Cocoa and Obesity Related Inflammation

In a recent study conducted by Penn State researchers, mice models were used to examine the effects of cocoa on obesity-related inflammation. Cocoa, unlike chocolate, is low in fat and sugar. It also contains polyphenolic compounds, like green tea and wine. In their study the control group of mice was fed a high fat diet, while the experimental group was fed a cocoa supplement in addition to the high fat diet. The mice ate an equivalent of 10 tablespoons of cocoa powder during a 10 week period, which is 4-5 cups of hot cocoa.

The researchers found that the mice with the cocoa supplement diet had 27% lower plasma insulin levels than those that did not have the cocoa supplement. Additionally, the levels of triglycerides in the liver were reduced by more than 32%. The mice with the cocoa supplement even saw a slight, but significant, decrease in the rate of weight gain. 

The researchers proposed two theories about obesity related inflammation and the effect of cocoa. One theory is that excess fat may activate a distress signal that activates immune cells causing inflammation. Therefore, cocoa may reduce the precursors that stimulate this distress signal. A second theory is that the high fat diet interferes with the body’s ability to keep endotoxins from entering the bloodstream through gaps between cells and that cocoa may improve the barrier function of the gut.

I found this article on Science Daily and Penn State’s News website but, I was unable to find the journal article itself. While the results of this study are impressive, I think this study could easily be translated to humans to determine if cocoa has anti-inflammatory affects in humans and how much is needed to produce these results. This would be extremely beneficial as cocoa supplements could aid obese individuals in controlling diseases like diabetes. I also think that this would be an inexpensive method of fighting obesity-related inflammation.  

Sources:

Penn State (2013, June 12). Cocoa may help fight obesity-related inflammation. ScienceDaily. Retrieved October 29, 2013, from http://www.sciencedaily.com­ /releases/2013/06/130612133134.htm

How Flight Leads to Stomach Pain for People with IBD

How Flight Leads to Stomach Pain for People with IBD

The knowledge that traveling causes stomach pain for individuals with IBD is not new; however, it was previously thought that the source of this pain stemmed from ‘travel stresses’ or infections that had been picked up along their journey. Researchers from the Swiss IBD Cohort Study studied how low oxygen levels at 2,000m above sea level affects patients with IBD. They determined that the lack of oxygen activates inflammation which is the source of the pain that the patients with IBD experience. Their study found similar results to tissue samples in lab that produced an inflammatory response during oxygen starvation.  The researchers concluded that journeys to high altitude or flights are a risk factor for IBD flare-ups within 4 weeks of traveling.

This new information can be extremely beneficial for doctors and their patients with IBD. Doctors will now be able to prescribe medications for to mitigate bowel production of inflammation in hopes of preventing the flare-ups.  Additionally, this study illustrates how environmental factors impact inflammation in IBD.

Source:

Vavricka, Stephan, Gerhard Rogler, Sandra Maetzler, Benjamin Misselwitz et al., "High altitude journeys and flights are associated with an increased risk of flares in inflammatory bowel disease patients." Journal of Crohn's & Colitis(2013) Online.

LSD...the new miracle drug for inflammatory disorders???

According to a recent article on Medical News Today, a study performed by Charles Nichols, pharmacologist at LSU Health Sciences Center, has concluded in the use of LSD as a very potent anti-inflammatory. The research was directed toward TNF-alpha, a potent pro-inflammatory adipokine. The researchers found that when serotonin 5-HT2A receptor proteins were activated, the receptor proteins impressively blocked TNF-alpha induced inflammatory responses. But how did these researches activate serotonin 5-HT2A? With the use of a drug belonging to the LSD family, of course! The researchers found that when TNF-alpha was injected into mice after serotonin 5-HT2A receptors were activated, there was a near complete inhibition of inflammation in comparison to mice whose receptors were not activated and had a full inflammatory response. Interestingly and most relevant to the topic of the past two weeks, the tissue that this procedure had the most powerful effect on was intestinal tissue, and doses of less than 300 times lower than what is required to illicit any behavioral effects of the drug were found to induce this powerful anti-inflammatory effect!

