Monday, February 25, 2013

Researchers Report - 200 Genes Have a Connection to Crohn's Disease

Wish there was more to be said about these 200 genes they found that point to Crohn's.  Nice to know.  

Crohn's Disease, from what I read on a regular basis, is one of the most complex diseases to understand.  Scientists seem to always discover a relationship with "A" ("A" could be any of the following, I'm only listing a few:  impaired  immune response, an increased level of a serine protease, an antigen/toxin, introduced into the body,  a pathogen {a bacteria(especially MAP), virus, fungus} are associated with Crohn's, genetic factors... 200 of them apparently, drugs ( Accutane is the one I hear about the most), environmental factors such as hormonal therapy, ex. birth control.  Not enough exposure to parasites, microorganisms and infectious agents in early childhood- See: Hygiene Hypothesis.     OK that's enough.    You get the point.  

Crohn's can be associated with so many factors, but the progression to determine more components about that factor "A", may lead to other discoveries that bring understanding about how "A" and "B", but not enough to progress with more research studies. 

Then ... That's it!  Scientists reach dead ends. It seems as if the findings discovered do not provide enough concrete information to bring more understanding about the disease which halts additional  research You never hear  much more about the relationship between A & B again. This happens so much with so many of the studies that seek to understand the disease and they all seem to reach a dead end at some point during the research.  There's  a few factors that have a pretty good progression that continue to lead to more connections; & its MAP.  It is the only information that I have read  and continue to read that discover  new findings and links to Crohn's.  Scientists are able to get somewhere with their findings that allow them to be able to do more studies and they gain more  understanding about the disease. 

The other factor that stands out is the Hygiene Hypothesis.  Read about it, it makes sense. 

Of all the conditions we would have to have is one as complicated as the Crohn.    I associate the Crohn's with a nightmare person that is sorta like a stalker/rude/unpredictable/enjoys messing up my day(s) and overstays their welcome ... but they were never welocome to begin with ... The nightmare just comes right in and makes itself at home.   

Anyway... enough of my babble.  Feel free to comment on your thoughts on what research seems to stand and  make progress toward an effective treatment and maybe even a cure.  I'd love to hear what you've found .




WEDNESDAY, Dec. 19 (HealthDay News) -- Using a new technique, researchers have pinpointed a large number of additional genes associated with Crohn's disease, bringing the total to 200.
The scientists at University College London, in England, created a new method to identify and map the locations of genes associated with complex inherited diseases such as Crohn's.
Crohn's disease, a type of inflammatory bowel disease, affects about 100 to 150 people out of every 100,000. Understanding more about the genes associated with the disease may lead to improved treatments, the researchers said.
HealthDay news imageThe 200 genes so far linked to Crohn's are more than have been found for any other disease, according to the researchers. For example, just 66 gene regions are known for type 2 diabetes.
"The discovery of so many gene locations for Crohn's disease is an important step forward in understanding the disease, which has a very complicated genetic basis," study senior author Dr. Nikolas Maniatis said in a university news release. "We hope that the method we have used here can be used to identify the genes involved in other diseases which are similarly complex -- for example different cancers and diabetes."
The new research was published Dec. 13 in the American Journal of Human Genetics.
SOURCE: University College London, news release, Dec. 13, 2012
HealthDay

Thursday, February 14, 2013

#LDN as treatment- 4 #Fibromyalgia - Positive Results in Trial

Published in February 2013, study to determine the effectiveness of naltrexone in low doses for fibromyalgia has again displayed positive results as a good treatment option for this condition.  Low Dose Naltrexone showed significant reduction in baseline pain, improvement with general quality of life and also mood improvement.  

Abstract of study is below.


Low-dose naltrexone for the treatment of fibromyalgia: Findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.



 2013 Feb;65(2):529-38. doi: 10.1002/art.37734.

Younger J, Noor N, McCue R, Mackey S.

Source

Stanford University School of Medicine, Palo Alto, California. jarred.younger@stanford.edu.

Abstract

OBJECTIVE:

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.

METHODS:

Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.

RESULTS:

When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.

CONCLUSION:

The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication.
Copyright © 2013 by the American College of Rheumatology.
PMID:
 
23359310
 
[PubMed - in process]

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Low-dose naltrexone for the treatment of fib... [Arthritis Rheum. 2013] - PubMed - NCBI:

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Tuesday, February 12, 2013

*Videos* - Interview w/ Dr. Bihari about LDN - History of LDN

Want to know about LDN ....or  should I say.. Do you want to know MORE about LDN.?  By now, you should know the basics and then some if you have been reading my blogs that I've posted  about the treatment 

If you haven't watched anything or read anything about LDN, this is the one to watch. The doctor  answers a lot of questions and talks about how the drug works.  You'll understand it.   

