain. The last one is White Willow Bark, in which aspirin is made out of. It gives mild pain relief and does not have the adverse effects on the gastrointestinal tract as aspirin does.

So, there's eight more things you can try to reduce inflammation before jumping the list and going straight to the medicine cabinet for your NSAIDs.

CHERRIES as treatment for inflammatory diseases

We've blogged this week about the anti-inflammatory diet, complementary and alternative medicine, and the use of NSAIDs in the treatment of inflammatory diseases... but now CHERRIES??

While looking more into the new and upcoming treatments of inflammatory diseases I was shocked to see cherries as one of these remedies!

On April 27th, 2010 a team of Michigan researchers presented a new study at the Experimental Biology annual meeting sayig there is more evidence of tart cherries' powerful anti-inflammatory benefits.

Using a "whole fool" approach, reseachers found that a cherrt-enriched diet not only reduced overall body inflammation, but also reduced inflammation at key sites (belly fat, heart) known to affect heart disease risk in obese, at risk rats. At risk obese rats were fed a cherry- enriched "Western Diet" characterized by high fat & moderate carbohydrate- in line with the typical American diet- for 90 days.

Cherry-enriched diets, which consisted of whole tart cherry powder as 1 percent of the diet, reduced risk factors for heart disease including cholesterol, body weight, fat mass and know markers of inflammation. This study offers further promise that food rich in antioxidants, such as cherries, could potentially reduce inflammation and have the potential to lower disease risk.

A 2nd study found similar results in humans. Ten overweight or obese adults drank eight ouncesof tart cherry juice daily for a month. At the end of the trail, there were noteworthy reductions in quite a few markers of inflammation, in addition to lower levels of triglycerides, another key risk factor for hear disease. Researchers say both studies are encouraging and will lead to further clinical studies in humans to explore the link between diet, inflammation and lowering disease risk.

This is the latest linking cherries to protection against heart disease and inflammation. Researchers believe it's the anthocyanins- powerful antioxidant compounds in cherries- also responsible for the fruits bright red color, that connect cherries to reduced inflammation, even inflammation related to muscle recovery post-exercise. Since cherries are available year-round in dried, frozen and juice forms, they say it's easy to incorporate them into one's daily diet to help manage inflammation.

I'd personally like to see further research in this area. I could add cherries to my oatmeal or to my yogurt as preventative care, until its confirmed factual across the board. Why not?

Just a thought...

Article can be found at:

http://www.eurekalert.org/pub_releases/2010-04/wsw/-nrr042620.php

Use Complimentary and Alternative Medicine in the Treatment of Inflammatory Diseases

In the assigned review article Anti-Inflammatory Actions of Acupuncture, the authors discussed the use of acupuncture in the treatment of inflammatory diseases. Acupuncture is one type of complementary and alternative therapy used in the treatment of various diseases. Other types include use of herbal supplements, massage, chiropractic manipulation, hypnosis, and yoga. According the National Institutes of Health, 38.3% of American adults used complementary and alternative medicine approaches and spent $33.9 billion dollars out-of-pocket for these treatments in 2007. Interestingly, the number of Americans using complementary and alternative medicine therapies has been increasing across several years despite the limited evidence to support the use of these therapy approaches. What do you think might be the reason that these therapy approaches are utilized despite the lack evidence to support their use?

Role of IFN-gamma in Alzeihmers

Reactive gliosis surrounding amyloid beta (Abeta) plaques is an early feature of Alzheimer's disease pathogenesis and has been postulated to represent activation of the innate immune system in an apparently ineffective attempt to clear or neutralize Abeta aggregates. To evaluate the role of IFN-gamma-mediated neuroinflammation on the evolution of Abeta pathology in transgenic (Tg) mice, murine IFN-gamma (mIFN-gamma) was expressed in the brains of Abeta precursor protein (APP) Tg mice using recombinant adeno-associated virus serotype 1. Expression of mIFN-gamma in brains of APP TgCRND8 mice results in robust noncell autonomous activation of microglia and astrocytes, and a concomitant significant suppression of Abeta deposition. In these mice, mIFN-gamma expression upregulated multiple glial activation markers, early components of the complement cascade as well as led to infiltration of Ly-6c positive peripheral monocytes but no significant effects on APP levels, APP processing or steady-state Abeta levels were noticed in vivo. Taken together, these results suggest that mIFN-gamma expression in the brain suppresses Abeta accumulation through synergistic effects of activated glia and components of the innate immune system that enhance Abeta aggregate phagocytosis.

