Re: Re: Interesting article: cystic fibrosis pig model

[Guest guest]

If I am understanding right, The fish oil or omega 3 or DHA (all the same thing) fixes the bile duct injury? Or prevents it from getting worse after the injury? Looks like PSCers should be taking fish oil!

Dave, are you in the medical field. Just curious.

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

Re: Interesting article: cystic fibrosis pig model

Hi Lori;They give the cystic fibrosis mutant mice oral dextran to induce colitis. This causes bile-duct injury closely resembling human PSC. The bile-duct injury is blocked by feeding the mice docosahexaenoic acid (DHA), an anti-inflammatory omega-3 fatty acid found at high levels in fish oil:Blanco PG, Zaman MM, Junaidi O, Sheth S, Yantiss RK, Nasser IA, Freedman SD 2004 Induction of colitis in cftr-/- mice results in bile duct injury. Am. J. Physiol. Gastrointest. Liver Physiol. 287: G491-G496. http://www.ncbi. nlm.nih.gov/ pubmed/15064232If you follow the link to the full paper, http://ajpgi. physiology. org/cgi/content/ full/287/ 2/G491you'll also see that the other omega-3 fatty acid found in fish

oil, eicosapentaenoic acid (EPA), is also pretty effective in reducing bile-duct injury, although the authors conclude that it is not statistically significant (see Fig. 4).The more recent research from Freedman's group suggests that the DHA is activating and/or inducing the nuclear receptor PPAR-alpha (and perhaps also RXR-alpha) to prevent bile-duct injury in these mice.Pall H, Zaman MM, Andersson C, Freedman SD 2006 Decreased peroxisome proliferator activated receptor alpha is associated with bile duct injury in cystic fibrosis transmembrane conductance regulator-/- mice. J. Pediatr. Gastroenterol. Nutr. 42: 275-281. http://www.ncbi. nlm.nih.gov/ pubmed/16540796Because children with PSC seem to have a defect in cystic fibrosis gene function:Pall H, Zielenski J, Jonas MM, Dasilva DA, Potvin KM,

Yuan, XW, Huang Q, Freedman SD 2007 Primary sclerosing cholangitis in childhood is associated with abnormalities in cystic fibrosis-mediated chloride channel function. J. Pediatr. 151: 255-259.http://www.ncbi. nlm.nih.gov/ pubmed/17719933this is the rationale for the ongoing trial of DHA in the treatment of PSC:http://www.clinical trials.gov/ ct2/show/ NCT00325013We'll have more to say about the preliminary results from this trial in a few days.If you look up CFTR in the Online Mendelian Inheritance in Man database, it has this to say about CFTR and PSC:"Primary sclerosing cholangitis (PSC), a slowly progressive cholestatic liver disease characterized by fibroobliterative inflammation of the biliary

tract, leads to cirrhosis and portal hypertension and is a major indication for liver transplantation. Sheth et al. (2003) stated that 75 to 80% of cases were associated with inflammatory bowel disease (IBD; 266600) and that 2.5 to 7.5% of patients with IBD develop PSC (Lee and Kaplan, 1995). Sheth et al. (2003) hypothesized that dysfunction of CFTR may explain why a subset of patients with IBD develop PSC. They prospectively evaluated CFTR genotype and phenotype in 19 patients with PSC compared with 18 patients with IBD and no liver disease, 17 with primary biliary cirrhosis (PBC; 109720), 81 with CF, and 51 healthy controls. They found an increased prevalence of CFTR abnormalities in heterozygous state in PSC as demonstrated by molecular and functional analyses, and concluded that these abnormalities may contribute to the development of PSC in a subset of patients with IBD. Eighty-nine percent of

