Inflammation, Alzheimer's and polypharmacy

Hi everyone:

The last couple of topics have covered some areas of research that I help with at UA, so I thought it would be interesting to blog about them. 

 We study the neurological control of upper respiratory muscles in healthy individuals as well as certain disease states. As a primary clinical interest we want to investigate the pathophysiology of obstructive sleep apnea (OSA), since there are several other severe, multi-system complications that can arise from OSA including metabolic issues, cardiovascular problems and neurological dysfunction, either arising from a lack of proper sleep architecture or improper oxygenation. OSA is more common in obese individuals, but not exclusively. People with underlying neurological or psychological conditions are at a greater risk, as well as menopausal women.

For awhile we were studying the respiratory muscle functions of a man with Parkinson's Disease (PD) that was being treated for it using a deep-brain stimulator. We were able to turn off his stimulator for the trials, and the difference in symptom manifestation was remarkable. His tremors literally would start and stop like a switch was being flipped. He said that the therapy had changed his life, though it wasn’t perfect. He was willing to trade infrequent nausea for the ability to eat a bowl of cereal on his own or to tie his shoes without help.

 Deep brain stimulation, also known as a "brain pacemaker," has been used for quite some time, though the underlying mechanisms of function are unclear. Anytime we hear that kind of description for a therapy, we want to try and investigate possible side effects, particularly respiratory side effects. We were getting inconclusive and inconsistent recordings from our PD patient, and eventually noticed that he was dozing in and out while we were taking muscle recordings. This is a very common sign of poor sleep, and because of the patient's age we figured he hadn't been pulling any all-nighters or drinking huge amounts of caffeine like a college student, so we started trying to get some background information on his sleep history.

 He claimed that he actually slept fairly well, but that his wife complained about his snoring. Snoring is generally an indicator of OSA, so we got some more information. He had been taking Requip, which is a drug used to treat Restless Leg Syndrome. RLS is a condition commonly associated with PD, though some researchers question whether or not it is actually a unique condition or a manifestation of other disease conditions. Some ongoing research suggests that pharmacological treatment of RLS can exacerbate the condition for people with PD, and other research has demonstrated a potential link between RLS and sleep apnea. He also was taking preventative Aspirin therapy, and occasionally took sleep aids because he felt tired during the day. At this point we realized that we weren't going to be able to use this guy as a subject, because there were so many things potentially interfering with his respiratory cycle.

 I found it very interesting that “polypharmacy” had been associated with other inflammation state treatments, since we potentially ran into this problem doing neurophysiology research. Consideration of these neurologic conditions as inflammation states is a promising step towards furthering our neurophysiological research.

 http://www.mayoclinic.com/health/restless-legs-syndrome/DS00191

http://restless-legs-syndrome.emedtv.com/requip/requip-side-effects.html

http://www.ninds.nih.gov/disorders/deep_brain_stimulation/deep_brain_stimulation.htm

Probiotics and Clinical Disease

A few weeks ago, I went to an interesting lecture entitled, “Bacterial Colonization, Probiotics, and Clinical Disease” given by Allan Walker. The lecture focused on the hygiene hypothesis and the colonization of gut bacteria in children. Dr. Walker pointed that the colonization of bacteria in a person’s body occurs in four steps after leaving the germ-free in utero environment. The first exposure to bacteria is from a person’s mother while leaving the birth canal, the second round of exposure arises from oral feeding, the third from weaning, and the fourth phase is complete around the age of 2 years when the baby has complete adult colonization. Breast feeding and normal vaginal birth both help promote this bacterial colonization and can help against abnormal colonization that may lead to increased susceptibility to pathogens and immune mediated disease. It is apparent that a disruption in any of these steps may lead to a disruption in bacterial exposure during childhood development.

He highlighted many previous studies that have demonstrated the relationship between bacterial colonization and clinical disease. For example a study in Japan demonstrated that antibiotic use during infancy promotes a shift in the Th1/Th2 balance towards a Th2 dominant immunity in mice[1]. He also highlighted the importance of breast milk in promoting a normal pH and presence of normal intestinal flora. He argued that bacterial colonization helps promote a health host defense and that imbalances in T helper cells may lead to disease.

Through his description of countless studies that have examined the relationship of innate immunity and the presence of old friends, I was most interested in his research in probiotic treatment for clinical disease. He discussed that it may be possible to address the hygiene hypothesis by using probiotics as a surrogate for initial colonization and therapy for prevention and treatment of microbial-induced disease. I did not have much knowledge about probiotics but a simple google search yielded over two million matches, so it seems that they are certainly a hot topic. Probiotics are viable microbial dietary supplements used in fermented foods like yogurt and they claim to enhance natural defenses and prevent disease. You can by these in capsules in the supplement aisle and there are many dairy products that tout their probiotic qualities (such as Activia). Studies have shown that oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants[2]. However, clinical recommendations for probiotics are very much in the early stages, and Walker’s final conclusions stated that although probiotics may be a useful tool, many additional studies should be conducted to understand the specific function in clinical treatment.

