Glucosamine and obesity....a bad combo?

In tying some of this together with some of our past topics, I found a study done published in 2007.  The article is entitled, Oral glucosamine in doses used to treat osteoarthritis worsens insulin resistance. 

link:     http://zp9vv3zm2k.ssscom.ezproxy2.library.arizona.edu/?V=1.0&pmid=17570985

  As we covered earlier this semester, obesity can be a highly inflammatory process.  Also, we know that obese individuals typically present with abnormal blood glucose levels and eventually may have serious complications/morbidities stemming from insulin resistance. 

  An overweight or obese status can lead to increased strain and over time wear and tear on the joints of the body.  Therefore it may be common today due to the advertising of OTC joint formulas (such as glucosamine) for an obese individual to be taking these on a daily basis.  According to these researchers, glucosamine taken to treat osteoarthritis may be aiding the joints but it may also be detrimentally worsening vascular function and insulin resistance.  Results such as increased LDL, decreased small artery elasticity, and an increase in fasting insulin and glucose resulted in testing of individuals taking oral glucosamine for six weeks.  It should be noted however the these participants in the study were not ruled out for many reasons: " Exclusion criteria were myocardial infarction within the last 6 months, taking medication within the previous 6 weeks known to affect glucose metabolism, and past use of glucosamine within 1 year."  Therefore these participants could have had multiple conditions that may have some other effects but baselines were taken from each prior to starting the study. 

  So, it would appear that supplemental glucosamine may have some other factors to monitor beyond just the joint areas.  Once again...use with caution and a little common sense in all areas of your life.

Acupuncture for Surgery?

I was chatting with one of the Physical Therapists I volunteer with the other day about acupuncture and Chinese medicine, and since we discussed about acupuncture a little in class, I thought I would find out more info about one of the studies he brought up to me.

As we all know, this stuff has been around for thousands of years.. but how exactly does it work? One theory says that the acupoints of stimulation are points of designated sensitivity. Putting needles at these points stimulates sensory receptors, increases blood circulation to that point, receptors stimulate nerve impulses to hypothalamic-pituitary system, and subsequently releasing neurotransmitters and endorphins. Acupunture has been used for various treatments such as relieving headaches, muscle spasms, pain, inflammation, and drug addiction. But one study that caught my eye was the use of acupuncture for anesthesia during open heart surgery in China.

Using acupuncture for open heart surgery was introduced decades ago in China, but interest in this method has resurfaced due to the increasing cost and maintenance of surgery. This study (Acupuncture anesthesia for open heart surgery in contemporary China –Jia Zhou, et al) , designed from various scientists from China and the US, was conducted from July 2006 to October 2010. 100 patients had open heart surgery while under combined acupuncture-medicine anesthesia (CAMA), while the second group was under conventional general anesthesia (GA). Results of the surgeries showed that although CAMA group had a longer operation time, they had a lesser usage of narcotic drugs, a significantly lesser incidence of postoperative pulmonary infection, were able to eat and move about sooner than the GA group, and had shorter intensive care and hospital stay. Overall, the CAMA group had a lower surgical total cost than the GA one.

So what does that mean for the future of medicine? Do we look more into Eastern medical treatments or do we continue with our research in pharmaceuticals and synthetic mechanisms? I know that it is difficult to study and determine whether acupuncture was really the reasoning for a patient’s improvement, or whether it was just a placebo effect, but either way I feel that as this trade has been around so long, that there must be some kind of benefit from it. I personally find some Eastern medicine fascinating and think it would be worth it to invest more time in looking into this methodology, rather than always relying on pharmaceuticals and resulting in potential side effects.

http://www.ncbi.nlm.nih.gov/pubmed/21570137

Renal effects of NSAID use

So far, the major complications associated with NSAID use appear to deal with the gastrointestinal lining and liver. However, since all the systems work together, this class of drug surely has an effect on other organ systems, as well. We have seen recently that most NSAIDs work through inhibition of the production of prostaglandins. While this family of mediators is often associated with pain and fever, prostaglandins have other regulatory roles in the body that are undoubtedly affected if they are down-regulated. One such role is in the kidneys, where the prostaglandin family is involved in both the regulation of sodium reabsorption and activation of the rennin-angiotensin system during periods of decreased renal perfusion.

In healthy individuals, the renal effects of NSAID therapy are mild because kidney function is not dependent on the presence of prostaglandins. However, in patients with compromised renal perfusion, the down-regulation of the prostaglandins can result in various systemic issues. The most common kidney related side effect of NSAID use is peripheral edema. Without prostaglandins to inhibit sodium reabsorption, water is retained in excess. This may lead to edema, weight gain, and could aggravate preexisting cardiovascular problems due to an increase in plasma volume.

I believe the review posted below does a good job linking together various systems that are affected by NSAID use. If anyone finds articles or studies implicating NSAID use with defects in other systems, please post them here.

Here is the review talking about the effects of NSAIDs on kidney function and the mechanism behind it:

http://www.medscape.org/viewarticle/422939_3

Capsaicin

After having a discussion on turmeric last week, I was interested in looking for other alternatives to NSAIDs. While doing some research, I came across a website that discussed the pros and cons to certain NSAID alternatives. One listed here was diclofenac, which is one of the alternatives we will be discussing in class today, but the one that I wanted to focus on was capsaicin and how it affects the body.
Interestingly, capsaicin is known for depleting substance P within our body. Substance P is a neuropeptide that is associated with pain and inflammation. Capsaicin interferes with the retrograde transport of NGF to the cell bodies of sensory neurons and in doing so, it results in decreased synthesis of substance P. Decreased concentrations of substance P means less pain.
I would like to know if capsaicin is in fact, an alternative to NSAIDs in treating symptoms. After looking around for some studies regarding this, I was unfortunately only able to find studies that discussed the depletion of substance P, but in regards to blocking respiratory rhythm in neonatal rats in vitro. If anyone knows of, or finds a study dealing with capsaicin, its efficacy, and the placebo effect studies, please post.
Here are the two links that I was talking about earlier:
1. http://www.kevinmd.com/blog/2011/02/alternatives-nsaids-pros-cons.html
2. http://www.ncbi.nlm.nih.gov/pubmed/2581820

Tuft's Newletter

Fellow students,

As we conclude our semester, I would like to provide a source that I find particularly useful in translating scientific research into everyday language. Especially if you want to direct anyone asking you questions about healthy living, this is a good source to direct them to.

http://www.tuftshealthletter.com/

Tuft's Newletter is published by The Friedman School of Nutrition Science and Policy at Tufts University in Boston, MA. They have tabs for Nutrition, Weight Control, Memory, Vitamins and Supplements, etc. Some of their articles do cost money ($1.95) but there are plenty of free articles, as well.

