Oxygen levels influence efficacy of anti-inflammatory therapies

Researchers from the University of Edinburgh Medical School isolated neutrophils and incubated them at 21%, 10%, 5% and 1% oxygen. Next they added an inflammatory environment to these cells and studied the effects of anti-inflammatory glucocorticoid drugs on the neutrophils. They found that Dexamethasone (an anti-inflammatory glucocorticoid) promoted neutrophil survival at 21%, 10% and 5% but not at 1% oxygen. This means that at areas with less oxygen profusion react differently to the same drug. They believe that the one size fits all mentality to anti-inflammatory drugs may be "overly simplistic". They believe this is the mechanism behind patients differing responses to the same anti-inflammatory drugs. This could make the treatment of conditions like COPD and asthma different from rheumatoid arthritis because of the oxygen levels present. The studies authors hope that further research into this area could bring more targeted anti-inflammatory drugs with fewer side effects.

References:
http://www.jleukbio.org/content/94/6/1285.full.pdf+html
http://www.sciencedaily.com/releases/2013/12/131202121536.htm

Anti-Inflammatory action of mucus

Researchers from Icahn School of Medicine found that dendritic cells of the gut could actually capture mucus along with bacteria and food antigens. Furthermore the mucus actually "constrains the immunogenicity of gut antigens by delivering tolerogenic signals". Instead of just a protective barrier and lubricant of the digestive tract mucus is involved in the immune homeostasis of the intestinal tract. They said that the mucus barrier is organized around hyperglycosylated mucin (MUC2). MUC2 is supposedly taken up by gut antigen-sampling dendritic cells. These glycans which were associated with MUC2 caused an anti-inflammatory response within the dendritic cells which sampled them. This anti-inflammatory action was proposed to be from assembling galection-3-Dectin-1-FcyRIIB receptor complex which acivated beta-catenin. This transcription factor inhibits transcription through nuclear factor kappaB which results in inhibiting pro-inflammatory cytokines but not tolerogenic cytokines. I find it fascinating that the article we discussed in class on the benefits of curcumin were largely due to its roll in inhibiting  nuclear factor kappaB. It seems that curcumin uses the same pathway to modulate inflammation as our own mucus.

The researchers proposed that it would be beneficial to find a way to manufacture mucus for supplementation for patients with gastrointestinal tract disorders such as inflammatory bowel disease and Crohn's. These findings could also shed light on new treatments for cancer because this is a mechanism used by malignant cells to evade the immune system. Apparently some cancer cells produce mucus with MUC2 which the researchers imagine might down regulate the immune response allowing the malignant cells to survive.

References:
http://www.sciencemag.org/content/342/6157/447
http://www.ncbi.nlm.nih.gov/pubmed/19723087

A Cretan Mediterranean Diet Can Prevent Stroke

We all know that nutrition has a major role on stroke prevention. I thought this study was interesting because it was based on a specific Mediterranean diet.

In this study it is shown that a Cretan Mediterranean diet has reduced stroke and myocardial infarction. The recruited 423 survivors of myocardial infarction were randomization to a Mediterranean diet or a Western diet. The patients assigned to the Mediterranean diet had a 60% reduction in cardiac death and MI over 4 years compared with the patients on the Western diet. This Mediterranean diet contained high beneficial oils, whole grains, fruits, vegetable, and low in cholesterol and animal fat.

They point out that a key problem with the Western diet it that North America fails to distinguish between kinds of fat and between red meat, poultry, and fish. I thought it was interesting that they mention that the mantra that “fat is bad” has led to reduced fat intake and increased carb intake. This misconception has led to harmful cardiovascular effects.

Also, a VISP trial was done on patients responding to B vitamins had significant reduction of stroke, death, and coronary disease. They make an exception for this vitamin because it lowers homocysteine. By lowering homosysteine they can reduce thrombosis, impaired endothelial function, and oxidative stress.

They conclude that patients at risk of stroke should consume a Cretan Mediterranean diet and to take higher doses of B12. You can never go wrong with eating fruits and vegetable of all different colors. The more colorful the better it is for you. Nutrition should really be more appreciated because what we consume now will reflect on us in the future.  

Nutrition and Stroke Prevention. American Heart Association. 27 July. 2006. Web. 08 Dec. 2013. <http://stroke.ahajournals.org/content/37/9/2430.long>

Finals...Stress...IBS !