Although extremely interesting, LSD is a serious hallucinogenic drug with severe side effects, and although this study makes it a point to establish that only very minute doses are needed to illicit an anti-inflammatory response, they fail to mention whether or not the mice developed any side-effects from the drug. I think that a good follow up study would be to study any side effects that occur after administering the small doses of this drug over a long period of time to mice. Even in low doses, I am convinced that over a long treatment period, mice would eventually develop some sort of side effect because of the LSD families very potent abilities to cause severe mental abnormalities. Also, the drugs belonging to this family are severely addictive, it would be nice to see a follow up study done on how these mice react once the drug isn't going through their bodies. What are your thoughts and opinions?

1.) Louisiana State University Health Sciences Center. "Target discovered for new Rx class for inflammatory disorders." Medical News Today. MediLexicon, Intl., 7 Oct. 2013. Web.
25 Oct. 2013. <http://www.medicalnewstoday.com/releases/267019>

SMOKING AND ADDED SUGAR INTAKE ARE INTERACTIVE RISK FACTORS IN CD?

This study (1) looks at the association between added sugar consumption of less than and greater than 50 g per day and smoking relative to CD.  The study consists of a repeat or secondary questionnaire sent to 104 CD patients and 153 controls 24 months after an initial study.  The initial study, the author says, found strong associations between refined sugar intake and CD and between smoking and CD.  Ultimately, no further association between CD and sugar intake was found in the smoker population, and a conclusion was drawn that the lack of a compounding influence could suggest that increased sugar intake and smoking work through a common mechanism to bring about CD.

            While the above conclusion is concurrent with data, an important piece of information is omitted:  results also showed that there was an additional correlation amongst smokers as well, such that whether they be control or patients with CD, the no sugar added category also was found to equate.  In reading the abstract, one might be misled into believing that the correlation amongst smokers with increased sugar intake whether or not diagnosed with Crohn’s is the only one.   Because the correlation also exists with no sugar added, one might conclude, alternately, that added sugar does not provide a risk for Crohn’s, since smoking without added sugar is a sufficient risk factor to provide comparable results.  Ultimately, smoking, without added sugar or with over 50g of sugar added is found to result in comparable risk for Crohn’s.  Amongst non-smokers, both the no added sugar and the low added sugar groups showed comparable risk.

            Sample size and patient matching to age (within two years) and sex to two controls is a significant coup and not widely accomplished in human studies.  Future direction for this study will include, as many references indicated, looking at newly-diagnosed cases rather than two-year old cases for better determination of study results.

1. Katschinski, B., et al. "Smoking and sugar intake are separate but interactive risk factors in Crohn's disease." Gut 29.9 (1988): 1202-1206.

           

Reducing the risk of IBD with exercise

Here is a brief fact before moving on; approximately 1.4 million Americans are diagnosed with IBD before the age of 30! Keep in mind that there was a geographical gradient in relation to IBD and that our quality of living makes us susceptible to acquiring IBD. Another aspect to keep in mind is your family history. So, have you all noticed that reducing the risk for the majority of the topics that we have discussed in class have some association with exercising? That should allow for us to come to a safe conclusion, exercising is good for us! Here is a little bit more motivation for you; exercising can reduce the risk of you acquiring inflammatory bowel disease (IBD). This is not a cure by any means but exercising would increase both your muscle strength and bone health as well. Exercise training has to potential to reduce the symptoms of acute colitis. Meaning that it would decrease the over-production of the pro-inflammatory cytokines. Not only is the over-production of pro-inflammatory cytokines associated with IBD, but it contributes rheumatoid arthritis, asthma, allergies, and lupus.

1. http://www.nutritionmd.org/consumers/gastrointestinal/ibd_nutrition.html

2. http://www.journal-inflammation.com/content/9/1/30
3. http://www.ccfa.org/assets/pdfs/ibdfactbook.pdf

Correlation between Sleep and Crohn's Disease?