It may be a little too simple for most of you but I do find it to be a great place to direct people asking me about sources for healthy eating or exercise. The writers basically translate the research into basic language so non-science people can understand.

2 birds with 1 stone

While I was researching Curcumin, I thought this website was really cool!!! Students at the Stanford University created a club called HOPES (Huntington’s Outreach Project for Education, at Stanford). This club is dedicated to making scientific information on Huntington’s disease (HD) readily accessible to primarily educate the public on HD, as a reliable source. (https://www.stanford.edu/group/hopes/cgi-bin/wordpress/2010/06/curcumin-the-curry-spice/).

HOPES recognizes Curry (Curcumin; a turmeric, part of the ginger family) and devotes a whole webpage (updated June 2010). First a comparison of the prevalence of AD between Indian and American populations is done. It is found that India has 1% of their population over the age of 65 live with AD and the people between the ages of 70-79 in Inida are one fourth as likely to develop AD as Americans are. Nevertheless, the diet intake of Curry is recognizably different between American and Indian populations, and was studied and discussed. Through recent scientific findings of how curcumin affects on the nervous system, it is known that curcumin can help prevent and alleviate Alzheimer’s disease (AD) (although they bring up so uncertainties in the data they referenced). HOPES suggests that since the neurodegeneration pathway is “strikingly similar” in both AD and HD, than it is fair to say that Curcumin administration would help alleviate or slow the progression of each disease due to its natural NSAID-like inhibiting characteristics (decreasing inflammation and oxidative stress(OS)). Reducing the use of NSAIDs.

The causes between AD and HD are is that HD is genetic and AD is both genetic and environmental. These neurodegenerate diseases are caused by inflammation and OS leading to nerve cell damage causing a buildup in beta-amyloid plaque (BAP) in AD and Huntingtin protein aggregation (HTT) in HD. The Stanford students believe, based on what they know anyways, that any substance that has been shown to decrease beta-amyloid plaque (BAP) should have a high chance to decrease HTT. They finally conclude,

“However, while this possibility is certainly a source of intrigue, it is important to note that not all substances that are proven to decrease [BAP] levels have shown the same effectiveness with [HTT].”

This is where Curcumin comes in the picture. The website is hopeful that someday Curcumin studies on HD will show promise to decrease HTT aggregates, in the meantime they believe Congo Red and thioflavine S have been effectively shown decrease both BAP and HTT.

Although I like this idea of student-run website to educate others on HD, but is this website citing correctly? I just honestly had a hard time believing if everything is referenced correctly.Would this be considered a reliable and credible source for correct scientific knowledge? Anyway do you think substances like Curcumin, that have been shown to treat AD (and Rheumatoid Arthritis), have a shot at treating a genetis disorder like HD based on its somewhat similar pathology? I would like to see if any other turmeric has been studied like this? Last but not least, how and why do other substances like Congo Red and thioflavine S, have the same physiological abilities as Curcumin? 

Glucosamine: True or False?

So the most common type of arthritis is Osteoarthritis (OA). OA is a type of degenerative disease of the inflamed joints. Although it is acute inflammation, aging or wear-and-tear help progress degeneration of the cartilage, in turn developing bony spurs within various joints. Some risk factors of OA are trauma, aging, and obesity. The target of treatment is to somehow relieve pain. While using NSAIDs, they have been linked problems increase GI riask and CVD risk based on Monday’s review. An alternative thought was to use Glucosamine Sulfates (GS).

The theory behind using GS is to rebuild and maintain the cartilage function. This has been popular for some time as a treatment for OA. First, Glucosamine is the amino sugar that is believed to support the formation and repair of cartilage to decrease swelling and possible breakdown. This kind of medication is natural (found in seashells) . While researching Glucosamine studies, I found many mixed reviews about Glucosamine, this website (http://senior-health.emedtv.com/glucosamine-and-chondroitin/is-glucosamine-and-chondroitin-safe.html), I think gave overview of the possible side effects of the supplement. Nevertheless it is still known that Glucosamine maybe effective in treating and perhaps slow the progression of OA. (Another good article that disagrees with Glucosamine Sulfate is by Dr. Stephen Barrett, Glucosamine and Chondroitin for Arthritis: Benefit in Unlikely).

 I found one Clinical Study called, “A clinical study on Glucosamine Sulfate versus Combination of Glucosamine Sulfate and NSAIDs in Mild to Moderate Knee Osteoarthritis” (http://www.tswj.com/2012/902676/). The aim of this study is to explore the differences between glucosamine sulfate (GS) versus combination of  GS and NSAIDs in patients with mild-moderate knee OA. After the patients are diagnosised with mild or moderate Osteoarthritis. They used two different methods to collect data via the, “Western Ontario McMaster Universities Arthritis index (WOMAC) of Osteoarthritis questionnaires and Visual Analog Scale (VAS).” WOMAC assesses pain, stiffness, and physical function in patients with hip and / or knee osteoarthritis and VAS assesses the body’s efficacy of pain management. The results based on these test scores show that at first the combination of GS with NSAIDs demonstrated better improvement in pain, stiffness and physical function, in comparison with just GS. However, at their second review the results revealed that GS group also showed great improved in pain, stiffness and physical function, but not as well as GS and NSAIDs in that same time.

I really enjoyed reviewing this study and even though the study suggested that the “Glucosamine Sulfate has a carryover effect like disease modifying agents.”  Could the long-term treatment  use of  GS reduce the need of NSAIDs?  In the study, 18 of their subjects did not go through with the experiment due to poor compliance, GI problems, and Inadequate control of pain. What I found interesting is even though the goal is to reduce the NSAIDs side effect and improve the patients quality of life,  the data shows that the pain treatment is better much with combination of NSAIDs and GS, but they claim that glucosamine sulfate may reduce the dependence of NSAID usage and delay the disease progression. This doesn’t really solve the problem, but there have been many websites that promote the combination of GS and NSAIDs… So does Glucosamine even matter? What do you think?