Yes that rhymed ;)

      So as we all know, it is finals time! While looking around in Pharmacy Times I came across an except that wanted to share, since it relates to any and all students out there! In Pharmacy times there is an excerpt that claims that "Students with IBS symptoms have higher stress levels". The article mentions that College students with IBS symptoms experience higher levels of "mental strain and chronic stress" than their peers without IBS symptoms. After class discussions I wouldn't doubt that individuals with IBS experience higher levels of stress on a daily basis, but I also believe our body works in mysterious ways, and I wouldn't be surprised if around finals time as stress levels are extremely high that IBS symptoms begin to appear in even those individuals who have not been formally diagnosed with the disorder.

     For this experiment researchers recruited 176 German university students with IBS-like symptoms, and 181 students without (only 2 had reported being formally diagnosed by a physician). The gathered information from each participant through studies, that asked them questions about their stress levels, and their answers were analyzed and scaled based on chronic stress and IBS symptoms.

     They found that IBS-like symptoms were higher in students who experienced higher levels of chronic stress. As i'm sure many of us have realized that 1.5+ weeks of late nights, early mornings, no sleep, greasy food, snacks (peanut m&m's are a must), having a job, and a lack of exercise can certainly feel like a gigantic heavy load of chronic stress. In the study they also found that there was a positive correlation between IBS symptoms and stress levels. Just a reminder these IBS symptoms can include: abdominal pain, bloating, cramping, diarrhea and/or constipation etc. Stress factors that tended to increase these IBS symptoms were: anxiety, work over load, social tension, and job dissatisfaction.

       Another aspect I felt was key that they mentioned in this study that the main difference in between students with IBS symptoms who were under the care of a physician vs. those who did not, was that students who frequented doctors typically had more severe symptoms but otherwise, there were no difference in the stress levels. So if your belly starts to ache while you're spending all your free time in the library, or at Coffee Exchange, or wherever you choose to frequent, it may be a sign that your body is handling increased levels of stress. So maybe, take a deep breath, relax, take a mini break and try Karens sudoku puzzle!

Good Luck with Finals!! May the curve be ever in your favor! 


Students with IBS Symptoms Have Higher Stress Levels. Pharmacy Times [serial online]. July 2013;79(7):62. Available from: Academic Search Complete, Ipswich, MA. Accessed December 9, 2013.

http://www.mayoclinic.com/health/irritable-bowel-syndrome/DS00106/DSECTION=symptoms

Does Inflammation Contribute to the Development of Depression?

So in doing some reading for another class, I came upon a news article in the textbook that was titled “Does Inflammation Contribute to the Development of Depression?” and well that caught my attention and brought me back to this class. Research shows that through systemic infection, activation of the immune system increases proinflammatory cytokines like interleukin (IL)-1α and IL-β, tumor necrosis factor-alpha (TNF-α), and IL-6. These cytokines are produced in the periphery serve to regulate the inflammatory response to pathogens. It said that cytokines will also enter the brain and modulate a widespread brain cytokine system consisting of the neurons and glial cells with the cytokine receptors involved in altering brain function. That with cytokines on the brain it creates symptoms of sickness like loss of appetite, malaise, and avoidance of social interactions. These symptoms overlap key features of depression like fatigue, reduced appetite, altered mood and thoughts.

            It says that yes the sickness symptoms may go away in time and be reversible, but there may be certain people that may be too vulnerable to overcome it and be exposed to the inflammation for a longer period of time and in that being exposed to depression symptoms as well. And also they made a connection between the drug treatments used for depression, like antidepressants which reduce the activation of proinflammatory cytokines. So in that, the development of drugs that would target inflammation, it would also be inhibiting the development of depression. I thought this was really interesting; it would kill 2 birds with 1 stone since depression is one the common mood disorders that are the leading cause of disability in the U.S. and throughout the world.   

McCance KL and SE Huether. 2010. Pathophysiology: The Biological Basis for Disease in

            Adults and Children (6nd ed.) Mosby-Year Book, St. Louis.

 

Little about MS

I am particularly sensitive when MS comes up as a topic because my Uncle was diagnosed with MS three years ago. I was desperate to find something, anything that may treat or lessen relapses even for a little bit. As I was looking for some information, I came across one short TEDxTALK video, which had Terry Wahls, M.D. as a guest speaker. She was diagnosed with Relapse-Remitting Multiple Sclerosis in 2000. In 2007, she hit the point where every day tasks were extremely difficult to do due to progressed symptoms of MS. In the same year, she changed her focus to diet and tried to tackle the disease by using holistic medicine. 6 months later, she became the first one to cure MS, and to be free from the disease. Her story is extraordinary and worth spending time watching it. Below is the link to the video.

http://www.youtube.com/watch?v=KLjgBLwH3Wc

Preventing Brain Diseases with Sudoku Puzzles!