Anti-inflammatory drugs (NSAID's)

During class the following two weeks we are going to talk about anti-inflammatories. Many of all, if not all of us, have used over the counter drugs to reduce unpleasant symptoms such as pain. NSAIDS work by blocking the enzymes COX-1 and COX-2, these enzymes are responsible of the production of prostaglandins. Prostaglandins are produced in the cell and promote inflammation, pain and fever. These chemicals also play a role in blood clotting and help support the lining of the stomach. However, only the enzyme COX-1 produces prostaglandins to support platelets and protect the stomach lining. Since most NSAIDS block the COX enzymes, the excessive use or chronic use of these NSAIDS can lead to stomach ulcers and bleeding. The effect of NSAIDS is determined by the amount of time it takes to be eliminated from the body and how strong it inhibits the COX-1 and COX-2 enzymes. Thus, the more a drug blocks COX-1, the greater the chance of developing stomach ulcers. Not all NSAIDS will block the COX enzymes, for example "Celebrex" will block COX-2 and will have little effect on COX-1 blockage, then reducing the chance of developing stomach ulcers or bleeding; these types of drugs are called selective COX-2 inhibitors.

Dr. Weil: The Anti-Inflammatory Diet

This week’s topic is anti-inflammatories. Many of you may have heard of Dr. Andrew Weil. He is a Harvard Medical school graduate who has been at the forefront of popularizing Integrative Medicine. He is the program director of the Arizona Center for Integrative Medicine here at the University of Arizona which he founded in 1994. Since his undergraduate career he has been interested in botany and the role plants can play in health. Interestingly, he wrote his thesis on the narcotic properties of nutmeg. However, in recent years he has concentrated his focus on different lifestyle interventions that may assist in medical treatment. One of these is the Anti-Inflammatory Diet.

Dr. Weil credits the Anti-Inflammatory diet as more of a lifestyle than an actual diet. However, he claims that “it is the blueprint for optimum nutrition”. He continues to say that simple changes in eating habits can counteract inflammation which is at the root of diseases such as: heart disease, Alzheimer Disease, Parkinson Disease, age related disorders including cancer and autoimmune diseases such as rheumatoid arthritis and lupus. At the heart of his diet plan is variety and a balance. The diet strives to balance omega-6 fatty acids (said to promote inflammation) and omega-3 fatty acids (anti-inflammatory). It recommends that we eat less meat and poultry which contain omega-6 fatty acids and eat more fish with have omega-3 fatty acids. It also aims to decrease refined and processed foods which often contain pro-inflammatory compounds called AGEs (advanced glycation end products) and have a high glycemic index. Dr. Weil’s modified version of the food pyramid depicts the Anti-Inflammatory diet’s key points very well.

I can definitely see the benefit in eating a healthy diet in order to maintain balance in our body and optimum functioning. I would say that the Anti-Inflammatory diet is a wonderful lifestyle to promote. However, I as being “anti-inflammatory”, I am still on the fence. But, it is all comparative: it is anti-inflammatory compared to the fast food nation we have become with diets high in saturated fat. Looking over the pyramid, the way of eating appears to be much more similar to our hunter/gatherer past with a greater emphasis on fruits, vegetables and fish and sparse consumption of poultry, red meat and sweets. Take a look for yourself and let me know what you think: http://www.drweil.com/drw/u/ART02012/anti-inflammatory-diet

