Range of brain diseases could be treated by single drug

By James Gallagher Health and science reporter, BBC News

Link:  http://www.bbc.co.uk/news/health-17952797

The author of this article sites a new study, recently published in Nature (abstract link below), which details a possible new therapy for neurodegenerative diseases.  If successful this drug could target numerous diseases including Parkinson’s, Alzheimer’s, Huntington’s, and prion diseases, such as the human form of mad cow disease.  This study utilized a mouse model of prion disease.  It is thought that the contributing factors to these diseases are accumulations of miss folded proteins.  They showed that as misfolded protein levels rise in the brain, cells respond by trying to shut down the production of all new proteins through phosphorylation of the α-subunit of eukaryotic translation initiation factor, eIF2.  Increased eIF2α-P levels are seen in neurodegenerative diseased patients.  It is theorized that cell death might result because this arm of protein synthesis is shut down leaving cells unable to rebuild and replenish themselves.  There data showed that increasing eIF2α-P levels, exacerbating neurotoxicity and significantly reducing survival in prion-diseased mice.  While reducing eIF2α-P levels decreased neuronal death and increased survivability of the mice.  Their results suggest that manipulation of common pathways such as translational control, rather than disease-specific approaches, may lead to new therapies preventing synaptic failure and neuronal loss across the spectrum of these disorders.

Certainly interesting work...  I would like to see more data on the longevity of these studies.  I wonder if other side effects would result due excessive protein buildup.  In numerous papers we have read they mention the inflammatory response due to excessive protein deposits.  Would this response be worsened, resulting in disease progression, if protein synthesis is not curbed?  I wonder if a combination of therapies could be utilized to lessen side effects while improving disease prognosis?

Nature abstract:  http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11058.html

The magic of Botox

Botox has come a long way since starting as a treatment for lazy eye!!!

From treatments to reduce blepharospasm, torticollis, and facial spasms, to the not so neurological specific use of revitalizing the face (if you are one of those stars that can afford the $500/mL injections), botox has come a long way in proving its usefulness in a wide range of clinical environments.

More recently discovered is its possible function in the field of urology, more specifically, reducing bladder outlet obstruction (obstructive and irritating urination problems).

Article Link: http://www.biomedcentral.com/1471-2490/6/12

The research in this article found that botulinum toxin type A (commonly called botox), when injected into the bladder of male humans and dogs, induced prostate apoptosis in dogs, and reduced bladder outlet obstruction in males. This treatment has proven beneficial for the aging population, especially those with neurodegenerative diseases which aggravate the effects of bladder problems like Parkinson's disease. Botox typically doesn't last more than 3 months. It is different in everyone, as it depends on the sensitivity of the anchoring proteins in their presynaptic cleft that bind the vesicle to the wall. Some people may need a higher quantity injected to feel an effect, and some may be completely immune to the type a strain.

It would be interesting to conduct a study that looks at the effects of some of the other strains of neurotoxins, like dysport, myobloc, and xeomin, and see if they have similar results (the different strains are either more purified or act on different anchoring proteins).

Alzheimer’s Disease Basic Scientific Article

Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer’s disease.

Alzheimer’s disease (AD) is characterized by abnormal senile plaques and neurofibrillary tangle formations.  Amyloid-β peptide (AB) and precursor protein (AβPP) are the major components of these senile plaques.  Aβ is thought to be a major contributor to the neurodegenerative process, acting either through neurotoxic mechanisms or local inflammatory processes.  Interestingly one of the early hallmarks of AD is abnormal cerebral vasculature.  Neurovascular damage can allow fibrinogen access to the CNS.  Fibrinogen, classically known for its role in the clotting cascade, cannot normally cross the BBB.  Fibrin is found in the brains of AD patients, but the pathological significance is unknown.  Fibrin accumulation can be reduced genetically or pharmalogically. 

The aim of the experiment is to measure BBB permeability and fibrin deposition in three mouse models of AD.  Their results demonstrate BBB damage and the presence of fibrin in the brain of AD mice.  Furthermore the tPA/plasmin system, which likely aids in the clearance of Aβ, is down regulated in AD in accord with reductions in other naturally occurring Aβ-degrading proteases.  Also modulation of fibrin levels affects the pathology of AD mice, reducing fibrinolysis, thereby increases fibrin deposits, worsening the pathology, whereas fibrinogen depletion attenuates microgliosis and neurovascular damage.  Decreased clearance of fibrin is also thought to contribute to the progression of Aβ pathology.  The initial insult to the microvasculature likely arises from increased Aβ levels.  Fibrinogen binding elicits activation of NF-KB, caused increased expression of cytokine genes.  Thus fibrin may be an upstream effector of neuroinflammation .  Also fibrin-induced microgliosis could be toxic to endothelial cells.  Fibrin along with the mechanisms involved in its clearance, may present novel therapeutic targets for slowing the progression of AD.