So after all the articles we've read and them concluding that stimulating the brain and not just exercising the body has great benefits towards preventing diseases like Alzheimer's and Parkinson's. I thought why not post a puzzle or activity to work our brains, since  learning something new or challenging our minds are two of the ways to postpone diseases as long as we can. And the sooner we start the better. So here are the instruction on how to work on a Sudoku Puzzle, in case you're not familiar with this game and also a link to where you can complete one at your own difficulty level and get timed on it. Have fun! :) 

http://mypuzzle.org/sudoku

 

Anti-inflammatory and Antibiotic Treatment for Cough Symptoms

A recent study in Spain, researched if patients treated with oral anti-inflammatories or antibiotics would improve cough symptoms in patients with uncomplicated acute bronchitis.  

Patients aged 18 to 70, from nine primary care centers in Spain, with symptoms of a respiratory tract infection lasting less than one week, with cough as the main symptom, the presence of discolored sputum (the mucus coughed up from the lower respiratory tract) and at least one other symptoms of lower respiratory tract infection such as breathing difficulty, wheezing, chest discomfort or chest pain.  The patients were randomly placed in three groups, ibuprofen 600 mg three times a day, amoxicillin-clavulanic acid 500 mg/125 mg three times a day and placebo three times a day for ten days.  The number of days after treatment with a frequent cough was recorded.

The results demonstrated that there was no significant difference between the different treatments.  The frequent cough lasted 9 days in patients taking ibuprofen and 11 days in patients taking placebo or amoxicillin-clavulanic acid.  The authors concluded that anti-inflammatory and antibiotic treatment was not significantly effective in treating cough symptoms in patients with uncomplicated acute bronchitis.

I think this was a good study they did, to test if anti-inflammatories or antibiotics improve the most common symptom associated with patients who have lower respiratory tract infections, cough.  This study, however, was unsuccessful in proving that anti-inflammatories or antibiotics improve cough symptoms in bronchitis patients.  Since this article was published recently, I think there will potentially be more research with anti-inflammatories, antibiotics and the effect they have on bronchitis.

Source:
Efficacy of Anti-inflammatory or Antibiotic Treatment in Patients with Non-complicated Acute Bronchitis and Discoloured Sputum: Randomised Placebo Controlled Trial. BMJ, 4 Oct. 2013. Web. 08 Dec. 2013. <http://www.bmj.com/content/347/bmj.f5762.pdf+html>.

               

ZORVOLEX, a nonsteroidal anti-inflammatory drug

As a treatment for patients with acute pain, nonsteroidal anti-inflammatory drugs (NSAID) have been used.  However, the prescription of NSAIDs has been associated with cardiovascular and gastrointestinal risks.  

Iroko Pharmaceuticals announced recently the FDA approved the capsule ZORVOLEX.    ZORVOLEX is a nonsteroidal anti-inflammatory drug used to treat mild to moderate acute pain in adults.  ZORVOLEX is the first and only NSAID using SoluMatrix Fine Particle Technology.  Using this technology, ZORVOLEX contains diclofenac, which reduces the particle sizes 20 times.  This reduction in size, increases the surface area, and contributes to faster dissolution. The effectiveness was analyzed using a study of 428 patients, ages 18 to 65 whom had moderate to severe pain.  The patients were randomly divided into three groups with three different forms of treatment.  The groups included ZORVOLEX 35 mg 3 times a day, ZORVOLEX 18 mg 3 times a day, and placebo.  The patients treated with ZORVOLEX, 35 mg and 18 mg, reported significantly greater pain relief compared with patients receiving the placebo.  

The FDA has approved ZORVOLEX at the lowest possible effective dosage.  The FDA also recommends ZORVOLEX be used by patients for the shortest amount of time.  This is due to the cardiovascular and gastrointestinal risks involved with a high dosage of NSAIDs, which includes cardiovascular thrombotic events, myocardial infarction, stroke, gastrointestinal ulcers, gastrointestinal bleeds, and acute renal failure.  

It is encouraging to know that a low-dose nonsteroidal anti-inflammatory drug has been approved by the FDA and is available for physicians to prescribe to patients with acute pain.  However, it is important for acute pain patients to carefully get prescribed a low dose of ZORVOLEX due to the risks associated with a high dose of NSAIDs.

Source:  

"Introducing ZORVOLEX™ (diclofenac), the First Lower-Dose NSAID Developed Using SoluMatrix Fine Particle Technology™."  Pharmacy Times, 12 Nov. 2013. Web. 08 Dec. 2013. <http://www.pharmacytimes.com/publications/issue/2013/November2013/R613_November2013>.