Medications Used in the Treatment of Alzheimer’s Disease

I had discussed in the class the research that is being conducted regarding the relationship between fibrin and Alzheimer’s Disease. I was interested in finding the current medications that are used in the treatment of AD, and came across an article from a PhD student, Carrie Hill. We know that there is no current cure for AD, which is why studies like I discussed in class are being performed. There are, however, medications that improve symptom management of the disease. When developing treatment plans, the cognitive and behavioral symptoms are considered.
I wanted to focus on cognitive symptoms, which include problems with thought processes like memory, language, and judgment. Cholinesterase inhibitors and Namenda are two kinds of medications that have been approved by the FDA for treating these symptoms. Cholinesterase inhibitors increase the levels of acetylcholine in the brain, which plays a key role in memory and learning. Surprisingly, this alone can postpone the worsening of symptoms for 6 to 12 months in about half of the people who take it. Cholinesterase inhibitors are most commonly prescribed for mild to moderate Alzheimer’s disease. Namenda, known as memantine, regulates glutamate in the brain, which plays a key role in processing information. This drug is used to treat moderate to severe Alzheimer’s disease and may delay the worsening of symptoms in some people.
Cholinesterase inhibitors can be started as soon as Alzheimer’s symptoms appear, and are most effective in the early stages of disease. When a physician determines that the cholinesterase inhibitor is no longer effective, memantine is usually introduced. Sometimes, memantine and a cholinesterase inhibitor are taken simultaneously during the moderate stage of the disease. I wonder if this combination with the addition of anti-inflammatory drugs would show a decrease in the progression of Alzheimer’s Disease?

http://alzheimers.about.com/od/treatmentofalzheimers/a/treatments.htm

Multiple Sclerosis: A Causative Analysis

As we've already read in class, many researchers are looking at what they believe is/are the cause/s for the development and full expression of multiple sclerosis. We read a paper on microglia changing its phenotype to a cell somewhat identical to a phagocyte, and past research focuses have been on T cells. This condition is commonly referred to as an autoimmune response to some protein of the myelin sheaths, though this is still debatable. Current treatment can attenuate the response and lesson the symptoms, but there is no way to target any chemical treatment to the nervous tissue without effecting the entire immune system and its cells--so attenuating the cells of the immune system pharmacologically if a patient with MS also attenuates any immune response (depending on the compound used). The research of MS is further confounded by research models. Currently, rate or mice are generally used; however, since the cause of the disease is unknown, we cannot accurately say that the animal models are expressing the disease to the same or similar extent.

The affected tissue lies deep within the brain, forbidding any manual intervention that would not cause unknown irreversible consequences. Recent research has been done on the assumption that MS spontaneously begins with auto-reactive T cells, and this is supported by the mice models which much be injected with nervous tissue to develop the disease. Countering this idea is a group of scientists who have developed a murine which spontaneously develops MS. All murine models of MS have not been able to show B cell involvement, except this new model. The group found that yes, T cells are active in the model, but they are not actually inducing disease...B cells induce MS (shown by general good health in these models when B cells are removed). This is not to say that B cells are the prime player. T cells can do plenty of damage in the brain, but antibodies may be needed to sustain and develop the disease.

I just found this research interesting, and linked the paper's title above. I still feel it's important to take this with a grain of salt, simply because this is one study, published recently, in a species other than our own with a disease that is still not understood fully and may not completely represent how we express the disease. There's obviously a lot of research to do, but it's so very interesting to read about these finds which go against what the topic's body of research says.

The role of glial cells in Parkinson's Disease

The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In Parkinson's disease, postmortem examination reveals a loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the propagation and perpetuation of neuronal degeneration. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF-α, Il-1β, IFN-γ), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase-3 and caspase-8, which are known effectors of apoptosis, has been reported in Parkinson's disease. Yet, caspase inhibitors or invalidation of TNF-α receptors does not protect dopaminergic neurons against degeneration in experimental models of the disease, suggesting that manipulation of a single signaling pathway may not be sufficient to protect dopaminergic neurons. In contrast, the antiinflammatory drugs pioglitazone, a PPAR-γ agonist, and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease.

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AD-Cholesterol Connection

As I had mentioned in class, there has been an establishment of cholesterol as a risk factor in the pathogenesis of Alzheimer’s disease (AD). This is a major focus of current research for AD. I came across a review article from PubMed titled, Alzheimer’s disease: the cholesterol connection, and found that in the past few years, this link has been supported through genetic, epidemiological and biochemical data. The review was from Harvard Medical School’s Neurobiology of Disease Laboratory and Genetics and Aging Research Unit.