In a recent study performed by the Division of Gastroenterology at Rabin Medical Center, researchers were searching for a correlation between the quality of sleep of patients with Inflammatory Bowel Disease and more specifically in patients with Crohn's Disease. The study included a total of 144 participants, 108 being patients suffering from Crohn's Disease and who were undergoing treatment at an IBD clinic and 36 being healthy individuals who volunteered their time for the study. All 144 participants completed demographic questionnaire's as well as the Pittsburgh sleep quality index (PSQI). A high score on the PSQI is indicative of poor sleep quality. The 36 Crohn's Disease patients also completed a Crohn's Disease activity index and were divided into two groups based on the results of this activity index. Patients with a score less than or equal to 150 were placed into the inactive disease group, and patients with a score greater than or equal to 150 were placed into the active disease group. The active Crohn's Disease patients had a significantly higher PSQI (8.6 +/- 2.4) as compared to the inactive Crohn's Disease particpants (4.6 +/- 1.9) and the healthy participants (5.1 +/- 1.7), indicating that there is indeed a positive correlation between sleep quality and Crohn's Disease.

Do you think that this correlation between sleep quality and active Crohn's Disease is only a matter of the amount of discomfort that these patients are experiencing? Why or why not? Do you think that impairment of sleep quality in active Crohn's Disease patients could ultimately lead to even poorer health? Had you been one of these researchers, what other tests would you have performed and why?

1.) Gingold-Belfer, R., N. Peled, S. Levy, N. Katz, Y. Niv, R. Fass, G. Fraser, and R. Dickman. "Impaired Sleep Quality in Crohn's Disease Depends on Disease Activity." NCBI (2013): n. pag. Pubmed.gov. PubMed, 11 Oct. 2013. Web. 22 Oct. 2013. <http://www.ncbi.nlm.nih.gov/pubmed/24114045>.

Worms, genes, cleanliness and... Breast milk!?

After reading one of today's headlines on 'tainted breast milk sold over the internet' (Really! here's the site - http://www.npr.org/blogs/health/2013/10/21/238797756/breast-milk-bought-online-has-high-levels-of-bacteria) and having finished reading, in great depth, about Ulcerative Colitits (UC) and Crohn's Disease (CD) my mindset thus became, "how are IBD and breast milk related?" Interestingly, I was not surprised to find several articles and reviews on the topic. 

According to the WHO (1), globally, only 38% of children ages 0-6 months are exclusively breastfed. Naturally (in my mind), the US falls short of this average - according to the CDC (2) 16.4% of American children are exclusively breastfed at 6 months of age (down from 37.7% at 3 months of age). Until recently, breastfeeding was in a steep decline, the increasing knowledge of the tremendous benefits of breast milk has allowed for an uptick in the past decade. 

As discussed previously, there are many theories as to what causes IBD. Many speculate that genes play a large role as do the lack of particular gut flora due to 'modern cleanliness' of foods and especially water (3). Similarly, other environmental factors are thought to play a role as well as lifestyle choices - i.e. smoking. With an increase in women in the workforce as well as the increase in easily accessible infant formulas and their convenience (not-to-mention the massive push to use it in years past), I would venture to argue that in combination with genetics, our environment, and many poor lifestyle choices, the lack of proper nutrition for our infants plays a huge role. It is well known that breast milk has tremendous protective properties when referencing the immune system; properties that are not fully known nor easily synthesized. 

Klement et. al. (4) suggests that although more research on the topic is necessary, breastfeeding is indeed associated with lower risks of Crohn's Disease and Ulcerative Colitis. Furthermore, Barclay et. al. (5) suggest a possible protective effect of breast milk for early-onset IBD, demonstrated by data of statistical significance. 

I agree that more work on the topic is indeed necessary in order to fully understand whether breast milk is truly protective, however the protective properties do not end with IBD. Much research is being conducted on the beneficial impact of breast milk and obesity, asthma, allergies and other [auto]immune disorders. Despite only being (strongly) correlated, is it not easier to just play it safe in all facets and breast feed your baby for a mere 6 months? I understand all the difficulties associated with breastfeeding but do we not want the best for our children and future generations? After all, breastfeeding in no way harms one's child...

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1.    http://www.who.int/mediacentre/factsheets/fs342/en/index.html

2.    http://www.cdc.gov/breastfeeding/pdf/2013BreastfeedingReportCard.pdf

3.    Korzenik, J. (2005) Past and current theories of etiology of IBD: Toothpaste, worms and refrigerators. Journal of Clinical Gastroenterology

4.    Klement, E, et.al. (2004) Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis. American Journal of Clinical Nutrition

5.    Barclay, A, et. al. (2009) Systematic review: The role of breastfeeding in the development of Inflammatory Bowel Disease The Journal of Pediatrics

Stroke and IBD: A Report and Review

            This article was a great find because in our last class we ended with the Stroke group and began discussing Irritable Bowel Disease. The article presents two stroke cases in which each patient had been previously diagnosed with a classification of IBD called Ulcerative Colitis. Neither patient had any history or risk factors that would lead to cerebral vascular complications, but both were found to have ischemic infarction after being admitted to the hospital.