Omega 3 + NSAIDs = ???

Discussing the different types of NSAIDs in the articles reviewed on Monday, I was wondering why is there  any other form of alternative medications, that help assist witht have the GI or Heart Failure that appears to be attached. I researched this and stumbled upon Anti-Inflammatory natural essential fatty acids Omega-3 and omega-6. Since our bodies don’t produce these fatty acids, they are obtain through or diet or supplementation. There are two essential omega-3 fatty acids, (eicosapentaenoic acid, called EPA and docosahexaenoic or DHA), that the body needs. To learn more about omega threes these websites were very useful to me http://www.jomo.com/program-omega3-and-bone-joint-health.html and http://www.umm.edu/altmed/articles/omega-3-000316.htm .

Joel M Kremer of the American Journal of Clinical Nutritional, find that taking Omega 3s after about a 12 week period of time could help patients with rheumatoid arthritis (http://www.ajcn.org/content/71/1/349S.full) and the study title is (n-3 Fatty acid supplements in rheumatoid arthritis). He found that when patients were on Omega 3s or n-3 fatty acids, it has been shown consistently to reduce both the number of “tender joints on physical examination and the amount of morning stiffness” in patients with rheumatoid arthritis. In his method of research, the omega 3 supplements were taken daily with other prescribed medications. After about 12 weeks the benefits of omega threes became apparent, and appeared that a minimum of 3 g eicosapentaenoic and docosahexaenoic acids a day “is necessary to derive the expected benefits.” What was cool is that these doses of omega-3 fatty acids are linked to reductions of leukotriene B₄ (neutrophils) and interleukin 1 (Monocytes), instead of inhibiting the the enzyme COX. Besides COX, these are other inflammatory mediators are thought to cause and progress most cases of RA. Through his references, there were several investigators observed that rheumatoid arthritis patients consuming omega-3 dietary supplements were able to lower or discontinue their background doses of NSAIDs or disease-modifying anti-rheumatic drugs.

All in all, this study wasn't really confirmatory or definitive to settling the issue of substituting medications, this is because the methods here variable and exclusive to RA patients. I just find it crazy that not only do omega-3 fatty acids have virtually no reported overdosage/serious toxicity they are very well tolerated when used to treat RA patients. Therefore (as the study concluded) the dietary supplement should not replace NSAIDs totally, but is highly recommended to be added to any diet. On the other hand, Kremer says “After taking n-3 fatty acid dietary supplements for 3–4 mo, patients may try reducing their NSAIDs dose under the supervision of a physician.” My follow up question would be why is it only patients with rheumatoid arthritis being studied here? Also, do you think they can create some supernatural anti-inflammatory medication with both NSAIDs and these forms of natural remedies?

Mechanisms for Advil and Tylenol Side Effects

Hello all physiologists:

That article "How Safe are Tylenol and Advil? Helping Patients Sort Out the Risks" was such a terrible article, whose main point was just listing the negative side effects of each product and then arguing which product is better based on their respective negative side effects. In the article it said the Tylenol (acetaminophen) when overdosed on causes liver failure, and Advil (ibuprofen) when overdosed causes stomach bleeding and ulcers. However, it doesn't explain the mechanisms that transpire in order for these effects to take place, and instead the article basically ends by saying so long as you don't overdose on these products they are both perfectly safe... To which I would like to add DUH!

Wanting more information on both products and their side effects I went looking around for some answers and found to good sites that explain each products negative side effect mechanism. In the case of Advil, it is an anti-inflammatory that blocks both cyclo-oxygenase enzymes (COX-1 and COX-2). Both these enzymes have the same affinity to convert arachidonic acid to prostoglandins which then go out and cause various effects based on what the enzyme's function is. For COX-2 this function is to induce inflammation, and according to the website I looked at it is not present at baseline but increases and is inducible by inflammation. COX-1 on the other hand, possesses multiple functions one of the most important is maintaining the stomach lining. Thus, We can see why we see stomach bleeding in those who overdose on Advil, because if COX-1 is inhibited too often, the stomach lining gets weak and the gastric acids are able to eat away at the stomach wall causing ulcers, and in worst case scenarios stomach bleeding.

As for Tylenol (acetaminophen), this one is more interesting because Tylenol isn't an anti-inflammatory, it's just an analgesic. So if that's the case than why does it cause liver damage? According to the site I found it turns out that after Tylenol is metabolized it activates the nuclear receptor CAR which induces the expression of three cytochrome P450 enzymes that transform acetaminophen into NAPQI, which is a reactive and toxic metabolite. This is normally detoxified in the liver, however when one overdoses on Tylenol the NAPQI becomes to abundant for the liver to detoxify and thus the metabolite causes severe damage to the liver.

One last note, I would just like to say that the two sites you are about to visit, or not, have good information but not complete information. I think they cover enough basics which allow a person to understand the mechanism that is occurring with overdose of these drugs, but at the same time I think they have some gaps in their information that they could have filled in more. Other than that, please enjoy the websites and fill yourselves with knowledge. Also leave any comments you have below.

http://www.arthritis.co.za/cox.html
http://www.biocarta.com/pathfiles/h_AcetaminophenPathway.asp

Misdiagnosing Alzheimer's

When we reviewed week’s lay article about “New hope for Alzheimer’s sufferers after new treatment ‘restores memory in minutes’”, it reminded me of an episode of Body of Proof that I had watched over winter break. Long story short of the episode, among the drama of a murder of course, one of the family members of the victim was being treated for Alzheimers, but the protagonist doctor discovered that he was actually misdiagnosed for a CSF buildup (if I recall correctly), gave him medicine, and he was recalling memories instantly.. So I wanted to see if this was a real thing and not something that Hollywood made up!

