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bbc
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Date Joined Mar 2008
Total Posts : 1580
   Posted 12/31/2008 10:44 AM (GMT -6)   

Scientists Successfully Treat New Mouse Model Of Inflammatory Bowel Disease

Researchers trying to improve cancer immune therapy have made an unexpected find: They've produced the most accurate mouse model to date of inflammatory bowel disease (IBD), a cluster of conditions that afflict approximately 1.4 million Americans with abdominal pain, constipation and diarrhea.

The two most common forms of IBD are Crohn's disease and ulcerative colitis (UC); in extreme cases, they can be fatal. The mouse model closely resembles the most serious form of human UC and is uniformly fatal. But scientists successfully treated the mice with a pair of broad spectrum antibiotics, easing gut inflammation and increasing survival. The results, reported this week in Public Library of Science Medicine, have researchers eager to follow up both in the clinic and the lab.

"The antibiotics we gave the mice were used individually in unsuccessful clinical trials as ulcerative colitis treatments, but now we have colleagues who are thinking of giving combined therapy an informal try," says co-senior author Thaddeus S. Stappenbeck, M.D., Ph.D., assistant professor of pathology and immunology and of developmental biology. "The antibiotics probably won't be a cure by themselves, but they may provide us with a potent new approach to combine with other therapies."

The mice may also allow scientists to learn which species of gut microorganisms are becoming embroiled in battles with host immune systems, triggering the symptoms of UC. That information could allow the development of stronger and more specific treatments.

Silvia Kang, a former graduate student in the laboratory of co-senior author Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, created the mouse model by crossbreeding two mouse lines they had developed for cancer immune therapy research. Each mouse line had one protein knocked out that restrained immune T cells from shifting into attack mode.

"The idea was to see if we could create super killer T cells we could use to attack tumors," says Allen. "But all the mice became sick early on, started to lose weight and we soon realized that they all had serious gastrointestinal issues."

Allen decided to consult with Stappenbeck, an expert in IBD.

"I've looked at quite a few proposed mouse models of IBD, and I recognized right away that this had the potential to be outstanding," says Stappenbeck. "The colons of the mice were incredible. They were filled with inflammatory T cells. We found the mice almost exactly replicated the most acute types of ulcerative colitis."

Unlike prior models of IBD, the mice consistently develop gastrointestinal problems within a short time period and at a predictable point in their lifespan. When researchers treated the mice at three weeks with the antibiotics ciprofloxacin and metronidazole, colon inflammation was reduced and the mice were able to gain weight and survive longer.

Scientists believe IBD results from the host immune system damaging the tissues of the gut while erroneously attacking food and gut microorganisms that aid food digestion. There are an estimated 500 different species of microbes living in the gut, so sorting out which species are being attacked by the immune system has been an imposing challenge.

The new model may significantly ease that challenge. Although the dual antibiotics used to treat the mice are broad-spectrum, they didn't sterilize the guts of the mice, suggesting that the treatment happened to eliminate the microorganisms causing IBD.

"We'd like to treat the mice and then reintroduce candidate microorganisms into their guts to see if this restarts the inflammatory reaction," says Stappenbeck.

Stappenbeck and Allen plan continued collaborative study of the model.

Kang SS, Bloom SM, Norian LA, Geske MJ, Flaveli RA, Stappenbeck TS, Allen PM. An antibiotic-responsive mouse model of fulminant ulcerative colitis. Public Library of Science Medicine, March 3, 2008.

Funding from the National Institutes of Health and the Cancer Research Institute supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University in St. Louis
One Brookings Dr., Campus Box 1070
St. Louis, MO 63130
United States
http://www.wustl.edu

Source: WUSTL
Country of Origin: US
Date originally Published: 7-Mar-08
Date added to Accessibility: 11-Mar-08


Moderate Pancolitis
Dx'd 05/2007
7 Pentasa per day (4/3)
Corti Foam p.m. 2X per week
Prebiotics and Probiotics, Bowel Soother, Fish Oil, Calcium, Multi Vitamin and Melatonin
Trying to reduce sugar in my diet but cannot tolerate artificial sweetners
I excersice daily
Did I happen to mention I HATE this disease!!!

Post Edited (bbc) : 12/31/2008 12:37:18 PM (GMT-7)


crazytrain411
Regular Member


Date Joined Nov 2008
Total Posts : 109
   Posted 12/31/2008 1:18 PM (GMT -6)   
cant see the link bbc.
I also wonder what they plan with anti-biotics when it seems to make things worse for us.
Off of 5-ASA (6 years) and 1-day minor flareup since probiotics started.