            The first patient had hemiparesis, on arrival, meaning that he was able to move but with much limited strength. In the discussion it is first mentioned that "Deep vein thrombosis with or without pulmonary embolism remains the most common vascular event complicating inflammatory bowel disease" and continue to say that the CNS is not usually involved in these thrombotic events. Could it be that the thrombotic event in the enterogastric region can lead to global ischemia in the cerebral region? This would be a good theory, but it doesn't explain how an event so distal would lead to the ischemic and focal infarct seen in the tomography and CT that was taken of both patients. The paper states that "Inflammation during episodes of increased disease activity is a potent prothrombotic stimulus due to fibrinolysis inhibition," so it may have the lack of prevention in clotting blood played a role. It even further explains the pro-inflammatory cytokines that are hyperactive in IBD, but what caught my interest was that "studies have also examined the role played by platelet-leukocyte aggregates (PLA) which are increased in patients with IBD." My last article I had discussed in class failed to analyze the Platelet-Leukocyte aggregation that was seen in the MCAO-R rat group. It's been shown that increased thrombosis risk is recognized in IBD patients and that "PLAs cause microinfarction and exacerbate thrombus formation by enhancing the production of tissue factor." It is possible that these heightened inflammatory activities due to IBD can lead to global or focal ischemic stroke, which has its own increased inflammatory response as well.

            There is little, but growing, awareness of stroke complications in IBD patients. The article provides brief overview of how patients, especially those diagnosed with IBD, should be treated with "aspirin and modification of atherosclerotic risk factors" in order to prevent thrombolytic or embolic events. There is still need for more research in cases such as the ones presented to understand this increased coagulation and the pathology that led these patients to have focal ischemic infarct in the cerebral region. Was IBD actually the cause of their strokes or does it go deeper than that? feel free to comment or add anything on your mind.

Citation

Deepak, Joshi. "Stroke in Inflammatory Bowel Disease: A Report of Two Cases and Review of the Literature." Thrombosis Journal. N.p., 21 Mar. 2008. Web. 14 Oct. 2013.             <http://www.thrombosisjournal.com/content/6/1/2>.

Surgical Treatment for Crohn's Disease

Patients with Crohn’s disease will have scarring in their intestine eventually. If the medication/treatments don’t works for the patient, in other words the intestine is damaged to the point where the segments of the intestine become narrow, they would have a strictureplasty performed. A strictureplasty surgery is where the surgeon cut opens those segments to enlarge the area for passage of waste. When the Crohn’s disease have come to a point where there are holes in the intestine, sections would have to be removed and reattached the healthy ends. After this surgery, usually the patients would have to do another one of these surgeries for damaged sections again. For patients who have the severe outbreak of Crohn’s disease will need to have their whole colon removed and rectum as well if infected. Their waste would be collected in a bag that requires to be emptied several times a day. There are two types of surgery for this, one is call proctocolectomy, where the entire colon and lower part of the rectum along with the bowel movement muscles are removed. The other surgery is called ileostomy, where the small intestine opening is connected to a small opening in the lower right corner of the abdomen done by the surgeon with a anostomy bag placed over that opening for collecting waste.

After reading about the surgery portion for Crohn’s disease, I feel like the ones who has to have their whole colon and rectum removed would feel horrible having to empty their bags several times a day because of the Crohn’s disease that requires them to remove their whole colon and rectum. What do you think about having your whole colon and rectum removed and having to empty you bag of waste several times a day?

Work Cited:
Simon M.D., H.. N.p.. Web. 17 Oct 2013. <http://health.nytimes.com/health/guides/disease/crohns-disease/surgery.html>.

Didn't find worms or fecal transplants as an appealing treatment for IBD?

Then maybe you could try stem cells!