Harvard-educated Bernard Bihari, MD is interviewed about his life, and his discovery of Low Dose Naltrexone (LDN) for autoimmune diseases: multiple sclerosis, lupus, rheumatoid arthritis, Crohn's disease; also HIV/AIDS and some cancers. This video was given to me by Dr. Bihari's widow, Jacqueline Young.

The video is below.  The interviewer isn't that great cause you can't hear him to well.  Despite that, the Dr. is easy to understand and follow.   This is a long video  (fyi), not all may be interested if you don't care about knowing how the drug works to treat different diseases .  I watched the whole thing because I like such action packed videos.  lol  Im such a nerd!  
I wanted to hear what the man had to say about his advancements  that he discovered through his lifetime.  He's freaking awesome.  He speaks a lot about the research he was working on before he passed away which was HIV/AIDS and cancer and how LDN really is helpful with regulating the immune system .  But he's talking about the body and how the endorphins in the body effect the immune system/response.  He touches on the following points that you may be interested in watching 
I'm glad I watched this because I have a better understanding of how the medicine works in the body and helps balance/regulate the immune system.  His theory suggests that people with cancer, aids, autoimmune diseases have a lower than normal amt of endorphins in the body.  Its all about increasing the body's endorphins!
11:40 - talks about the improvement in AIDS patients with taking ldn, also talks about cancer patients
16:10 - He speaks about LDN and the endorphins. 
18:45 - cell death (cancer cells)caused by endorphins 
**20:19 - 23:00 ** I would def watch this part.  good explaining about the importance of endorphins more about how ldn works in the body (cancer patients... speaks about low endorphins  and how LDN raises the level of endorphins in the body) 
51:10 - the different endorphin receptors and what they effect in the body. interesting 
 He says around 30K-40K people take LDN.  

& Here it is...LISTEN --->  57:09 - 100:20 Touches on Autoimmune Diseases FINALLY.  My undertsanding of how this works goes like this I think.    -   .our t-helper cells get out of wack and get impaired  some how... (probably by a bacteria,  that throws it off) that therefore effects our killer cells & macrophages which get confused with the self vs the bacteria/fungus.  They get confused and attack own tissue/cells and not the foreign bacteria.  From what he says I think the LDN enhances the functioing of the t-cells by increasing the endorphin levels, the endorphins then regulate immune response
101:13 - the amount it costs to run clinical trials for LDN for each condition.  not sure if  he said 15 or 50 million for the 1st 3 trials.  He says that finding a drug company that would want to run the trials,  work w/ FDA, ability to manufacturer , distribute and then advertise is difficult.  
1:04:40 -  talked about low toxicity rate... it doesn't exist.  That's so bomb!, the cost (super cheap)..  Those aspects are probably the main reason LDN will never get approved to treat any other condition..  There's no money to make with this medicine, what would be the incentive.... to make people better... Yeah ok!! LOL  Guess doctors will just have to continue to write it as "off label use".  