The author’s utilized pharmacological methods to examine fibrin’s role, namely from platelets, in AD mouse models.  The aim was to reduce protein sources, which are linked to senile plaques, in order to prevent or lessen AD.  The data does suggest that this therapy is an effective way of modulating AD in mouse models.  However if this line of therapy was employed in human subjects significant side effects could result.  Humans are far more sensitive to reductions in platelet levels compared to mice.  If human platelet levels were reduced to those of the mice in these studies minor injuries could become life-threatening situations.

Source:  Justin Paul, Sidney Strickland, and Jerry P. Melchor:  Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer ’ s disease, Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065.

Love Drug?

Hey you guys I was just getting online today and I found this article on my msn.com homepage. I thought it would just be interesting to post on here even though its not really an inflammation issue. Its for a thing called the "love pill." Basically in this article it speaks of a new type of pill that scientists want to develop to hopefully prescribe to people in marriages who just aren't happy. In their paper entitled Neuroenhancement of Love and Marriage: The Chemicals Between Us, they speak of this pill to salvage failing marriages, and in today's world of constant divorce, i fell like if the broad lay community heard about this and believed it, it could have a huge selling as the top drug on the market. In this article they speak of the ingredients that this drug will have such as:
1) Pheromones
2) Testosterone
3) Oxytocin and Vasopressin, what they call "bonding chemicals"
4) Entactogens- "a drug found in MDMA pills like ecstasy"


Although this product is not yet in development, I found it interesting to note that I believe, if it works will cause some people to be in a relationship that otherwise they wouldn't be in. 


heres the link to the article on msn


http://living.msn.com/love-relationships/the-heart-beat-blog-post?post=71cbc378-6d27-4219-a464-df8e7645289a


and here is the original paper itself


Neuroenhancement of Love and Marriage: The Chemicals Between Us

Omega-3 Fatty Acids: what they do, and current research

Having gone through the anti-inflammatory articles we discussed on turmeric, it seems that many are looking to curcumin in hopes of providing a strong defense against chronic-inflammation diseases. Then after doing some thinking, I remembered that curcumin isn't the only anti-inflammatory that many people are pushing to consume because they believe it to be the magic cure all. Omega-3 fatty acids are just as equally pushed for their ability to reduce inflammation as well as assist in heart disease and stroke recovery, but what do we really know about Omega-3 fatty acids? Well, I was curious so I went and did some research on them and found some interesting information.

As it turns out, Omega-3 fatty acids are comprised of three different Essential Fatty Acids (EFA), that our bodies need to properly function. The three EFAs that make up Omega-3 fatty acids are decosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and alpha-linolenic acid (ALA). According to my sources these Omega-3 fatty acids are found predominately in fish-oil and certain plant and nut oils; DHA and EPA are found predominately in fish oil, whereas ALA is found predominately in nut and vegetable oils. Moreover each plays a unique role in what our bodies use them for; DHA for example is needed to maintain proper brain function as an adult, and is needed for the development of the nervous system and visual abilities during the first six months of life. EPA has been found to help lower risk of heart disease, and has been shown to have positive protective affects on coronary heart disease, high triglycerides, high blood pressure and inflammation. Finally, ALA is the interesting one, as its main contribution seems to be that, it can be converted into both EPA and DHA in our bodies.

Now, while reading about this is good I'm the kind of person who likes more detail, its cool to know that they can do these things but I also like knowing how they do these things. So I searched the boundless Internet in hopes of finding any research that had looked into this, and I did find scientific research articles looking at the mechanisms of each fatty acid. Unfortunately, I could only obtain the abstracts as the articles are owned by PubMed and they wouldn't let me obtain the full reports. However, just reading the abstracts gave me a better understanding of the research that was being undertaken in order to better understand the role each Omega-3 fatty acid plays in helping us to remain healthy.