Researchers at the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge and at BRIC, the University of Copenhagen, Denmark, did a study that tested the effect of stem cells as a treatment for Inflammatory Bowel Disease (IBD) in mice. They isolated fetal stem cells and grew them in a laboratory for a long period of time. (They were able to isolate similar cells from adult mice and humans called induced Pluripotent Stem Cells (iPSCs).) Once the cells were added to the digestive tract of the IBD induced mice, within 3 hours, the stem cells attached to the gut lining and started repair. Of course, one risk with cells that divide easily and happily in their new environment would be tumor formation.  However there was no evidence of this in the study. 

Since this appears to be a treatment to repair damage, I would think the patient would still have the symptoms associated with the disease (one has to have damage to repair damage).  Which are often, abdominal pain, diarrhea, and bloody ulcers in the intestine wall, which lead to bloody stool.  With the description of the stem cells creating a plaster over the damaged areas and integrating with gut cells, I envisioned it to work like a band aid, do you think this would have beneficial long-term effects? Or cause issues such as tumors?

This study was done in mice and would have to be able to transfer to a human model.  As stated they did find similar cells in humans! What do you think would be an issue (if any) to transfer this study to humans?

1. Jensen et al. Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury. Cell Stem Cell, October 2013
2. Wellcome Trust (2013, October 17). Stem cell transplant repairs damaged gut of inflammatory bowel disease. ScienceDaily. Retrieved October 17, 2013, from http://www.sciencedaily.com­/releases/2013/10/131017135210.html

Worms and The Treatment of IBD

This particle article was my favorite of the Inflammatory Bowel Disease (IBD) lists because throughout the years, the usage of parasitic worms in either weight loss and prevention and/or suppression of a disease has been circulating the news. This review article will focus on a specific parasitic worm, known as Helminth, and how its derived molecules and assist in the treatment of IBD.

The two major diseases that are associated with IBD is Crohn's disease and Ulcerative colitis. Crohn's disease would affect the intestines but may also occur anywhere from the mouth to the anus and can cause a malabsorption of nutrients while ulcerative colitis affects the lining of the large intestine and rectum causing inflammation. One major point to take away from this article would be that genetic factors and environmental factos both contribute to the damaging muscosal immune response which would open the door for the introduction of the Hygiene Hypothesis. The Hygiene Hypothesis for IBD suggests that the lack of exposure to infectious agents, such as helminth, as a result of improved living standards and medical conditions which modulates the development of the immune system and increase the risk of immune disease. The major cause in low-incidence areas are a change in the lifestyle and one way to view this change would be looking at the socioeconomic level. IBD is seen more in patients that have a higher socioeconomic status due to their beter sanitation conditions. The second factor that supports the hygiene hypothesis would be the inverse relationship between infant mortality rates and the incidence of IBD. 

Gastrointestinal inflammation during Crohn's disease is Th1 mediated. The second type are the Th2 cells that enhance the elimination of the parasitic helminth infections and supports allergic responses. According to the article, the host brings about a strong Th2 immune response to provide protection against the worm colonization. The last would be the Th17 cells which are critical for the development of inflammation while the Treg cells help in the prevention of autoimmune diseases including the inhibition of IBD. On a side note, worms can be used to down-regulate the immune response! Surprisingly, Helminth colonize more than a third of the worlds population which is why using a geographical distribution to demonstrate the prevalence of Helminth is beneficial. This parasitic worm is common in developing countries and there is an inverse relationship between frequency of the worm colonization and the prevalence of IBD. 

Since there is no such thing as a perfect medication, as far as I know of that does not have any side-effects, the treatment of patients with living Helminths had some drawbacks. Some of those drawbacks was that the parasite did not stay were it was suppose to be. Here is an example: a Crohn's disease patient was given five oral doses of Trichuris suis which caused an infection in the ileocecal regions and found a sexually mature male worm within the cecum. This can also result in diarrhea and abdominal cramps. Luckily, Helminth-derived immunomodulatory molecules can contribute to the anti-colitis effect without the helminth infection. To summarize this article up, helminth-derived molecules hope to be effective in the treatment of the IBD without having to worry about having the parasite living inside the individual. 