[1] J Allergy Clin Immunol. 2001; 107(1):153-9
[2] Pediatrics 2005; 115; 1-4

For those of you interested in background of Probiotics
http://www.mayoclinic.com/health/probiotics/AN00389
http://www.msnbc.msn.com/id/27454348/ (mainstream article on MSNBC on probiotics in the news)
http://en.wikipedia.org/wiki/Probiotic (I know this is wiki, but it had an interesting history of their use, take it as a wiki source)

I addition I have the biliography from the lecture. If you are interested, let me know and I can scan/e-mail to you.

Acupuncture

I read the article titled The Neuroimmune Basis of Anti-inflammatory Acupuncture. I thought it would be helpful to blog about acupuncture and some of the theories behind its effects on the body.

HISTORY

Acupuncture originated in China and can be traced back to the Stone Age. At this time instead of needles sharp stones were used. As mentioned in the article the 5000-year-old mummy, Otzi, found in the Alps is thought to be further evidence of the use of acupuncture in ancient times. On his body there are over 50 tattoos that mark the locations of acupuncture points on his body.

Despite these ancient roots in Chinese history, acupuncture and other folk medicine declined during the Revolution of China in 1911. Yet during the Long March many of the soldiers used acupuncture to maintain the health of the People's Liberation Army. With the success of acupuncture in this situation, Mao Zedong, the leader of the Chinese Communist Party, became an advocate for the use of acupuncture on a larger scale. This seems very opposite of the rest of the party who criticized the use of folk medicine as a step backwards.

From this support, Traditional Chinese Medicine was born. Traditional Chinese Medicine is the formalized system of folk medicine that was taught in medical schools throughout China. It is still an important part of Chinese medical curriculum today.

Acupuncture was first brought over to the US in the 1970s. Travelers to China were fascinated by the use of acupuncture as the only anesthesia for patients during surgery. The National Acupuncture Association (NAA) was started during this time. The NAA hosted a number of seminars and research presentations around the US in order to increase acupuncture's popularity. It succeeded and in 1972 the first acupuncture clinic was opened in Washington, D.C.

METHODS

The basis of acupuncture is rooted in the belief that there is a substance within our bodies called Qi. This vital energy runs freely through our body along meridians. When an imbalance, or blockage of our Qi occurs, that is when acupuncture needs to be done. Acupuncture allows for drainage of excess Qi from certain areas, clearing of blockages, and promoting flow where stagnation has occurred.

When acupuncture is done, it is done along the meridians in the body. The twelve primary meridians in the body, or mai, correspond to the systems of function. These primary meridians are: Lung, Large Intestine, Stomach, Spleen, Heart, Small Intestine, Bladder, Kidney, Pericardium, San Jiao (not really associated with a specific body part, it is for the control of temperature), Gall Bladder, and Liver. There are also Eight Extraordinary Pathways, the Luo Vessels, the Divergents, and the Sinew Channels that are also used, just not as commonly.

In clinical practice a disposable stainless steel needle is usually used. The needle has a diameter between .18mm to .51 mm depending on the location. The ends of the needle is wrapped with wire or covered in plastic to stiffen the needle and allow it to be easily grasped by the acupuncturist. The length of the needle, and the depth it is inserted, depends on the style that the acupuncturist is using as well as what he is trying to alleviate.

With acupuncture heat or electricity can be applied to the area in order to further the affects of the needle. When heat is applied is usually done via moxibustion, which is the burning of herbs (usually mugwort). Moxibustion can be done several different ways. One way involves attaching the herbs to the exposed end of the needle and lighting it on fire. Another technique is holding a light stick of mugwort near the acupuncture needle. Another is applying an ointment to the area of the skin and then lighting the mugwort directly on the skin before inserting the acupuncture needle.

THEORIES


The two theories that are mentioned in the article that I felt weren't really explained clearly are the Gate-Control Theory and the DNIC theory. I wanted to share the information I found when I looked them up. This helped me out so I thought it might be helpful to others.

Gate-Control Theory

The Gate-Control Theory of Pain was proposed by Ronald Melzack and Patrick Wall in 1962 and in 1965. The theory states that pain is not just determined by the action of nociceptors. Nociceptors are receptors that take in a stimulus and cause us to perceive pain due to this stimulus. Yet Melzack and Wall state that there are other fibers that can affect this transmission of stimulus into pain. They state there are other nonnociceptive fibers that interact with the nociceptor fibers. Thus if these other fibers are stimulated they can actually counter the pain signal of the nociceptors.

This can be applied to acupuncture very easily. When applied to acupuncture this theory is saying that the insertion of the needle is actually activating nonnociceptive fibers in that area. This activation then causes a signal to be sent, which interferes with the nociceptors and the pain that is perceived is lessened.



DNIC

This stands for Diffuse Noxious Inhibitory Control. This theory seemed pretty complicated to me, so my explanation is only what I got from the information I found. I kind of simplified it down so I could easily understand it.

This idea is very similar to that of the Gate-Control Theory of Pain. It states that if you have a stimulus that is perceived as pain in a certain area, you can inhibit this by administering a painful stimulus in a distal area. This is like the general idea that if your head hurts and someone stands on your foot you won't head won't hurt anymore.