The links below will take you to the places where I have obtained my information, links 2-4 are the same website, and it's defiantly more of an overview of information website than it is a detailed information website, but nonetheless contains useful information regarding the Omega-3 fatty acids. Links 5-7 are the research article abstracts I've found on each Omega-3 fatty acid, and while they are not the full articles they do provide an excellent summary of the contents of each paper. Also if someone who is familiar with PubMed could tell me how to access the full articles, I would be more than happy to edit this to take you to the full articles because the abstracts make me want to see the full thing. Finally, link 1 provides a nice overview of what the Omega-3 fatty acids are in general. Enjoy and leave any comments below.

 
http://www.mayoclinic.com/health/fish-oil/NS_patient-fishoil
http://www.umm.edu/altmed/articles/docosahexaenoic-acid-000300.htm
http://www.umm.edu/altmed/articles/eicosapentaenoic-acid-000301.htm
http://www.umm.edu/altmed/articles/alpha-linolenic-000284.htm
http://www.ncbi.nlm.nih.gov/pubmed/11724467
http://www.ncbi.nlm.nih.gov/pubmed/15881480
http://www.ncbi.nlm.nih.gov/pubmed/19641487

Neuro Review Article of Alzheimer’s disease

ALZHEIMER’S DISEASE AND INFLAMMATION:  A REVIEW OF CELLULAR AND THERAPEUTIC MECHANISMS

Alzheimer’s disease is the fourth leading cause of death in persons over the age of 65.  It is incurable and progressive and affects millions of people across the world.  Alzheimer’s disease (AD) is the most common neurodegenerative disease that causes dementia.  The three major pathological hallmarks of this disease are characterized as senile plaques, neurofibrillary tangles, and inflammation.  Senile plaques consist primarily of protein deposits, namely b-amyloid fragments.  These amyloid fragments seem to mediate inflammatory mechanisms by activating microglial cells via the complement pathway in a similar fashion to immunoglobulins.  Platelets are a major source of amyloid fragments thus therapies are proposed to curve platelet numbers and thus a source of protein fragments.  Also the use of NSAIDS to reduce the inflammatory microglial cell activation is discussed.

Inflammation of neuronal tissue can both be beneficial and detrimental depending on circumstances.  For example in brain injury the inflammatory response can:  aid in clearing out dead cells, debris, inhibit neuro toxic cytokines, and promote growth factors needed for recovery.  Conversely improper or chronic inflammation can cause severe damage and widespread death of neuronal cells worsening prognosis.  Possible drug interventions to curve these deleterious effects are proposed.  Evidence from RA patients who consume anti-inflammatory medications regularly does seem to show slowing of the progression of AD.  In conclusion the author’s call for future studies aimed at targeting the inflammatory process via NSAIDS and anti-platelet therapies. 

Source:  Glenda Halliday,* Stephen R Robinson,‡ Claire Shepherd* and Jillian Kril.  BRIEF REVIEW:  ALZHEIMER’S DISEASE AND INFLAMMATION: A REVIEW OF CELLULAR AND THERAPEUTIC MECHANISMS, Clinical and Experimental Pharmacology and Physiology (2000) 27, 1–8.

Being physically active may protect the brain from Alzheimer disease

This article was published in the April 2012 edition of Neurology.  The author’s study correlates the link between high levels of activity with reduced rates of Alzheimer’s disease.  716 subjects in this trial wore wrist monitors called actigraphies.  These monitors broadly assess the “activity” levels of these individuals.  Cognitive test were administered annually over the course of four years.  During this trial 71 patients developed Alzheimer’s disease.  It was concluded that the least physically active group was twice as likely to develop Alzheimer’s when compared to the most active.  In addition, the most vigorously active group was three times less likely to develop the disease. 

Although actigraphy cannot provide the exact physical activities subjects undertook it can provide a broad picture of overall activity levels.  For instance the devices were unable to determine whether subjects were playing cards or sprinting in a race.  The authors contend that this doesn’t really matter because they recorded total activity levels.  It is also stated that what is truly important is simply living a more active lifestyle and being less sedentary.  As long as the subjects engaged themselves in some type of activity the risk of developing Alzheimer’s disease was decreased.            

This brings up an interesting point.  Is it realty the vigor of physical activity that decreases risk?  Or is it rather some combination of increased mental stimulation and physical activity due to active lifestyles that decreases risk? 