PSC patients carried genotypes containing the 1540G variant (602421.0023) resulting in decreased functional CFTR compared with 57% of disease controls (P = 0.03). Only 1 of 19 PSC patients had neither a CFTR mutation nor the 1540G variant. CFTR chloride channel function assessed by nasal potential difference testing demonstrated a reduced median isoproterenol response in PSC patients compared with disease controls and healthy controls." http://www.ncbi. nlm.nih.gov/ entrez/dispomim. cgi?id=602421It's not clear whether the bile-duct injury in the mouse model can be reversed once it has taken place. If the colitis is causing a damage to the intestinal barrier that then allows bacterial toxins and/or bacteria to enter the blood stream and reach the liver, then it might be expected that stopping the

intestinal inflammation might delay progression of the liver disease? But others suggest that the course of PSC is independent of intestinal inflammation.I hope this answers all of your questions.Best regards,Dave (father of (23); PSC 07/03; UC 08/03)>> Dave, how interesting. > > How do they give a mouse Colitis? What do they the mouse? It sounds like colitis causes PSC. It seems like many people who have PSC have colitis. My dad who has psc does not have colitis or perhaps he does without the symtoms. PSC is not reverseable right? Would treating Colitis stop further progression

of PSC? Sorry about all of these questions.> > Lori A.

[Guest guest]

Hi Dave, Thanks for all that good info.

Would you be willing to share how much fish oil your son takes per day and what kind? Also, what vitamins is he taking per day.? My dad does take fish oil.

I told my Dad about our emails and he wanted me to ask you if you have ever heard about "Icelandic Fish Oil". I guess it is formula that includes other things but the main ingredient is fish oil. I think this is the product link but not sure. http://www.icelandhealth.com/hw020315.html

http://www.icelandhealth.com/maxo3l.html I have pretty bad Psoriasis and I am thinking I might start taking fish oil as well. Perhaps it will help to relieve my symptoms. I was told Psoriasis is an autoimmune disease but I don't know. I know the symptoms I have are only a reflection of what is going on inside. Thanks a lot,

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

Re: Interesting article: cystic fibrosis pig model

Hi Lori;Yes, the DHA (and to a lesser extent EPA) largely prevents the bile-duct injury when the cftr (-/-) mice are given colitis.My son has been taking fish oils for the past 3 years and we are hoping that this may delay PSC disease progression ... assuming that similar mechanisms may be involved? Certainly his liver function tests are now the best they have been since diagnosis (5 years ago), and this is all that we have to go on at present.I believe that others in the support group have been taking either DHA alone, or fish oils (combination of EPA and DHA) and have reported improvements in their liver function tests (e.g. reduced serum alkaline phosphatase) . Perhaps others will chime in on this topic?I am not in the medical field ... actually I'm a plant biochemist. But I have read a lot about PSC, IBD, and autoimmune diseases in the past 5 years, and most everything

I've read about fish oils is that they are good for human health in general. You can find a collection of over 2,000 papers on fish oils here:http://www.psc- literature. org/fishoil. htmIf I were to pick out some good (and free) review articles, it would be these:Calder PC, Grimble RF 2002 Polyunsaturated fatty acids, inflammation and immunity. Eur. J. Clin. Nutr. 56 Suppl. 3: S14-S19.http://www.ncbi. nlm.nih.gov/ pubmed/12142955Calder PC 2006 n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am. J. Clin. Nutr. 83: 1505S-1519S.http://www.ncbi. nlm.nih.gov/ pubmed/16841861Simopoulos AP 2002 Omega-3 fatty acids in

inflammation and autoimmune diseases. J. Am. Coll. Nutr. 21: 495-505. http://www.ncbi. nlm.nih.gov/ pubmed/12480795Because I am not a doctor of medicine, I can't say that all PSCers should take fish oils. But I can present some sound information here, and perhaps this may encourage some members to talk with their hepatologists about this option.Best regards,Dave R.>> If I am understanding right, The fish oil or omega 3 or DHA (all the same thing) fixes the bile duct injury? Or prevents it from getting worse after the injury? Looks like PSCers should be taking fish

oil!> Dave, are you in the medical field. Just curious.> > Lori A. >