Background of Low Dose Naltrexone LDN


Naltrexone was licensed in 1984 by the FDA in a 50 mg dose as a treatment for heroin addiction. It is a pure opiate antagonist (blocking agent) and its purpose was to block the opioid receptors that heroin acts on in the brain. When it was licensed, Dr. Bihari, then involved in running programs for treating addiction, tried it in more than 50 heroin addicts who had stopped heroin use. None of the patients would stay on the drug because of side effects experienced at 50 mg such as insomnia, depression, irritability and loss of feelings of pleasure, all due to the effect of the drug at this dose in blocking endorphins. These are the hormones in the body that heroin resembles. Physicians treating heroin addicts therefore, for the most part, stopped prescribing naltrexone. In 1985, a large number of heroin addicts began to get sick with AIDS—studies showed that 50% of heroin addicts were HIV Positive.
Dr. Bihari and his colleagues decided to shift their research focus to AIDS, in particular focusing on ways of strengthening the immune system. Since endorphins are the hormones centrally involved in supporting and regulating the immune system, levels of endorphins were measured in the blood of AIDS patients. They were found to average only 25% of normal.
Naltrexone, when given to mice and people at high doses, raises endorphin levels in the body's effort to overcome the naltrexone blockade. This drug became the focus of Dr. Bihari's research group. When the group discovered that endorphins are almost all produced in the middle of the night, between 2 AM and 4 AM, the studies focused on small doses (1.5-4.5 mg at bedtime) with the hope that a brief period of endorphin blockade before 2 AM might induce an increase in the body's endorphin production. In fact, the drug did so in this dosage range. It had no effect below 1.5 mg and too much endorphin blockade at doses over 5 mg. A placebo-controlled trial in AIDS patients showed a markedly better outcome in patients on the drug as compared with those on placebo.
During the trial, a close friend of Dr. Bihari's daughter had three acute episodes of multiple sclerosis over a nine-month period with complete spontaneous recovery from each. Because of his knowledge of MS as a neurologist and of recent evidence of an autoimmune component in the disease, Dr. Bihari started his daughter's friend on naltrexone at 3 mg every night at bedtime. She took it for five years with no further attacks. At that point, when a particular month's supply ran out, she stopped it because of some denial that she had MS. Three and a half weeks later, she developed an episode of weakness, numbness, stiffness and spasms in her left arm and resumed LDN, which she has stayed on since. This episode cleared and over the 12 years since, she has had no further disease activity.
The apparent mechanism of action of LDN in this disease parallels that in AIDS and other immune-related diseases. A small dose of the drug taken nightly at bedtime doubles or triples the endorphin levels in the body all of the next day restoring levels to normal. Since endorphin levels are low in people with MS, immune function is poorly orchestrated with significant impairment of the normal immune supervisory function of CD4 cells. In the absence of normal orchestration of immune function, some of the immune system cells "forget" their genetically determined ability to distinguish between the body's 100,000 unique chemical structures (called "self") and the chemical structures of bacteria, fungi, parasites and cancer cells (called "non-self"). With this loss of immunologic memory, some cells begin to attack some of the body's unique chemical structures. In the case of people with MS, the tissue attacked by immune cells (particularly macrophages) is primarily the myelin that insulates nerve fibers. These attacks result in scars in the brain and spinal cord called plaques. LDN in such patients works by restoring endorphin levels to normal, thereby allowing the immune system to resume its normal supervision and orchestration.
There exists a common notion that the immune system in a person with an autoimmune disorder is too strong and, in its exuberance, targets a body tissue for attack. Rather, the evidence is more consistent with autoimmunity resulting from immunodeficiency.1 Kukreja et al have demonstrated that multiple immunoregulatory T cell defects lie behind Type 1 diabetes both in humans and in non-obese diabetic mice.2
Multiple scientific papers from various other research centers have demonstrated that an underlying immunodeficiency is characteristic of any tested autoimmune disease. Examples thus far reported include multiple sclerosis, rheumatoid arthritis, Crohn's disease, and chronic fatigue syndrome.3, 4, 5
Sacerdote et al measured low beta-endorphin levels in two animal examples of autoimmune disease — a mouse strain with a lupus-like syndrome and a strain of chicken with an autoimmune thyroiditis.6 They had significantly lower hypothalamic concentrations of the opioid than normal controls. In each case, the low levels of beta-endorphin were found well before the expression of autoimmune disease. This adds to considerable evidence of a key role for endorphins in regulating immune responses and suggests a therapeutic pathway.
Bihari et al found that a low oral dose of the opioid antagonist naltrexone, when taken at bedtime, led to a doubling or tripling of low levels of circulating beta-endorphin.7 Bihari has since treated some 100 people with autoimmune disorders. None of them has progressed further while the patient continued taking low dose naltrexone each night at bedtime. Since no side effects are apparently associated with its use, this medication might well be studied as a possible preventive for Type I diabetes in those youngsters with beta-cell autoantibodies.

Footnotes

  1. Buckley RH. Primary Immunodeficiency Diseases Due to Defects in Lymphocytes. N Engl J Med. 2000; 343:1313-1324.
  2. Kukreja A, Cost G, Marker J, et al. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest. 2002;109(1):131-40.
  3. Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P.Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. Ann N Y Acad Sci. Jun 2005;1051: 255-62.
  4. Marks DJ, Harbord MW, MacAllister R, Rahman FZ, Young J, Al-Lazikani B, Lees W, Novelli M, Bloom S, Segal AW. Defective acute inflammation in Crohn's disease: a clinical investigation. Lancet. Feb 2006;367 (9511): 668-78.
  5. Vernon SD, Reeves WC. The challenge of integrating disparate high-content data: epidemiological, clinical and laboratory data collected during an in-hospital study of chronic fatigue syndrome. Pharmacogenomics. Apr 2006;7 (3): 345-54.
  6. Sacerdote P, Lechner O, Sidman C, et al. Hypothalamic beta-endorphin concentrations are decreased in animals models of autoimmune disease. J Neuroimmunol. 1999;97(1-2):129-33.
  7. Bihari B, Drury FM, Ragone VP, et al. Low Dose Naltrexone in the Treatment of Acquired Immune Deficiency Syndrome. Oral Presentation at the IV International AIDS Conference, Stockholm, Jun 1988.
Dr. Skip Lenz at the 08 LDN Conference at USC, 