Probiotics 18 strains (vsl#3 + N.F. Ultimate multi probiotic + Trophic Acidophilus Plus + Nature's Way P. Reuteri + Florastore S. Boulardii) - 500 billion per day. No sugar, Oatmeal in the morning.
L-glutamine, elm powder, vit b & folic acid, 5 g vitamin C, vit D, vit E, Calcium+Magnesium


bbc
Veteran Member


Date Joined Mar 2008
Total Posts : 1580
   Posted 12/31/2008 1:40 PM (GMT -6)   
crazytrain

I was thinking the same thing about the antibiotics but then I thought about it and realized that they make snake bite antidote from snake venom...hmmm
Moderate Pancolitis
Dx'd 05/2007
7 Pentasa per day (4/3)
Corti Foam p.m. 2X per week
Prebiotics and Probiotics, Bowel Soother, Fish Oil, Calcium, Multi Vitamin and Melatonin
Trying to reduce sugar in my diet but cannot tolerate artificial sweetners
I excersice daily
Did I happen to mention I HATE this disease!!!


mudua
Regular Member


Date Joined Apr 2007
Total Posts : 459
   Posted 12/31/2008 1:43 PM (GMT -6)   
crazytrain411 said...
cant see the link bbc.
I also wonder what they plan with anti-biotics when it seems to make things worse for us.

  http://www.medicalnewstoday.com/articles/99815.php

bbc
Veteran Member


Date Joined Mar 2008
Total Posts : 1580
   Posted 12/31/2008 1:46 PM (GMT -6)   
I would encourage everyone to read the entire article, as it makes terrifc amounts of sense and it is new research (Spring 2008).

Wouldn't it be wonderful if 2009 was the year for a breakthrough in UC treatment : )))
 
I called and left a msg for Professor Strappenbeck to see what has occured since March and if they were able to reintroduce the micro-organisms to see if it restarted the inflammitory reaction...I hope he calls back.


Moderate Pancolitis
Dx'd 05/2007
7 Pentasa per day (4/3)
Corti Foam p.m. 2X per week
Prebiotics and Probiotics, Bowel Soother, Fish Oil, Calcium, Multi Vitamin and Melatonin
Trying to reduce sugar in my diet but cannot tolerate artificial sweetners
I excersice daily
Did I happen to mention I HATE this disease!!!

Post Edited (bbc) : 12/31/2008 1:03:21 PM (GMT-7)


Christine1946
Veteran Member


Date Joined Aug 2008
Total Posts : 5962
   Posted 12/31/2008 1:58 PM (GMT -6)   
     I didn't think UC was fatal!
62 yr old granny. South Jersey
Diagnosed with ulcerative proctitis in 1998 in hospital
Hospitalized (2nd time) in May 2008
Update 11/03/08...finally in remission!!  Hope I don't jinx myself.  Off the prednisone since 11/01/08...now see if I can stay off for longer than two weeks.  Other meds: 6MP (75 mgm), colazal (6 per day), Benicar and Toprol (high blood pressure meds), Probiotic (2 per day), fish oil capsule and multi-vitamin and calcium with vitamin D.


bbc
Veteran Member


Date Joined Mar 2008
Total Posts : 1580
   Posted 12/31/2008 2:07 PM (GMT -6)   
Toxic magacolon left untreated can be the end, as could hemmoraging etc and I'd imagine if one left the gut untreated with sverve UC you would die overtime from lack of nutrion, blood loss etc etc
What in the article got you thinking about it...what it this? the mice were able to gain weight and survive longer.

Christine1946 said...
     I didn't think UC was fatal!


Moderate Pancolitis
Dx'd 05/2007
7 Pentasa per day (4/3)
Corti Foam p.m. 2X per week
Prebiotics and Probiotics, Bowel Soother, Fish Oil, Calcium, Multi Vitamin and Melatonin
Trying to reduce sugar in my diet but cannot tolerate artificial sweetners
I excersice daily
Did I happen to mention I HATE this disease!!!


Sara14
Veteran Member


Date Joined Mar 2007
Total Posts : 4157
   Posted 12/31/2008 3:06 PM (GMT -6)   
Probably this, bbc: "The two most common forms of IBD are Crohn's disease and ulcerative colitis (UC); in extreme cases, they can be fatal." (Second paragraph)

Thanks for posting.
Diagnosed with UC March 2007; Asacol 4 tablets 3x/day; Rowasa; Canasa; Viactiv; Metamucil wafers; multivitamin; sublingual allergy drops


bbc
Veteran Member


Date Joined Mar 2008
Total Posts : 1580
   Posted 12/31/2008 4:02 PM (GMT -6)   
Thanks sara and you're welcome.
Moderate Pancolitis
Dx'd 05/2007
7 Pentasa per day (4/3)
Corti Foam p.m. 2X per week
Prebiotics and Probiotics, Bowel Soother, Fish Oil, Calcium, Multi Vitamin and Melatonin
Trying to reduce sugar in my diet but cannot tolerate artificial sweetners
I excersice daily
Did I happen to mention I HATE this disease!!!

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