 Normal pressure hydrocephalus (NPH) is the name for this abnormal cerebrospinal fluid buildup. It is often misdiagnosed as other diseases such as Alzheimer’s or Parkinson’s due to overlapping symptoms such as difficulty with walking, urinary inconsistence, or cognitive changes. Under certain conditions, some patients are candidates for surgical treatments, allowing more flow of the fluid and in turn allow those patients to regain some of the functioning that was lost. (http://www.webmd.com/brain/normal-pressure-hydrocephalus)

I could not find, however, how quickly one would regain that cognitive ability. I’d imagine that with surgery, it would take a while before regaining memories or complete physical activity. In regards to the lay article, I feel that if Enbrel really was a miracle drug and allowed patients to regain their cognitive ability so quickly, we would hear about its use a lot more.  The one thing I found interesting in both circumstances was the importance of flow to the brain: CSF in NPH, and blood flow to the brain ‘where the drug is designed to block a chemical responsible for inflammation’ with Enbrel. I now question whether the subjects in the Enbrel article were confirmed with a brain scan as Alzheimer’s patients or whether it was a misdiagnosis and a coincidence that these results were found.    

Resveratrol's effect on Colitis

For those of you that do not know, Resveratrol is an extract taken from grape seed and wine, and is considered to be a potent anti oxidant. One of the lay articles suggested to readers that if they have inflammation, then increasing their grapes/wine consumption may be beneficial. I decided to look into how beneficial reveratrol is as an anti inflammatory, and found some interesting information. I found an article relating the beneficial use of reveratrol to the decrease of symptoms in patients presenting with Colitis.

Article: http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0706469/full

Remember that colitis is contributed to neutrophil activation, cytokines, and oxidative stress. According to experts, reveratrol reduces inflammation and ROS. This article wanted to show that resveratrol can help patients with inflammatory problems. The findings concluded that the over the counter supplement corrected morphological problems, reduced pro inflammatory cytokine expression, stimulated apoptosis in colonic cells, and reduced levels of oxidative stress.

There are many other reasons to increase grape, wine, or supplement consumption of resveratrol. Information of this can be found here: http://online.liebertpub.com/doi/abs/10.1089/152308601317203567

Ethan Burns

The Dangers of NSAIDs

I was interested in learning about some of the negative effects of NSAIDs, as many of us don’t hesitate to pop a couple of pain-relieving pills at the first sign of aches and pains. While non-steroidal anti-inflammatory drugs (NSAIDs) offer many benefits, the side-effects to regular use of these drugs are often unmentioned because of their widespread availability and seemingly low danger.

According to a review by the American College of Gastroenterology, the regular use of NSAIDs is the second major cause of gastrointestinal ulcers. In addition, taking NSAIDs with alcohol increases the risk of this intestinal bleeding. This poses a frightening danger as the first thing most people reach for after a heavy night of drinking is a bottle of Asprin. Others may even finish the night off with a few aspirin to preemptively combat the looming hangover.

Some sources state that acetaminophen (Tylenol) causes less upper intestinal irritation than Naproxen (Alleve) and Aspirin (Bayer), but a combination of alcohol and acetominophen can lead to liver failure in some cases. So next time you wake up with a raging headache after a long night of boozing, maybe reach for a gatorade and some coffee instead of the pill bottle.

So my question to you guys is how dangerous do you think NSAIDs really are? Do the side effects really only effect those who are predisposed to intestinal/liver damage or are we all at risk?

Here is the review by the American College of Gastroenterology:

http://patients.gi.org/topics/aspirin-and-nsaids/

The Neuroimmune Basis of Anti-inflammatory Acupuncture

Acupuncture refers to a family of procedures that involves the stimulation of specific anatomical points throughout the body. It is considered one of the oldest healing practices, and is categorized as traditional Chinese medicine (TCM). Its origin dates back to the Neolithic Age (8000 - 5000 BC) in China. This has been practiced for thousands of years in many other Asian countries, in addition to China. Recently, it has started to flourish in Europe and the United States.
The idea behind acupuncture according to TCM, is to keep the flow of Qi (pronounced chee), which is considered the body's vital energy, undisturbed throughout the proposed 12 primary channels in the body. These channels are known to connect the 360 principle points that are within the body. This is because it is believed that the body should be in balance with the opposing, inseparable forces: yin (passive principle) and yang (active principle). Therefore, if there is an imbalance between the flow of Qi, the idea is to stimulate one of the principle points associated with the blockage to unblock the channel, restoring balance. According to the NHIS, between 2002 and 2007, it is estimated that 4.1 million U.S. adults had used acupuncture.
Fortunately, there have only been a few complications associated with the use of acupuncture that have actually been reported to the FDA. The biggest concern comes from inadequate sterilization of needles and from improper delivery of the treatment. The safety precautions are making sure that a new set of disposable needles are used every time, as well as having a qualified, licensed practitioner. Certain complications include infections and punctured organs.
After reading this article, I was not anymore convinced about trying acupuncture because the efficacy of this procedure still remains to be controversial and biased. Although there have been some experiments whose results support the benefits of acupuncture, there seem to be more results that remained inconclusive. What are your thoughts regarding the efficacy of acupuncture and if someone has had acupuncture, do you believe it actually worked/helped?

Stroke can change person's sexuality?

This is a kind of epic news that talks about how stroke can possibly change your personality, skills, accent, and even sexuality when you suffer unconsciousness from a stroke and someday you just wake up. Apparently, this Australian guy, who is 26 years old, woke up from unconsciousness turns out to be gay although he was engaged with his girlfriend.
I did not notice that stroke can change your personality including sexuality. Mostly when you have a stroke, your body gets partially or mostly paralyzed because a lack of blood flow to your brain usually happens.However, interestingly enough it can also have symptoms of personal mind as well.
Check this article follow the address below:

http://www.heraldsun.com.au/news/more-news/footy-player-woke-up-gay-after-stroke/story-e6frf7lf-1226331700724

Huntington's Disease

I wanted to talk about a neurodegenerative disease that we didn't discuss in class. If anyone watches/watched House- 13 (Olivia Wilde's character) was genetically predispositioned for Huntington's Disease because her mother died from it.

Huntington's is a neurodegenerative disorder characterized by both psychiatric, physical and cognitive impairment. It can be diagnosed early in life for those with genetic history of the disease as it features a repeating -CAG- pattern on the huntington gene, resulting in misfolded proteins.