www.skipspharmacy.com - Very good Compounding Pharmacy for LDN

Video talks about taking other drugs with LDN (pain meds)


Dr. Lenz talks about patients' symptoms prior to taking LDN, after taking LDN & side-effects
 (aw poor guy. he said he only makes 32 cents/mo from the sales of LDN (fyi-he owns skips pharmacy..


He says about 4500 doctors write scripts for LDN in the US(these are just #'s at his pharmacy)
He mentions how many people w/ Crohns take LDN from his pharmacy, 200 I believe. and he called Crohnies amazing people.. hahaa Go to 1:33.  He mentions Crystal the chick w/ the list of all doctors that prescribes LDN across the US and many other countries.  She was very helpful to me when i was searching for a prescribing Dr. (If you'd like to know which doctors prescribe in your area, just let me know.  I will give you her contact info)  

Naltrexone is an opiate antagonist drug developed in the 1970s and approved by the FDA in 1984 for opiate and drug abuse treatment. When used at much lower doses in an off-label protocol referred to as low dose naltrexone (LDN), the drug has been shown to halt disease progression in Crohn's disease and certain cancers, to reduce symptoms in multiple sclerosis and autism, and to improve numerous autoimmune and neurodegenerative conditions, including Parkinson's disease and amyotrophic lateral sclerosis (ALS).
Grounded in clinical and scientific research, this book describes the history of naltrexone, its potential therapeutic uses, its effects on the immune system, its pharmacological properties, and how the drug is administered. It also lists fillers and compounding pharmacies, doctors who prescribe LDN, and patient resources, and includes interviews with LDN patients and researchers. *Author: Moore, Elaine A./ Wilkinson, Samantha/ Agrawal, Yash Pal *Binding Type: Paperback *Number of Pages: 213 *Publication Date: 2008/12/04 *Language: English *Dimensions: 8.80 x 5.90 x 0.70 inches


Blocking Tumor-Elicited Inflammation & The Impact on Cancer Growth

Interesting short article published in Nature.  It discusses how tumor-associated inflammatory reaction can lead to cancer, but what happens when this inflammatory response is disrupted, blocked, interrupted?  Something to think about.

Blocking Tumor-Induced Inflammation Impacts Cancer Development The findings are published in the October 3, 2012 Advanced Online Edition of Nature.


Oct. 3, 2012
 — Researchers at the University of California, San Diego School of Medicine report the discovery of microbial–dependent mechanisms through which some cancers mount an inflammatory response that fuels their development and growth.
The association between chronic inflammation and tumor development has long been known from the early work of German pathologist Rudolph Virchow. Harvard University pathologist Harold Dvorak later compared tumors with “wounds that never heal,” noting the similarities between normal inflammation processes that characterize wound- healing and tumorigenesis or tumor-formation.
Indeed, 15 to 20 percent of all cancers are preceded by chronic inflammation – a persistent immune response that can target both diseased and healthy tissues. Chronic hepatitis, for example, may result in hepatocellular carcinoma (liver cancer) and inflammatory bowel disease can eventually cause a form of colon cancer, known as colitis-associated cancer.