Link to lay article http://www.foxnews.com/health/2012/04/18/active-lifestyle-cuts-risk-alzheimers-at-any-age-study-finds/

Link to actual article http://zp9vv3zm2k.ssscom.ezproxy2.library.arizona.edu/?url_ver=Z39.88-2004&rfr_id=info%3Asid%2Funiversityofarizona.worldcat.org%3Aworldcat&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&req_dat=%3Csessionid%3E&rfe_dat=%3Caccessionnumber%3E7893

How the manipulation of molecules in the heart may treat obesity!

During my weekly medGadget peruse I found this interesting article about a study just recently published in Cell.  
http://medgadget.com/2012/04/in-study-altering-heart-molecules-protects-against-obesity.html

In short, researchers at UT Southwestern found that a regulatory molecule in the heart, in this case mi-RNA-208a, that actually has an effect on the body's metabolism by effecting MED13 (mediator complex subunit 13), which is known to control transcription of thyroid hormone. micoRNA-208 has been shown to negatively regulate MED13 and in this particular study researchers show that cardiac-specific over-expression of MED13 OR pharmacologic inhibition of miRNA-208a provides mice with a resistance to high-fat diet induced obesity.

• I'll back track for a sec to explain what miRNAs  (micro RNAs) are: mi-RNA are short, single stranded RNA molecules usually around 20-25 nucleotides in length and are known to regulate gene expression.  Unlike mRNA, miRNAs don't actually encode for proteins but function by preventing translation of mRNA. So, in the case of miRNA-208a, we see prevention of MED13 translation.

The group also found that mice with a MED13 gene deletion, specific to the cardiomyocytes,  are prone to metabolic syndrome.  The hope is that in the future, miRNA-208a and MED13 can be targeted to help control metabolic disorders.

So, we've all learned that obesity, type 2 diabetes, and stroke are all inflammatory disorders; my  big question now is how does regulation of MED13 affect inflammation in the body??
Will we see prevention of chronic inflammation along with prevention of metabolic issues?
What would happen if an obese person with chronic inflammation was treated with miRNA-208a inhibition? -Would we see a reduction in that person's inflammation also??
If we do see a reduction in inflammation, would this treatment help in other inflammatory diseases??

There's lots more interesting research to be done!!

If you'd like to take a look at the journal article, search "A cardiac MicroRNA Governs Systemic Energy Homeostatis by Regulation of MED13" CE Grueter

Good control over blood glucose levels may lessen post-stroke damage?

There has been debate over the connection between blood glucose levels and severity of stroke, which is no surprise given the vast web of interconnecting inflammation in the body.  Dr. Bruno, a stroke specialist at the Medical College of Georgia, is investigating the use of insulin injections to help alleviate post-stroke damage.  Dr Bruno, who is also a clinical PI for the National Institute of Neurological Disorders and Stroke-funded study, believes that, upon admittance to the emergency room, every stroke patient should be given an insulin injection.  Generally, simple finger-prick tests are administered to check for diabetes anyway, so he believes that an insulin injection should be a standard as well, whether or not the patient is diabetic.  His rationale for this is that generally, stoke victims suffer more damage when blood glucose levels are high, so a quick dose of insulin should help lower glucose levels and therefore minimize damage.  In addition, he explains that low blood glucose levels can mimic stroke symptoms, so an insulin injection may lead to less false-positives. 

Does this theory sound promising?  Possibly.  Nearly 1400 physicians in the U.S. are claiming to subscribe to this easy treatments, but the exact method for success is not clear.  It is believed that stroke triggers the release of stress hormones, and they may interfere with the ability of cells to uptake glucose, leading to higher levels in blood.  So what causes the damage?  Dr. Bruno hypothesizes that free radicals released during stroke amplify the damage.  He is currently working a this trial, termed the SHINE Trial, in which stroke patients either receive insulin injections or, in tougher cases, IV insulin for three days.  Three months later, the patients' health is assessed. 

I thought this concept is interesting, and not too far-fetched.  Insulin injection, at proper doses, should be safe, and it makes sense that you would see elevated blood glucose levels post-stroke due to wide-spread effects of inflammation.  However, the article did not clarify how control over glucose levels would affect stroke damage, merely that there appears to be a connection.  This news article also did not link a scientific paper or study, possibly because this group has not yet published on the topic. So the bottom line is:  are elevated glucose levels partially responsible for more severe damage, or is this just an association?  The answer to this question could provide the link necessary to truly treat strokes more effectively.

Study seeks to improve stroke outcomes by optimizing blood glucose control

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/