Do cytokines play a role in cardiovascular disease?

     Many people can guess that there is a high probability of cardiovascular disease and diabetes. The article we discussed this past week was, "Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease". The three main cytokines discussed were IL-6, TNF-alpha, and IL-1beta. IL-6 stimulates C-reactive protein release from the liver, causes insulin resistance and causes to the proinflammatory state. TNF-alpha impairs insulin signaling and causes insulin resistance in individuals. IL-1beta is an important mediator of the inflammatory response, and is involved in cell proliferation, differentiation and apoptosis. 

     The three cytokines were experimented on in 4 types of individuals; women with no cardiovascular disease(CV) and no diabetes(D), women with CV and no D, women with no CV and D, women with CV and D. The various experiments showed the levels of the three cytokine levels in each individual. The main point of the idea was that the levels of the cytokines were to have a multiplying effect in individuals who have both CV and D. One important point that we discussed in class was that although the graphs in this article are displayed as though there is a multiplying effect, the writers have just shown it in a way although the amounts are really not too much out of the norm. 

     In one of my statistics classes, the professor always tells us that there is always a way to manipulate the data and our job as statisticians is not to fool the viewers with these false truths. I always feel like a superhero, in how I need to use my power for good to save the innocent. 

     On another note, IL-6 and TNF-alpha both showed the "multiplying effect" but the IL-1beta did not display the same effect in their results of experimentation. One thing I had mentioned in class was the fact there was high range of age differences between the individuals in each category which there people may develop diseases if they were at the same age as the others as well. The fact of the age difference was one which struck me as most odd of why they chose to choose those individuals rather than comparing more similar individuals with the various disease states.

"Curcumin Extract for Prevention of Type 2 Diabetes"

Since we look at a lot of studies done in mice models, here is one done in humans!

The purpose of this study was to determine if curcumin can delay type II diabetes in adults under the age of 35.  240 test subjects were given a curcumin supplement or a placebo for 9 months.  They took 3 curcumin capsules per day, each containing 250mg of Curcumin (in addition to a heather lifestyle).  After 9 months, none of the people in the curcumin group were diagnosed with Type II diabetes. (While some in the control group were).  The curcumin group also have increase in β-cell function, adiponectin and anti-inflammatory cytokines.  They also found no adverse effects from the curcumin supplement amount.

The subjects were given lifestyle modifications for them to have a healthier lifestyle.  I thought this helps show, that there is not a "cure all" method.  There is still much responsibility of the individual to eliminate as many risk factors as possible if they really want to feel better.  This study shows that you don't see overall significant result until after the 6 month period.  Those who are looking for the quick fix, will unlikely see beneficial long term results.

In this study you can really see all the variables you have to take into account when doing a study with humans! Such as medications, age, and even the diagnosis method of pre-diabetes or type II diabetes.

Website: http://care.diabetesjournals.org/content/early/2012/07/02/dc12-0116

Full article: http://care.diabetesjournals.org/content/early/2012/07/02/dc12-0116.full.pdf+html

What!?!? Weight Gain = Longer life

Give this article a spin!

http://www.huffingtonpost.com/2013/09/20/extra-weight-live-longer_n_3962226.html

I find it interesting that the idea of a diachronic viewpoint regarding an individual's weight is a better indication of one's health. From a scientific standpoint it almost makes too much sense. Two examples come to mind - Blood pressure (BP) and Hb A1c (hemoglobin A1c or glycated hemoglobin). 

It seems to be common knowledge that the measure of BP is not a static measurement. A patient can have really high blood pressure when visiting their PCP, while their past history indicates normal BP readings. Does the high BP mean the patient now has atherosclerosis or cardiovascular disease or other issues associated with hypertension? 

Hb A1c is a blood test used to determine a patient's (typically with diabetes) average plasma glucose concentration. However a patient may have a positive test upwards of 9-10% when historically they are well controlled at 3-5%. Again does that mean this patient's diabetes is spiraling out of control because of this one test?

These questions may seem a little absurd, but using such questions in the context of weight gain is an interesting idea.

I do like how the author of this article slyly throws in the caveat of, "results applied only to those over 50". I feel such a statement should be incorporated in the title. Furthermore, they do not condone obesity as a positive, nor do they suggest rapid weight gain after 50 is a good thing, but instead gradual gains or being slightly overweight could be beneficial. Overall I liked the article - after much dissection. I suppose the message is moderation is a good thing, even if it leads to being slightly overweight - Is that a good message to send, given our current situation/epidemic...?