Still, most cancers are not preceded by chronic inflammation. On the other hand, they exploit ubiquitous, infiltrating immune cells to unduly provoke and hijack the host inflammatory reaction. Until now, the mechanism of so-called “tumor-elicited inflammation,” which is detected in most solid malignancies, was poorly explained.
A Mouse colorectal tumors display inflammatory infiltration by macrophages (green) and activated stromal cells (red). The question of why and how tumors recruit immune cells remains unknown. (Credit: UC San Diego School of Medicine) dd caption
“The tumor-associated inflammatory reaction is an emerging and vibrant field for biomedical studies. It may hold the keys for future preventive and therapeutic measures,” said first author Sergei Grivennikov, PhD, noting that studies of long-term users of non-steroidal anti-inflammatory drugs, such as aspirin, have revealed that general inhibition of inflammation reduces the risk of cancer death by up to 45 percent, depending on the type of cancer. “So inhibition of inflammation during cancer development may be beneficial.”
Studying early colonic tumors in humans and in animal models, the researchers, led by principal investigator Michael Karin, PhD, Distinguished Professor of Pharmacology and head of the Laboratory of Gene Regulation and Signal Transduction at UC San Diego, found that developing tumors disrupt tissue homeostasis (the normal, healthy functioning of tissues), in part because they lack a particular protective protein coating and a tight seal between their epithelial cells – a basic cell type that covers most internal surfaces and organs. Without that coating and the cellular seal, ordinarily benign, commensal bacteria present in the colon can enter the tumor to be recognized by immune cells as invaders, launching an inflammatory reaction.
In addition, said Grivennikov, who is a scientist in Karin’s lab, “cell-to-cell contacts are defective in tumors, further allowing entry of microbial products from the intestinal lumen into the tumor. These microbial products are recognized by tumor-associated macrophages and dendritic cells, which are normally isolated from commensal microflora by the intestinal barrier.”
In response, the immune cells produce signaling proteins called cytokines that further spur the inflammatory process. Chief among these is a cytokine called Interleukin-23, which regulates tumor-elicited inflammation and triggers the production of other inflammatory cytokines that promote tumor development and progression.
Grivennikov said that when researchers reduced the presence of commensal microflora through a combination of broad spectrum antibiotics, tumor-elicited inflammation and tumor growth were dampened.
“This is a very nice demonstration of how tumor-elicited inflammation in cancers that arise in the absence of underlying chronic inflammatory disease can be induced,” he said. “The next step is to look for the upregulation of Interleukin-23 and related cytokines in colon cancer patients, inhibit these cytokines and determine whether these impact cancer progression and response to therapy.”
Funding for this research came, in part, from the Crohn’s and Colitis Foundation of America, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K99-DK088589; UCSD DDRDC Pilot Grant DK080506; the Croucher Foundation and China Postdoctoral Science Foundation; the Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation; SPAR Austria; National Institutes of Health grants R01CA082223, A1043477 and DK035108 and the American Association for Cancer Research.
Co-authors include Kepeng Wang, UCSD Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology and the Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, China; Daniel Mucida, La Jolla Institute for Allergy and Immunology and the Laboratory of Mucosal Immunology, The Rockefeller University, New York; C. Andrew Stewart, Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bernd Schnabl, UCSD Department of Medicine, School of Medicine; Dominik Jauch and Guann-Yi Yu, UCSD Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology; Koji Taniguchi, UCSD Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology and Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo; Christoph H. Österreicher, UCSD Department of Medicine, School of Medicine and Institute of Pharmacology, Center for Physiology and Pharmacology Medical University of Vienna, Austria; Kenneth E. Hung, Department of Medicine, Tufts Medical Center, Boston; Christian Datz, Department of Internal Medicine, Oberndorf Hospital, Paracelsus Medical University Salzburg, Austria; Ying Feng and Eric R. Fearon, Departments of Internal Medicine, Human Genetics and Pathology, University of Michigan Medical School; Mohamed Oukka, Seattle Children’s Research Institute, Washington; Lino Tessarollo, Mouse Cancer Genetics Program, National Cancer Institute, National Institutes of Health; Vincenzo Coppola, Department of MVIMG, Ohio State University-CCC, Wexner Medical Center; Felix Yarovinsky, Department of Immunology, University of Texas Southwestern Medical Center; Hilde Cheroutre, La Jolla Institute for Allergy and Immunology; Lars Eckmann, UCSD Department of Medicine, School of Medicine; and Giorgio Trinchieri, Cancer and Inflammation Program, Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health.

Journal Reference:
  1. Sergei I. Grivennikov, Kepeng Wang, Daniel Mucida, C. Andrew Stewart, Bernd Schnabl, Dominik Jauch, Koji Taniguchi, Guann-Yi Yu, Christoph H. Österreicher, Kenneth E. Hung, Christian Datz, Ying Feng, Eric R. Fearon, Mohamed Oukka, Lino Tessarollo, Vincenzo Coppola, Felix Yarovinsky, Hilde Cheroutre, Lars Eckmann, Giorgio Trinchieri, Michael Karin. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growthNature, 2012; DOI:10.1038/nature11465