Reactive oxygen species play a big role in neurodegenerative diseases and the inflammatory response, as we have learned in class. Antioxidants work by scavenging the free radicals, essentially blocking them from causing damage. This study looks at a whole bunch of antioxidants and how they could be potential treatment for slowing the progression of HD.

http://www.ncbi.nlm.nih.gov/pubmed/22138129. You can find the full article by typing "Antioxidants in Huntington's Disease" into the Library journal search and clicking out to electronic sources.

I decided to look up Lou Gehrig's disease today since all I knew about it was that it was a neurodegenerative disease and it is named after an American baseball player that was diagnosed with it in 1939.  Consequently, it is know as motor neurone disease in Britain.  Anyways, after reading a few articles on the disease, which is officially know as amyotrophic lateral sclerosis, I found that that very little is known about the actual cause of the disease, except that it is hereditary in about 10% of the total cases and that 5 in every 100,000 people are affected by ALS.  The genetic cause can come from an inherited defect that is located on chromosome 21, which is seen in about 20% of known family related cases.  It is also thought that the mutation is Autosomal dominant.  More on the genetics can be found at http://web.archive.org/web/20041115214832/http://www.alsphiladelphia.org/pennstatehershey/newsletters/newsletter_spring04.htm.
There are also a few cases in which development of ALS may be linked to chemicals, with a study from 2000 showing that employees at a chemical company which were exposed to 2,4 - D had an increased mortality rate from ALS.  This is the study (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1740039/pdf/v058p00024.pdf)
It is also interesting to note that Italian soccer players have a 5x higher incidence rate, which has led some to suspect the pesticides used on the field grass.  Also, the ALS association has said that US military veterans are at an increased risk of developing ALS as well.
    The disease causes the the neurons in the body to waste away and die, which causes progressing muscle weakness and loss of motor control.  This continues until the patient is unable to breathe on their own.  Along with the loss of muscle use and control comes everything that you would expect, ranging from paralysis to an inability to speak.
   There are no permanent forms of treatment at the moment though some progress has been made in slowing the disease, if only for a few months.  Most treatment is currently focused on relieving the painful and debilitating symptoms of the disease that are associated with the destruction of the neurons.
   The the prognosis is grim at the moment, it is promising that there have been successful attempts at slowing the disease.  More on that here:  http://www.architalbiol.org/index.php/aib/article/view/1267

Can you guys find anymore promising treatments or theories on this disease?

Alzheimer's Disease Prevention

This article discusses individuals who are at higher risk for developing AD later in life, and preventative measures that can be taken in order to decrease the risk factors involved.

http://www.medscape.com/viewarticle/488849

A very interesting point the article brought up was that high blood cholesterol levels and diabetics are at higher risk for AD. This brings up an interesting question. In a nation that relies so heavily on fattening food and suffers from cholesterol problems, what will the levels of AD be like in 30,40, even 50 years from now? I wonder if McDonalds will still be advertising in front of their entrances, "billions and billions served...

Since it seems from this page that the primary problems are associated with Diabetic, cholesterol, cardiovascular problems, it just enhances the fact that diet and exercise are important for all around good health.

This article summarizes nicely the importance of exercise on brain function and plasticity: http://www.cell.com/trends/neurosciences/abstract/S0166-2236(02)02143-4>. 
This article discusses the relationship between exercise and brain function as a result of increased BDNF secretion. This article shows how the increased levels of BDNF present in the body, stimulates neurogenesis and improves brain resistance to injury, improves learning, and can influence brain plasticity. It seems to me that the more we take care of our bodies now, the lower the risk will of developing neurodegenerative diseases, and not just AD.

Ethan Burns

Surgical options for Parkinson's Patients

We have all heard about the benefits of the cardiac pace maker on patients who have had heart attacks and other related cardiac problems. But what about a pace maker for the brain? That is essentially what a Deep Brain Stimulator (DBS) is. Essentially, patients who undergo this operation get electrodes attached to their brain. The wires to the electrodes are brought down to the patients chest (if they have a cardiac pace maker or are too thin it is typically inserted in their lower midsection), and attached to 1-2 IPGs. Each IPG controls the opposite side of the body. (ie: left ipg controls right motor movements). 

This article basically summarizes the benefits of DBS on PD patients over a 4 year time span:
http://brain.oxfordjournals.org/content/128/10/2240.full.pdf+html

The UPDRS (the PD rating scale, http://www.mdvu.org/library/ratingscales/pd/updrs.pdf) is used to assess the benefits of the DBS on patient off periods, motor movements, and daily living.

As the article stated, there was a noticeable decrease in patient off periods, a great improvement in motor function, and an improvement in daily activities and lifestyle. There are of course side effects. Patients have noted dyskinesia, and decline in speech (slurring) is typically noticeable.

This article was a very interesting read, I highly recommend it.

Ethan Burns

Bee Sting Therapy

Hey all,

After reading the basic science article about treating MS with bee stings, I was curious to find more about the people advocating for such a treatment. When you Google bee therapy for MS there are over 6 million links that pop up. Most of the popular ones are articles from places like Discovery which are good about showing the doubts of the treatment. Some websites however are blogs written by people with MS. These two, http://www.howstuffworks.com/framed.htm?parent=medicine/tests-treatment/bee-sting-therapy.htm&url=http://www.olg.com/beelady and http://www.angelfire.com/va/honeybeeangel/index.html have nothing but praise for the therapy, and the first even has a "products" section where you can buy bee venom.  This has some obvious issues, including practicing medicine without a license and sending bio-material through the mail. I also found a video (http://www.youtube.com/watch?v=Xe2h0vkp1mA&lr=1) that discusses people in Taiwan who use bee stings to treat almost anything. The doctor even claims that 600 bee stings will make you look 5 years younger.

Do you guys think that it is morally wrong to promote a treatment like this? If the authors of the blogs actually have MS and do actually use bee therapy as treatment, then they clearly believe in it's effects, so is there a problem with them encouraging others to try it?

Coconut Oil v.s. Alzheimers

The video given below shows a neonate doctor who has been battling her husband’s severe Alzheimer’s with coconut oil. The doctor says Alzheimer’s seems to be a type of diabetes of the brain.  Glucose is not being taken up by the brain so the cells die. However, there is the alternative fuel of ketones that cells easily accept.  Triglycerides in the coconut oil break down into these.

