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.