Inflammation Directly Responsible for Most Common Form of Stroke

It is well-known that strokes are deemed by many as the silent killer (Web MD) because they happen often with very little warning sign; sometimes symptoms do not appear until just minutes before a stroke event.  That being said, the symptoms are very well-documented in the wonderful introduction post by Negeen.  Most startling is the fact that a person suffers of a stroke every 53 seconds in the United States alone; approximately half a million people are afflicted each year.  Of those, Ischemic strokes account for about 75% of all events while hemorrhagic strokes account for the other quarter...  So why is it that Ischemic events are so much more common?

Now we all know that the University of Arizona is an awesome place so I'd like to point out an extremely well-written article by one of our own, Dr. Bruce M. Coull, in which he embarks on the answer to that question above.  Here is a link to his published text:  http://stroke.ahajournals.org/content/38/2/631.full.pdf  

From Negeen's intro, we know that the main event associated with this type of stroke is the formation of a thrombus, which either directly blocks blood flow to the brain, or breaks off from somewhere else in the body (embolus) so as to travel to the brain and disrupt its blood and oxygen supply.  Dr. Coull adds that "a panalopy of acute and chronic infections as well as many exogenous and intrinsic sources of inflammation is associated with an increased risk for ischemic stroke".  He also points out that "atherosclerosis producing focal carotid stenosis localized to the carotid bulb and proximal internal carotid artery is a principal cause of atheroembolic ischemic stroke in North America."  Atherosclerotic lesions can form over time and are mostly "characterized by chronic inflammation within the vessel wall in a response to the deposition of oxidized LDL cholesterol components."  This information is extremely critical to understanding the slow development of these conditions that eventually lead to an ischemic stroke event.

What's most interesting is that we can bring it back to everything recently applied by our obesity specialists.  The bottom line is that usually people who are obese have extremely high cholesterol, which is quite essential to setting the table for stroke conditions in the brain.  Diabesity, along with high cholesterol, are very correlative to chronic inflammation in the body, which is hypothesized as one of the main precursors to Ischemic strokes.  I wonder just how many strokes we could eliminate in the USA if we took a long term stand against the absolute biggest health issues facing our country today- diabesity, hypertension, and chronic inflammation.  These are the conditions that make Ischemic strokes much more prevalent than Hemorrhagic strokes. 

Work Referenced:

-Negeen's intro:  http://www.medicalnewstoday.com/articles/7624.php

-Web MD:  http://www.webmd.com/healthy-aging/features/stroke-silent-killer

-Dr. Bruce M. Coull's "Inflammation and Stroke":  http://stroke.ahajournals.org/content/38/2/631.full.pdf     

The Relationship Between Persistantly High Blood Sugar And Kidney Failure

The purpose of this study was to examine individuals with long standing type II diabetes with kidney failure which is known as diabetic nephropathy.  The study compared people with diabetic nephropathy to those with long standing controlled type II diabetes without, nephropathy as well as healthy individuals.  The aim of the study was to determine if those with diabetic nephropathy had different levels of circulating inflammatory chemicals, also known as proinflammatory cytokines, compared to those without nephropathy.  The study specifically looked at antioxidant levels, BMI, proinflammatory cytokine levels.  The study consisted of two hundred people.  The subject fasted for eight hours and then had their blood drawn and analyzed. 

The study found that those with diabetic nephropathy had higher levels of proinflammatory cytokines and decreased levels of certain antioxidants in their blood.  Those with diabetic nephropathy also had lower BMI and hemoglobin when compared to the other groups.  They concluded that persistently high blood sugar levels can lead to inflammation which to damage to the kidneys.

Singh, N., Deepak , K., & Nivedita , S. (2012). Type-2 diabetic nephropathy: A proinflammatory cytokine associated disease due to hyperglycemia induced oxidative stress. Manuscript submitted for publication, Department of Biochemistr y , G. R. M edical College, Gw alior M.P, , Available from ScopeMed. (JARBS. 2012; 4(2): 137-140)Retrieved from http://www.scopemed.org/?mno=30136

Stroke

Hi Everyone,
My fellow group members and I will be presenting our topic, Stroke, this Monday (9/30).  Below I have posted a link to a website the gives a general overview on what stroke is.  It explains the main types of strokes, who is at risk, causes, symptoms, etc.  I hope this background information will be helpful and useful to you while you are reading the articles Dr. Cohen has posted. :)

Crosta, Peter. "What Is a Stroke? What Causes a Stroke?" Medical News Today. MediLexicon International, 25 May 2014. Web. 27 Sept. 2013. <http://www.medicalnewstoday.com/articles/7624.php>.