They use the “clock test” to determine the progress of the patient.  Two weeks after adding coconut oil to his diet the patients clock drawing dramatically improved and kept on improving weeks after that. He started conversing more and became more active.

Oxford has created a highly potent form of ketones yet it is expensive to make and not profitable and therefore not many are interested. I would like to have seen a study done with just the ketones to see if it has the same effects as the coconut oil.

Coconut oil is a natural antibiotic and antiviral. In the article they explain that the oil could even be used for Parkinson's disease, ALS , epilepsy, dementia, even schizophrenia and autism. This sounds like one of those “cure alls” we want to stay away from but it at least has 

http://www.cbn.com/cbnnews/healthscience/2012/January/Coconut-Oil-Touted-as-Alzheimers-Remedy/

Genetics of Alzheimer’s

I’ve done some research in prior classes on the genetics of Alzheimer’s disease so I thought I would share it with everybody.  The “Alzheimer’s Disease and Inflammation: A Review of Cellular and Therapeutic Mechanisms” article briefly mentions the apolipoproteinE (ε4 variant) gene. Although this is the leading risk factor (gene-wise) for Alzheimer’s disease there are other genes associated with AD not included in the article. Other genes include CLU, PICALM, MS4A, CR1, CD33, CD2AP, BIN1, and ABCA7 genes. Check out my ppt on the relevant genes associated with AD in detail!

http://dl.dropbox.com/u/62541740/Genetics%20of%20Alzheimer%27s.pptx

I got this data by using gene search engine websites (description about each listed below). These websites are useful for not only AD but for finding your risk factor for other diseases/disorders such as arthritis, depression, alcoholism, etc!

1. 23andMe: https://www.23andme.com
-Private (for profit) testing company for DNA samples sent in by individuals.
-This site can be used to look up genetic information of various anonymous individuals or a DNA sample.
-It can be used to look up the results at positions along the genome that have been associated with specific diseases and traits to learn the risk of that individual for those diseases and learn the results of traits.

2. Promethease: http://www.snpedia.com/index.php/Promethease

-A site where users can upload their raw data file (usually from 23andme) for further analysis on topics of medical interest. Provides analysis of more genes than 23andme.

-Promethease gives detailed information about SNPs that are related to the development of an array of traits and diseases.

3. Snpedia: http://www.snpedia.com/index.php/SNPedia

-This site is used to investigate human genetics. It includes information about the effects of variations in DNA

-It can be used to get detailed information from specific SNPs mentioned in Promethease (or elsewhere) that includes information about allele frequency in selected populations, chromosome location

4. Spittoon: http://spittoon.23andme.com/
-Spittoon is a blog written by the people of 23andMe. They summarize new literature findings relevant to genes.

Nature Created all of the Locks, Therefore Nature Has all of the Keys

After all this talk recently about conjugate linoleic acid (CLA) in health articles, magazines, and shows like Dr. Oz I decided to do some research and find out if it's a type of supplement I would be interested in trying.  I was very surprised at the plethora of studies and reported health benefits I found!

CLA is a naturally occurring acid found in meat and dairy products known for its anti-cancer and immune modulatory properties. The most promising science around CLA concerns its effect on weight management. Many of these studies vary widely in dosage, subjects, and duration, but have very positive results. A few studies I came across  reported that CLA can up-regulate the tumor suppressor gene PTPRG and has been proven to have anticancer properties. Also, studies on mice and rats show encouraging results in hindering the growth of tumors in mammary, skin, and colon tissues. 

In 2012, and in collaboration with the Division of Gastroenterology and Hepathology at University of North Carolina School of Medicine and the Wake Forest Medical Center, researchers found that Crohn's patients who took supplementary CLA showed noticeable improvement. "In our recent open label study of CLA as a supplement in study subjects with mild to moderate CD there was a marked improvement in disease activity and quality of life in 50% of the subjects. CLA was well tolerated by all of the study subjects. These findings are very encouraging and will need to be verified in a randomized controlled trial," said Professor Kim L. Isaacs, a Professor of Gastroenterology at the University of North Carolina at Chapel Hill.
"The validation of the anti-inflammatory actions of CLA in the gut is in line with our goal because CLA is a natural fatty acid found in milk and ruminant products. The fully integrated bioinformatics, nutrition and immunology experimentation capabilities of NIMML enable the acceleration of translational biomedical research from computational and mathematical modeling into the clinic. CLA is an example of an anti-inflammatory compound in a pipeline of naturally occurring and synthetic compounds (e.g., abscisic acid, eleostearic acid, terephthalanilides) with tremendous therapeutic and prophylactic potential as anti-inflammatories," said Dr. Josep Bassaganya-Riera, a Professor of Immunology, principal investigator of this human clinical trial, and the Director of the NIMML and the Center for Modeling Immunity to Enteric Pathogens.

Wikepedia has many of these research articles listed and further summarizes some of these studies findings. My question to you is, have you ever taken CLA as a supplement, or would it be something you would trust taking as an aid in losing weight or any of it's other claimed health benefits?

http://www.sciencedirect.com/science/article/pii/S0899900711003509

http://www.sciencedaily.com/releases/2012/03/120319194215.htm

http://en.wikipedia.org/wiki/Conjugated_linoleic_acid#cite_note-Amaru-13

Safety and Efficacy of Diacerein for Osteoarthritis

As it turns out, Diacerein (drug name), or Cartidin (Brand name) and ART 50 (trade name Artrodar), is still on the market in many countries, but never was available in the U.S.. As discovered in one of the articles we read last week, Diacerein, a drug used as a therapeutic agent in osteoarthritis, blocks Interleukin-1, as opposed to inhibiting the cylcooxygenase (COX) pathway, interfering with prostaglandin synthesis as NSAIDS do.  After more research, I continued to find that in all of the clinical studies I read about, Diacerein had a reasonable safety profile and efficacy.  It seems as if Diacerein may be more tolerable in patients and may have some advantages compared with the medium to long term use of NSAIDS, which pose a risk of several more severe negative side effects, such as gastrointestinal and cardiovascular events. In France, from 1994 to 2005 and after more than 14 million prescriptions of Diacerein, only nine cases of cardiovascular adverse events were reported (Bukharb Leeb, European Musculoskeletal Review, 2010;5(1):23-29).  Up to 42% of treated patients in clinical trials reported diarrhea or loose stools and darker urine, which most commonly appeared during the first two weeks of treatment, but is found tolerable at the level of the kidney. 18% of these patients withdrew from these side effects and 13% of patients given placebo did as well. What gives?