LINKS
Here is a link to an interactive map of the acupuncture points and meridians:
http://www.yinyanghouse.com/acupuncturepoints/locations_theory_and_clinical_applications


Here is a link to the NIH Conference statement that is mentioned in the article:
http://consensus.nih.gov/1997/1997Acupuncture107html.htm


Here is where I got some of the information about DNIC:
http://www.clas.ufl.edu/jur/200611/papers/paper_lovell.html

Aspirin and Myocardial Infarctions

Everyone has seen the commerical where the man takes apsirin to stop his heart attack...well that got me thinking...is it true? How does it work?

In October 1997, the AHA reported in its journal, Circulation, that up to 10,000 more people would survive heart attacks if they would chew one 325 milligram aspirin tablet when they first had chest pain or other sign of a heart attack. Other studies have come to similar conclusions. One found that heart attack patients who took aspirin when their symptoms began, and then daily for one month, significantly lowered their risk of dying and of having another heart attack or stroke over the people in the study who were given the placebo. Now, just about all researchers agree that patients should be given aspirin during the first hour -- during pre-hospital transport or in the Emergency Room -- if a heart attack is suspected.

How it works: The Basics:

Basically, it interferes with the production of a series of chemicals in the body -- called prostaglandins -- that regulate many of the body’s vital functions. By blocking certain prostaglandins, aspirin lowers body temperature, relieves minor aches and pains, relieves inflammation and interferes with the role of blood platelets in forming clots. It is this last effect that appears to impact on risk for heart disease. Blood clots are formed by platelets grouping together. Aspirin interferes with this process by making the platelets less “sticky” -- and therefore less successful in grouping together -- by inhibiting the manufacture of prostaglandins. This same blood “thinning” action that makes aspirin effective in reducing a person’s risk for heart disease, but “you have to chew the aspirin, especially if you only have enteric-coated aspirin, because if you just pop one of those, you won’t see any action for hours.” Always call 911 first. Then, after chewing the aspirin, you can wash it down with water and get immediate medical attention.

Interesting Facts:

Aspirin was officially introduced 100 years ago and has been marketed in its current form for more than 80 years.
The origin of the drug can be traced back to Hippocrates. he advised his followers to chew the leaves of the willow tree to alleviate pain.
The Chinese have been using the bark of the same trees -- which contain salicin -- to control fever.
In the early 1800’s different derivatives of this bark were tested and one -- acetylsalicylic acid, the chemical name for aspirin -- was found to be tolerated better than the others.

http://www.yourfamilyshealth.com/cardiology/aspirin/

Alternative Medicine: Cupping

The review article, The Neuroimmune Basis of Anti–inflammatory Acupuncture, mentions the term “cupping”. As I had mentioned before in class, I grew up with Russian gymnastic coaches who brought their knowledge of Eastern Medicine to the West. I was lucky enough not to get stung by bees but had the enjoyment of having cupping done. Hope you find it as interesting as I did.

Illness is caused by an imbalanced, stagnated or weak Qi. Acupuncturists are trained to use cupping when Qi needs to be drawn to the surface of the body from deep within. The cups are applied to acupuncture points. Cupping is a technique in which glass cups are heated from the inside with fire to create a vacuum and then placed on the afflicted area of the body. The cup's suction pulls at the skin and is said to "suck out" the body's toxins.

Sources of these toxins include: air pollution, drugs, junk food, and smoking, waste products of metabolism, trauma/accidents, stress, anger, anxiety and depression. Toxins can slow down or block supply of blood that delivers much needed oxygen, nutrients, water, mineral electrolyte, vitamins, enzymes, hormones and immune system cells to cells, tissues and organs. This also prevents the removal of metabolic waste products and toxic substances which are excreted through our lungs, skin and urine. As a result, our cells, tissues, and organs become progressively weak, inefficient, and easily overcome. This can cause tissue/organ malfunction and infection to take place. This will cause symptoms of diseases such as aches and pain, numbness, fever, cough, stomach ache, constipation, diarrhea and headaches. If left untreated, further accumulation of toxic waste may lead to serious chronic diseases including hypertension, ulcers, diabetes, arthritis, Alzheimer disease, migraine, heart disease, stroke and cancer.

There are 3 different cupping techniques.

1. Air Cupping: most common, no side effects, prevents and treats slight ailments
2. Aggressive Cupping: used for serious chronic diseases, marks may remain up to 1 year
3. Blood Cupping: cups applied to scratched skin, toxic blood is removed

Some diseases treated by Cupping Therapy

• cold/cough
• headaches/migraine
• asthma
• allergies
• hypertension/hypotension
• osteoarthritis
• rheumatoid arthritis
• diabetes
• kidney/liver problems
• Alzheimer’s disease
• stroke
• cancer

Interestingly, if the person is really healthy, the redness will dissipate very quickly with the skin returning to its normal color, usually within minutes or hours. However, if the person is in poor health, injured or experiencing Qi blockages, there will be some bruising and skin will not return to normal color for a couple of days rather than hours.

http://www.bestcuppingtreatment.com/page/1069270