Can cocoa powder reduce obesity related inflammation?

Penn State researches looked at the effect of cocoa powder on controlling inflammation related to obesity. 

Mice were fed a high fat diet with10 tablespoons of cocoa powder, over the course of 10 weeks.  The control group were mice fed a high fat diet with no cocoa powder.  There results were a decrease in inflammation markers, as well as fatty liver disease.  One result was a 27% lower levels of plasma insulin levels in cocoa fed mice than the control group.  Liver triglycerides were also decreased by about 32%.  High levels of insulin is an indicator of diabetes, while high liver triglycerides is an indicator of fatty liver diseases.  There was not much effect on the weight loss of the mice, however cocoa fed mice did have a lower rate of weight gain.

The researches have two reasons to explain the effects.  The cocoa disrupts precursors that activate the inflammatory effects of the immune system.  Or the cocoa aids in the gut-barrier function to prevent unwanted endotoxins from entering the blood stream.  However, how is not known.

Cocoa has a much lower fat and sugar content, and higher fiber level than chocolate. It also contains polyphenolic compounds (antioxidants).  Some possible effects of consuming polyphenols is reduction in inflammation, and down-regulation of oxidative LDL’s (“bad” cholesterol). 

Penn State (2013, June 12). Cocoa may help fight obesity-related inflammation. Penn State News. Retrieved September 20, 2013, from http://news.psu.edu/story/279134/2013/06/12/research/cocoa-may-help-fight-obesity-related-inflammation

Cure Diabetes With Weight Loss?

Little is known of the long-term effects associated with a resolution of T2D (Type II Diabetes - formerly known as Noninsulin-Dependent Diabetes Mellitus or NIDDM) in patients who've undergone Gastric-Bypass Surgery and other weight loss surgeries. More and more research is surfacing in both academic circles as well as local, public news sources about the many immediate benefits of metabolic and bariatric surgeries. One such benefit is the remission of T2D among the very obese (those with a BMI>40) who have had the disease for more than one year since initial diagnosis. Dr. Walter Pories, considered a pioneer in such research, first published findings of his research in 1992, suggesting that due to [Greenville] gastric bypass surgery 107 of his 137 obese T2D patients went into clinical remission (1). Fast-forward 20 years and there are similar findings among those in both diabetes and bariatric research. Unfortunately however, little is still known as to why this happens. The ASMBS (American Society for Metabolic and Bariatric Surgery) states, "Many patients with [T2D] experience complete remission within days of metabolic surgery, long before significant weight comes off" (2). Because of such observations and results after surgery it is a common misconception that only a decrease in weight is a formidable way to combat and even "cure" T2D. Although weight loss allows for T2D to be more manageable, the ADA (American Diabetes Assoc.) as well as Dr. Blandine Laferrere feel a more complex process is at work (3).

Findings from other sources conclude the significant decrease in typical blood tests (HgbA1C, fasting plasma glucose and serum insulin) associated with T2D, post gastric bypass surgery. It is well documented that a change in ones lifestyle to include a more nutritious diet, regular exercise, and a less sedentary lifestyle can result in a decrease in weight, thus resulting in better health. Paul O'Brien et.al. suggest the use of Lap-Band surgery can assist patients to achieve the goals of a healthy life. Furthermore, O'Brien's findings suggest the weight loss can improve several aspects of one's health to include diabetes, asthma, dyslipidemia, hypertension, sleep, and reflux (4). More research offers explanations to how gastric bypass surgery, which is obviously associated with a marked weight loss, leads to a reduction in insulin resistance and indices of chronic inflammation (5).

Despite all these remarkable findings, the ADA (American Diabetes Association) stands by the gold standard of T2D prevention to being a healthy diet with moderate exercise. Therefore, do such findings from surgery "curing" diabetes offer a misleading solution to T2D? In a sense, is it possible that these findings will lead the general public to continue to have a "westernized" sedentary lifestyle? Thus leading to the conclusion or mindset of, "I can always have a quick fix surgery if my obesity and diabetes gets too out of control."Cures, however the form, are a wonderful thing but at what point does preventative medicine take a backseat to the quick fix? A quick fix where there is little known of the long-term effects.