Although most evidence is derived from the hip joint, Diacerein has consistently shown a positive effect on pain and function in patients with hip and knee OA through majority of clinical trials and metaanalysis. It seems to be a rational therapeutic option in OA patients and in general, plays a key role as a mediator in the inflammatory processes.  It would be nice to see further research and more long term studies on individuals sufferring from OA, not just in the hip or knee joints, but in other areas to fully understand the effects of Diacerein and solidify the hypotheses presented. Perhaps one day it will become FDA approved and favored over NSAIDS in the U.S..

To read more about this and a summary of the many studies done involving patients treated with Diacerein, please check out this very informative review I found:

http://www.touchmusculoskeletal.com/articles/clinical-efficacy-and-safety-diacerein-osteoarthritis-review?page=0,4

Neurodegeneration with Brain Iron Accumulation

Afternoon everyone,

I was looking around the internet at the various types of neurodegenerative diseases that exist and Google did that auto fill-in thing to me and brought up "neurodegeneration with brain iron accumulation."  That's a condition that I have never heard of before so I looked further into it and found this scientific paper on it.

http://www.orpha.net/data/patho/GB/uk-NBIA.pdf

   Neurodegeneration with brain iron accumulation (NBIA) is a genetic disorder that, as its name implies, causes the degeneration of the brain due to a build up of iron.  The disease was originally only discernible post-mortem, and was identified by the rust brown pigmentation that could be observed in parts of the brain.  Fortunately it is now easier to diagnose using an MRI.  The symptoms of the condition include dytonia (which is a neurological movement disorder which results in sustained contraction of muscles, twisting repeditive movements, and abnormal posture), rigidity, and choreoathetosis (which involve irregular writhing and twisting.)   

   The disease is passed down in an autosomal recessive fashion, and though the exact mechanism of the condition is not always the same, around half of those affected by it have a mutation in the PANK2 gene, which results in pantothenate kinase-associated neurodegeneration, which is another name for NBIA.  Individuals are typically symptomatic in the first decade of life, though in some it manifests in the 2nd and 3rd decades.

Unfortunately however is that there is still no effective treatment for the condition itself, aside from typical anti-dystonia treatments to alleviate suffering.  Some of the attempted treatments end up resulting in a systemic iron deficiency before any real change in the brain's iron content is seen, and thus those methods have not proven effective.

Research on this rare condition is ongoing, especially in looking at the other 50% of cases that do not involve the PANK2 gene, to determine what other genes are involved and to look at potential treatments associated with them.

- Jon Patterson

Neurodenerative Diseases - What are they?

Neurodegenerative disease is a term that encompasses not just one, but many different diseases. They are categorized together because they primarily affect the neurons of the central nervous system. In general, these diseases cause degeneration of the CNS that is progressive and incurable. At first, sufferers will begin to lose memory, such as not being able to remember names, but eventually, with the destruction of more neurons they can lose the ability to walk, think clearly, or carry out day to day functions. Many of the diseases have genetic factors, but environment, age, injury, prions, and toxins may also play a role. Most of these diseases have no real treatments, and their occurrence is on the rise. The Institute for Neurodegenerative Diseases in California claims that Alzheimer's will affect half of us before we are 85 years old. Diagnosing a neurodegenerative disease is also difficult, and concrete diagnosis is made postmortem up to 80% of the time. The best way to try and diagnose is to determine the symptoms, which are sometimes similar from disease to disease. Some examples of neurodegenerative diseases are, Alzheimer's, Huntington's, Lewy Body, Amyotrophic lateral sclerosis, Parkinson's, Friedreich's Ataxia, and Multiple Sclerosis.

The diseases in the articles we are reading for this week are very common in the US. According to Harvard's Neuro Discovery Center currently about 5 million Americans suffer from Alzheimer's disease; 1 million from Parkinson's; 400,000 from multiple sclerosis (MS); and 30,000 from amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).

Interestingly, many people claim that sports injuries can be a major determining factor for developing one of these diseases. Articles such as these, http://www.medscape.com/viewarticle/727081 and http://beckersorthopedicandspine.com/sports-medicine/item/1835-research-links-als-like-disease-to-competitive-athletes discuss the link between head injuries and later progression of diseases. Some good evidence for this argument is Muhammad Ali who now suffers from Parkinson's Disease, and Steve Gleason, a former football player who has been diagnosed with ALS. More studies need to be done to not only find the cause of the diseases but to see what kind of risk factors we as a population are commonly exposing ourselves to.

Nutrition & Neurodegenerative Diseases

As you guys have figured out this far into the semester, nutrition plays a huge role in regulating inflammation. It's certainly no different when it comes to neurodegenerative diseases.

http://www.jneurosci.org/content/29/41/12795.full.pdf+html
This article from the Journal of Neuroscience outlined the benefits of different food categories on neurodegeneration. Phytochemicals, such as antioxidants, are substances in plants that go beyond providing calories and vitamins/minerals; they have protective effects against disease, even in the plants from which they come. The study first looks at the effects of berry polyphenols on aged mice and found that those treated with blueberry and strawberry extracts experienced improved working memory along with other benefits from each extract individually, such as improved balance, cognition and coordination. Blueberry extracts may be protective against stress signaling to inhibit production of nitric oxide and inflammatory markers. Polyunsaturated fatty acids from walnuts and fish are important for maintaining membranes on the neurons, synapses and signal pathways responsible for stability in the hippocampus, cerebellum and cortex. Curcuminoids (curcumin), the yellow substance in tumeric, may also be protective by inhibiting proinflammatory cytokines and stimulating clearance of amyloid plaques. There has also been significant research that calorie restriction has a protective effect against inflammation since the act of eating, itself, has an inflammatory effect on the body.