In all forms of Alzheimer’s disease (AD) there is an abnormal accumulation of the beta-amyloid protein in specific brain regions, which is regulation by cholesterol. It was found that elevated levels of cholesterol increase the beta-amyloid protein in cellular and most animal models of AD, and that drugs that inhibit cholesterol synthesis lower the beta-amyloid levels. Recent studies have shown that the total amount and distribution of cholesterol within neurons impact the beta-amyloid biogenesis. I mentioned in class the role of the apolipoprotien E gene, the identification of a variant of this gene as a major genetic risk factor for AD is consistent with a role for cholesterol in the pathogenesis of AD.

The review describes its recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection. Drugs that lower cholesterol levels are currently being considered and tested as potential therapies for the treatment of AD. Statins, which are relatively safe and have been used for a long time against high cholesterol levels, are now being directly tested in clinical trials for efficacy against AD. Some of the potentially beneficial effects of statins might also represent improved cardiovascular health, resulting in a reduction in ischemic events that are also considered risk factors for AD. An effective therapy for patients whose cognitive function does not benefit from statin treatment may ultimately consist of a combination of lipid regulating products, perhaps in combination with statins. Alternative products for cholesterol management so far include extended-release niacin, cholesterol absorption inhibitiors, ACAT inhibitors and cholesteryl ester transfer protein (CETP) inhibitors. Results from in vitro studies suggest that ACAT inhibitors are good candidates for regulating beta-amyloid biogenesis, but more research is needed to understand the exact molecular mechanisms underlying the AD-cholesterol connection. Also, it is necessary to gain an in-depth understanding of brain cholesterol metabolism. With new technology that is developing, we may be able clarify how plasma and brain cholesterol contribute to AD.

Full PDF text found at EBSCHOhost:
Title: Alzheimer's disease: the cholesterol connection.
Author: Puglielli, Luigi; Tanzi, Rudolph E.; Kovacs, Dora M.;http://web.ebscohost.com/ehost/pdfviewer/pdfviewer?vid=2&hid=106&sid=86523406-21ed-4ee6-8f03-87d50b8af3df%40sessionmgr110

Sunlight (UV) and Multiple Sclerosis?

As I mentioned in class, the 2010 CDC study found a correlation between areas of highest MS prevalence and greater UV exposure. I've chosen to explore this idea and I've found an article which I've referenced below which discusses an exploration of this trend:

For some time now, the observation that MS prevalence increases with latitude, meaning the further from the equator one gets, the higher likelihood of MS in the environment. Researchers in this article therefore look at Vitamin D and how its levels may in these different latitudes may help explain the differences in prevalence.

The article notes that 400,000 people in the U.S. have MS, of nearly 309, 055, 803 people in the U.S. (U.S. Census Bureau). UV exposure, as well as vitamin D levels can effect immune responses, but the question which arises is whether immunoregulation is done via UV exposure, or indirectly via vitamin D levels, or the two? As referenced in the article, research somewhere (not cited) has shown that increased levels of the active form of vitamin D can "block" the disease in animals.

The experiment uses mice which are genetically predisposed to an MS-like disease state, and the mice are injected with nerve antigen to initiate the disease. After initiation, one group of animals were exposed to "moderate" UV strength (equal to 2 hours of direct summer sun) for one week and the other group was irradiated every 2nd or 3rd day. They found that the exposure reduced the expression of symptoms for MS, but not the prevalence, especially in those mice irradiated every other day. The researchers also deduced that although vitamin D levels were increased with UV exposure, that factor alone could not explain the results.

The groups next area of study is to see what role skin may play with UV exposure to the production and expression of compounds involved in inflammation and the inflammatory response. The article identifies two possibilities of usefulness:

1. In the short term, if they can identify the specific active wavelength at which these same results can be obtained, this can be used as a therapy for those people suffering from MS.

2. In a more long term goal, if the group can discover the compound or compounds that the skin may be producing, the may be able to isolate or synthesize the compound and market a drug treatment.

The group does caution that this information is in the early experimental stages of development, and that results of a similar treatment may not lead to intentions.

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