1.    Pories W, MacDonald K, et.al. (1992) Is Type II Diabetes Mellitus (NIDDM) a Surgical Disease? Annals of Surgery
2.    http://asmbs.org/benefits-of-bariatric-surgery/
3.    http://www.diabetes.org/news-research/research/research-discoveries/recent-advances/changes-in-amino-acid-levels.html
4.    O'Brien P, Dixon J, et.al. (2002) The Laparoscopic Adjustable Gastric Band (Lap-Band): A Prospective Study of Medium-Term Effects on Weight, Health and Quality of Life. Obesity Surgery
5.    Monte S, Caruana J, et.al. (2012) Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus. Surgery

The Role of Inflammation in Depression and its Treatment

Dr. Charles Raison, MD of the University of Arizona is an Associate Professor of Psychiatry and Family and Consumer Sciences.  He has also been a speaker with “Ted Talks.”  Today (09/17/13), he gave a talk at the Levy Cancer Center called, “Coming to Our Senses: Implications of Embodiment or the Pathogenesis and Treatment of Major Depression.”  In his research dedicated to the treatment of depression, he discovered a direct correlation between depression and inflammation.  Furthermore, he found that in those with depression whose inflammation was greatest, the treatment outcome was best.

Dr. Raison explained he used different treatment methodologies to demonstrate his theory, that without treating the brain directly for depression, subjects would have improvements in their depression.  In one experiment, he placed subjects in a whopping 140-degree vessel for two hours, with their heads outside the heated chamber.  Depressed patients tend to have high core body temperatures and sweat very little.  He believed the outcome for this first treatment was that the brain “reset” the core temperature, and with the system running cooler, depression diminished. 

In another, he treated patients with “a potent anti-inflammatory,” similar to the brand “Humira,” or with placebo.  He was excited to see that half of the patients treated had diminished depression.  The twist, however, was that one-quarter of the patients were from the anti-inflammatory-treated group, while one quarter were from the placebo group.  Those subjects in either of the two experiments whose outcomes were best, were those whose level of inflammation was highest at the beginning of the treatment period. 

Gut Bacteria is a better predicator of Type II Diabetes, Obesity and Inflammation!

     According to the article "This Factor May Indicate Your Risk for Diabetes, Obesity, and Inflammation" from 2012 reporting that a certain type of bacteria can predict whether you can possibly have Type II diabetes. The study states the bacteria in your gut is a better indicator for Type II Diabetes than anything which can be found in the gene pool. The research hypothesized that lean people have different bacteria than people who are obese. Scientists inoculated mice with the bacteria that supposedly make individuals obese, the mice then began gaining weight.
     The article continues on about inflammation research dealing with pregnant women in Finnish women. The women have the same bacteria within their gut and displays similar conditions to people with Metabolic Syndrome. (Metabolic Syndrome is a series of conditions in which a person has obesity, high blood pressure, high blood sugar and inflammation). The research links the inflammation on a bacteria called Proteobacteria. They again tested this on mice and the mice also gained weight and had high levels of glucose levels.
     In the last section, the article begins talking about eating fermented food rather than probiotic supplements. The fermented foods contain more "good" bacteria that can help the body.
     Although this sounds credible, there are no specifics about the name of this bacteria or the company or school the research is coming from. Even if this research were credible, there is also no direct explanation of how this can be an predictor of Type II diabetes within the article expect for one sentence in the very beginning. Throughout the article, the writer remains consistent in the lack of credibility about obesity and inflammation. There were no credible sources of why fermented foods would be a good way to get probiotic bacteria into the body.

Arizona 7th worst in youth obesity!

Back when I was a kid, I would come home from school, do my homework, and then go outside to play until dinner time (bikes, roller-skates, four-square, it didn't matter)...My friends were the same way...and there weren't many obese children around.
Fast forward to 2013 and new statistics just coming out that for 2010-2011, although the national % of obesity children is leveling off (finally), some states such as Arizona actually saw an increase in youth obesity (from 17-19% of all children falling into this category).

Here's a link to the MSNBC page about the overall numbers...the Arizona statistic I heard on the news...

http://www.nbcnews.com/health/exercise-diet-habits-improving-among-youth-study-8C11167235


Why do you think we're seeing such a discrepancy? What are the consequences of obesity in children? What can we do as future healthcare professionals (or should this be our problem)?