One looming problem in the field of nutrition is determining the correct dosage of phytochemicals that is bioavailable (able to be absorbed by the body) and protective. As our food has multiple compounds within it that interact with one another, it is difficult, if not impossible, to isolate any single compound as being preventive against disease. There have been many cases (such as with Vitamin E), where the food sources have been seen as protective but the supplement form can lead to increased cancer risk. In addition, cancer takes years to develop so by the time supplements are recommended, they may have proliferative effects rather than protective (Crider, 2011).

It is my personal opinion as a student of nutrition that we should get our vitamins/minerals/phytochemicals from whole foods and not from supplements. We are at the advantage that we have years to protect our bodies against cancer & other preventative diseases- why not start now? What are your opinions??

High Intensity training as Rheumatoid Arthritis treatment.

Hey you guys,
I found an interesting article. We were talking about this past week of Osteoarthritis and how it might be inevitable to someone no matter how early or how many preventative causes we take to stop it. In this article, we see Rheumatoid arthritis and comparing regular physical therapy called "UC (usual care)" to High intensity training as a therapy termed RAPIT (Rheumatoid arthritis patients in training). Basically in this article A study was done on over 300 people, and were either given physical therapy or High intensity training to help remedy their RA. Overall the study found that patients with High intensity training had greater aerobic fitness and muscle strength. This was a good study for me to see because usually studies that have to do with actual exercise are only seen in Osteoarthritis patients and not RA patients with arthritis in their synovial capsules between their joints.

A major problem I have with this study though is that the study doesn't clearly define or really give any detail on what the physical therapy that the patients, who are not participating in RAPIT, go through. The only information that I can find on the paper is information saying the patients went through deemed "normal" physical therapy. This I didn't like, because unlike the UC group, the RAPIT group was clearly defined in what kind of physical activity day they are likely to go through.

What do you guys think about this study?
-Do you agree with me that there in a major problem in the absence of defining the UC (usual care) group?
-  Is there any other major problems that you find with the study? such as age? (the range was from age 20-70)
Let me know what you think please.

The links are below:

http://onlinelibrary.wiley.com/doi/10.1002/art.11216/pdf

http://onlinelibrary.wiley.com/doi/10.1002/art.11216/full

-Xavier V.

Rating Scales for ALS and PD

I thought that it would be interesting to look at how Doctors rate symptoms in different neurodegenerative disorders, so I found two different rating scales: One for ALS, and one for PD.

ALS rating scale:
http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=3&ved=0CDYQFjAC&url=http%3A%2F%2Fwww.cebp.nl%2Fvault_public%2Ffilesystem%2F%3FID%3D1218&ei=DeaBT4rNF6KjiQLBibm7Aw&usg=AFQjCNGirIE0JEWMRHkEotymSLu6nsVEZg

-note that this opens as a word document, not as a ling to a website when you copy and paste it into your browser.

PD rating scale:
http://www.mdvu.org/library/ratingscales/pd/updrs.pdf

-I really like these scales. I have had the chance to only use the ALS scale once, but I have used the PD scale many times. It is organized in a very concise way that assesses the patient's mentality, how their daily lives have been effected, if there are any side effects of medication (or deep brain stimulator, if applicable), and a motor exam that shows the severity of symptoms.

I also included one other link, called the Montreal Cognitive Assessment (MOCA). This is used for many patients with cognitive disorders such as dementia.
link: http://www.mocatest.org/pdf_files/test/MoCA-Test-English_7_1.pdf

if you look at thes test, you can see for us it is pretty easy and straight forward. But for patients suffering from many neurodegenerative disorders have a lof of trouble even doing the first two problems (although I must admit, cubes can be hard to draw).

Ethan Burns

Osteoarthritis and Chondrocytes

Hey guys,

I found just a quick blurb on a possible explanation of how chondrocytes may contribute to the onset of osteoarthritis. It appears that the chondrocytes will eventually begin to proflirate and spread. Their gene expressions possily upregualte the MMPs and other things that possibly degrade the cartilage within oue bodies. It explains how this upregulates bone-specific collagen type I and X which can cuase calcification and hardeneing of the cartliage. It also states how certain expressed genes are in part of the growth plate which might be why there is such an onset of osteoarthritis due to chondrocytes.

I thought it was in an interesting short blurb basically explaining in short and brief what a couple of the articles we read suggested.

http://www.medscape.com/viewarticle/579393_9

This link also guides to morth in depth discussion and the other parts to the article and are kind of fascinating!

I hope you all enjoyed arthitis!

Michele

Universal Arthritis Scoring system you ask?

During our arthritis discussion we questioned the arthritis scoring system because it seems to be arbitrary. I wanted to look into this more and see if there was a universal radiographic or histology arthritis scoring system for RA.

As seen in “IL-1ab Blockade Prevent Cartilage and Bone Destruction in Murine Type II CIA, Whereas TNF-a Blockade Only Ameliorate Joint Inflammation” article, they used histology and radiography to analyze joint destruction, inflammation, bone erosion, and cartilage destruction. I decided to go off of this to find relevant information and I found 4 main methods of radiographically scoring RA http://ard.highwire.org/content/60/9/817.full  (and nothing for Histology scoring for RA!) which include: the Steinbrocker Method, Kellgren Method, Sharp method, and Larsen Method.  Unfortunately these methods only looked into bone erosion and joint space narrowing so scoring for other issues such as joint destruction, cartilage destruction and inflammation seem to be dependent on the study (for more information on the different methods check out the link). In my opinion, I don’t find this very reliable and is  surprising to me since there are so many studies on arthritis and radiography and histology are very common ways of analyzing it.

Even more, this article did not resemble any of the 4 main methods of radiographically scoring RA. Hmm.. So my question to you is, should there be a universally accepted technique in analyzing arthritis histologically or radiography or should it rather be dependent on the type of study at hand? Are there any problems/restriction that may come about if we were to enforce a universal method of scoring? Or are there any benefits of not have a universal scoring system at all?

More info on scoring: 

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDQQFjAB&url=http%3A%2F%2Fwww.nyuhjdbulletin.org%2FResource%2FDocuments%2FCRMC2%2F9%2520-%2520Sokka.ppt&ei=N758T9ftMsKhiQLWtYSQCg&usg=AFQjCNGy0gkfxSmJmwZF1a52NJ8xXvBc0Q