References:
1. Ruyssers, Nathalie, De Winter, Benedicte, De Man, Joris G., Loukas, Alex, Herman, Arnold G., Pelckmans, Paul A., and Moreels, Tom G.. "Worms and the Treatment of Inflammatory Bowel Disease: Are Molecules the Answer?." 2008 March 5. Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, University of Antwerp, Division of Infectious Diseases, Queensland Institute of Medical reseach, Laboratory of Pharmacology, University of Antwerp, and Division of Gastroenterology and Hepatology, University of Antwerp. 

Herbs Used to Treat Inflammation

As a response to interest expressed in  “naturopathic remedies,” the following herbs are listed in a review by Michael Moore of the Southwest School of Botanical Medicine in Bisbee, AZ, as affiliated with reduction of inflammatory states (1).  I found the reference to be quite an interesting compendium of herbal cures which also listed formulas, compounds and essential oils.  For further information, you can see his homepage at:  http://chili.rt66.com/hrbmoore/HOMEPAGE/HomePage.html

Aconitum – mucus inflammations

Acorus Calamus – flatulence with inflammation

Agropyron Repens  --  renal weakness with inflammation

Anemopsis Californica – chronic sinusitis with inflammation, acute prostatis with inflammation

Angelica – flatulence with inflammation

Byronia -- Acute mastitis, with swollen lymphatics, marked inflammation

Bursera -- Chronic cystitis/urethritis without active inflammation

Caulophyllum -- Uterus, inflammation, Labor, delayed, from fatigue, weak uterus with history of inflammation

Commiphora -- Acute aphthous stomatitis with painful inflammation, Chronic cystorrhea w/out active inflammation, in exhausted, feeble states, Chronic nephritis without active inflammation

Dioscorea -- Uterus, inflammation, with cramps

Ephedra Viridis -- Acute cystitis/urethritis with inflammation and irritation, Hay fever, in general; and in particularly sensitive individuals

Equisetum -- Acute cystitis/urethritis with inflammation and irritation

Euphrasia -- Acute conjunctivitis w/sharp sinus pain; hyperaemia w/rhinitis, frontal headache,

sneezing; acute inflammation of the eyelids; also as an eyewash for runny eyes

Gelsemium -- Trigeminal neuralgia from cold, caries, or gum inflammation

Gossypium -- Uterus, inflammation; or prolapse

Harpagophytum -- Anti-inflammatory in arthritis, Gout, for inflammation and for the hyperuricemia

Matricaria -- Gout, for inflammation (as a bath)

Myrica -- Chronic sinusitis with inflammation, catarrh, stuffy heat, Flatulence with inflammation, Irritable bowel syndrome with chronic ileocecal inflammation or cramps

Trillium -- Uterus, inflammation

Virburnum Opulus -- Uterus, inflammation

Virburnum Prunefolium -- Uterus, inflammation

1.        Moore, Michael. Specific indications for herbs in general use. Southwest School of Botanical Medicine, 1997.

More on stroke and inflammation

As we have discussed these past two weeks, stroke inflammation is a leading cause of death in victims. The suppression of these inflammatory cytokines using drugs can potentially reduce the volume of infarction. In this study, researches tested the thrombolytic drug rtPA that can possibly save brain tissue known as ischemic penumbra. This drug works by degrading the thrombus in the artery and restoring the circulation distal to the obstruction. However, this is a neurotoxic drug that cannot leak into the blood brain barrier, therefore, should be controlled and restricted to the vascular compartment.

Researchers have made clear that anti-inflammatory strategies in animal stroke models after several days salvage viable brain tissue. These drugs can lengthen the therapeutic window and reduce the side affects of rtPA. Investigators think that anti-inflammatory strategies should receive more attention because they have a broad application for all aspects of stroke.

This article was very interesting and similar to the E-selectin basic review we looked at last week.

M. Nilupul Perera, Henry K. Ma, Shuji Arakawa, David W. Howells, Romesh Markus, Christopher C. Rowe, Geoffrey A. Donnan, Inflammation following stroke, Journal of Clinical Neuroscience, Volume 13, Issue 1, January 2006, Pages 1-8, ISSN 0967-5868, http://dx.doi.org/10.1016/j.jocn.2005.07.005. (http://www.sciencedirect.com/science/article/pii/S0967586805003413)