Obesity and Inflammation, pro and anti

The recent acticle, "Inflammation in Obesity-related Diseases," (1) is an excellent article but must be broken into components in order to truly appreciate the wealth of information it has to offer.  Here I will provide only a brief review of the pro and anti inflammatory adipokines that may, in the future, be targeted by pharmacology.  Linking obesity and the roles of adipocytes and lymphocytes (the non-adipocyte cell fraction of adipose tissue) to the production of adipocytokines, the article identifies those which are upregulated (and induce insulin resistance and other inflammation-related diseases) and those which are downregulated.  The article is best summed up by this quote, "The reciprocal regulation of pro and anti inflammatory adipocytokines is an important feature of adipose tissue-based inflammation."

Amongst the upregulated pro inflammatories are leptin, TNF alpha, IL6, resistin, and MCP1, while the downregulated anti inflammatories include adiponectin, IL-1RA, IL-10.  Leptin upregulates lymphocyte development, cytokine expression, proliferation and apoptosis, and in the company of other pro inflammatory adipocytokines, trigger JNK-1 and IKK beta to effect changes in inflammation and glucose homeostasis.  Both JNK-1 and IKK beta have been known to be associated with atherosclerosis and steatohepatitis as well. While the pivotal point of adipose cytokine production is not yet known, the article makes clear that "The root cause of inflammation  [is] obesity," with adverse effects reversed with weight loss.  Know, however, that not all adiposity is equal, and visceral  is, hands-down, the largest contributor to adipocytokine production when compared to subcutaneous.

As we look to the future of personalized pharmacology, "adipocytokine-based phamacotherapy for metabolic disease is on the horizon," and may include neutralizing IL-1 in order to improve insulin resistance and reduce inflammation or targeting JNK or IKK beta.

1.  Surgery 2009;145:255-9
doi: 10.1016/j.surg.2009.09.038

Averting Inflammation and Vampires

Allium sativum (garlic) and Allium cepa (onion) are evaluated as anti-inflammatories in the Journal of Nutrition and Metabolism's article, "Garlic and Onion Attenuates Vascular Inflammation and Oxidative Stress in Fructose-Fed Rats" (1).  With firm rationalization that the addition of simple sugars, particularly fructose, as main dietary changes, coincide with the incidence and prevalence of METS and its sequelae (diabetes, obesity), and most importantly, endothelial dysfunction as it relates to inflammation, fructose-fed rats (FFR) are treated with known and proposed anti-inflammatories to determine treatment outcomes.  Endothelial dysfunction results from reduced eNOS activity, increased oxidative stress (ROS), and increased synthesis of vascular cell adhesion molecule (VCAM-1, a monocyte binder) and leads to cardiovascular changes from vascular remodeling.

Young, 30-day old Wistar rats were fed their standard diets for 14 weeks under controlled conditions. During the first six weeks, 80% of the rats were fed a 10% fructose/water solution, with the remaining rats used as control.  After six weeks, FFR were subdivided into four groups which were either untreated or treated with tempol (a potent anti-inflammatory), garlic, or onion.  At the end of the 14-week period, the rats were evaluated for TBARS (markers for lipid peroxidation/oxidative stress), NAD(P)H (another ROS  marker), eNOS activity, and VCAM-1 protein expression. In order to identify desired outcomes, ideally, TBAR activity, NAD(P)H activity and VCAM-1 protein expression would be reduced, with eNOS activity increased.

Results:  TBARS were comparable to control in all anti-inflammatory-treated categories, with underperformance by onion.  Aortic NAD(P)H oxidase activity, while nearing double that of control, was significantly reduced as compared to FFR when treated with tempol or garlic, whereas onion again underperformed.  eNOS activity was comparable for control and tempol-treated FFR, with garlic slightly underperforming in comparison to onion.  VCAM-1 protein expression levels, as measured by Western blot, were high in all treated FFR and moreso in untreated FFR.

Issues to consider:  Anti-inflammatory treatments aside, the clear winners were the control rats.  Once the rats were fructose-supplemented, their food intake was reduced and their water intake increased.  This resulted in a higher energy intake and represented an average 6.5% increase in body weight over the 14-week period.  With garlic and onion alternating in efficacy as anti-inflammatories amongst the categories, the combination of the two would be worth exploring.  Unfortunately,  implementing a comparable study in humans would amount to multiple heads of garlic and onion having to be consumed, sure to keep the vampires (and everyone else) away.

1.  Hindawi Publishing Corporation, Journal of Nutrition and Metabolism, Volume 2011, Article ID 475216, 7 pages, doi:  10.1155/2011/475216.