Re: Severe PSC itching/Carolyn

[Guest guest]

Carolyn, what is that antibiotic that you started on? Jan's post

reminds me of your experience with being able to eat a variety of

foods again. Jan, hang in there.

Martha (MA)

Have tried every med. for this condition & some

> worked in the beginning but no longer are effective and my life is a

> living nightmare. Also, I'm not able to eat any

> food or drink other than chick., pot., plain lettuce & onion as it

> seems to bring on more attacks or aggravate PSC esp. in the lower

> leg, ft., etc area. So I'm down to 85 lbs (hgt 5'4 " ) (was prev.

> able to eat all foods up until 2005). My question is this. The

> doctor has never heard of anyone w/this disease that has had prob

> w/food aggravating the pruitis from psc. ...Jan

>

[Guest guest]

Martha wrote:

>

> Carolyn, what is that antibiotic that you started on? Jan's post

> reminds me of your experience with being able to eat a variety of

> foods again. Jan, hang in there.

Hi Martha!

The miracle med is Xifaxan (rifaximin) -- an antibiotic which works

exclusively in the gut. It's given for hepatic encephalopathy (and it

has worked magnificently for that in my case!), but they are also

finding that it will put about 52% of Crohn's cases into a deep, deep

remission.

Yes, I'm eating (and loving!) fruits & veggies again for the first time

in 26 years without all the pain, diarrhea, etc., etc. However, I did

learn today that I still can't handle cinnamon. :-(

(Last night I had 2 pieces of cinnamon toast and today have been running

to the bathroom, trying not to trip over the cats as I go!).

Regards,

Carolyn B. in SC

[Guest guest]

Hi Carolyn;

Until recently, I thought that since xifaxan (rifaximin) was a " non-

absorbable " antibiotic it would not activate the pregnane X receptor,

like its absorbable, parent compound rifampin (rifampicin). I was

wrong about this. Rifaximin does seem to activate the pregnane X

receptor (PXR) in the gut, but not in the liver:

_________________

J Pharmacol Exp Ther. 2007 Apr 18; [Epub ahead of print]

Rifaximin is a gut-specific human pregnane X receptor activator.

Ma X, Shah YM, Guo GL, Wang T, Krausz KW, Idle JR, FJ.

National Cancer Institute.

Rifaximin, a rifamycin analogue approved for the treatment of

travelers' diarrhea, is also beneficial in the treatment of multiple

chronic gastrointestinal disorders. However, the mechanisms

contributing to the effects of rifaximin on chronic gastrointestinal

disorders are not fully understood. In the current study, rifaximin

was investigated for its role in activation of the pregnane X

receptor (PXR), a nuclear receptor that regulates a genes involved in

xenobiotic and limited endobiotic deposition and detoxication. PXR-

humanized (hPXR), Pxr-null, and wild-type mice were treated orally

with rifaximin, and rifampicin, a well-characterized human PXR

ligand. Rifaximin was highly concentrated in the intestinal tract

when compared to rifampicin. Rifaximin treatment resulted in

significant induction of PXR target genes in the intestine of hPXR

mice, but not in wild-type and Pxr-null mice. However, rifaximin

treatment demonstrated no significant effect on hepatic PXR target

genes in wild-type, Pxr-null, and hPXR mice. Consistent with the in

vivo data, cell-based reporter gene assay revealed rifaximin-mediated

activation of human PXR, but not the other xenobiotic nuclear

receptors CAR, PPARalpha, PPARgamma, and FXR. Pretreatment with

rifaximin did not affect the pharmacokinetics of the CYP3A substrate

midazolam, but increased the Cmax and decreased Tmax of 1'-

hydroxymidazolam. Collectively, the current study identified

rifaximin as a gut-specific human PXR ligand, and provided further

evidence for the utility of hPXR mice as a critical tool for the

study of human PXR activators. Further human studies are suggested to

assess the potential role of rifaximin-mediated gut PXR activation in

therapeutics of chronic gastrointestinal disorders. PMID: 17442842.

http://jpet.aspetjournals.org/cgi/reprint/jpet.107.121913v1

_________________

Rifampin, however, activates PXR both in the gut and liver.

In our last newsletter we talked about the role of inflammation in

down-regulating PXR, potentially contributing to impaired

detoxification of bile acids and xenobiotics, and contributing to

cholestasis. Conversely, activation of PXR by rifampin, might

counteract these processes, and have anti-inflammatory effects:

http://www.pscpartners.org/NewsVol-2-4.pdf

One wonders if activation of PXR in the gut by rifaximin could be

counteracting the gut inflammation in Crohn's disease, helping to

bring it into remission?

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

> The miracle med is Xifaxan (rifaximin) -- an antibiotic which works

exclusively in the gut. It's given for hepatic encephalopathy (and

it has worked magnificently for that in my case!), but they are also

finding that it will put about 52% of Crohn's cases into a deep,

deep remission.

[Guest guest]

Dear ,

Say what???????? LOL! I'm terribly sorry but my HE-clouded mind

doesn't have a clue as to what you just wrote me!!! Could you please

interpret for me? (The xifaxan helps the HE tremendously, but not

enough for me to absorb and understand anything complex anymore.)

The only additional clue I can give re: Xifaxan, is that my dr. said the

current theory is that Crohn's may start as an overblown out-of-control

reaction to a simple infection in the gut, and that's why they think the

Xifaxan puts it into such deep remission. Do away with the bacterial

source of the infection and you won't have to deal with the overblown

reaction to it.

Does that go along with what you sent me? Many thanks for all your help!!

Regards,

Carolyn B. in SC

============================================

wrote:

>

> Hi Carolyn;

>

> Until recently, I thought that since xifaxan (rifaximin) was a " non-

> absorbable " antibiotic it would not activate the pregnane X receptor,

> like its absorbable, parent compound rifampin (rifampicin). I was

> wrong about this. Rifaximin does seem to activate the pregnane X

> receptor (PXR) in the gut, but not in the liver:

>

> _________________

>

> J Pharmacol Exp Ther. 2007 Apr 18; [Epub ahead of print]

>

> Rifaximin is a gut-specific human pregnane X receptor activator.

>

> Ma X, Shah YM, Guo GL, Wang T, Krausz KW, Idle JR, FJ.

>

> National Cancer Institute.

>

> Rifaximin, a rifamycin analogue approved for the treatment of

> travelers' diarrhea, is also beneficial in the treatment of multiple

> chronic gastrointestinal disorders. However, the mechanisms

> contributing to the effects of rifaximin on chronic gastrointestinal

> disorders are not fully understood. In the current study, rifaximin

> was investigated for its role in activation of the pregnane X

> receptor (PXR), a nuclear receptor that regulates a genes involved in

> xenobiotic and limited endobiotic deposition and detoxication. PXR-

> humanized (hPXR), Pxr-null, and wild-type mice were treated orally

> with rifaximin, and rifampicin, a well-characterized human PXR

> ligand. Rifaximin was highly concentrated in the intestinal tract

> when compared to rifampicin. Rifaximin treatment resulted in

> significant induction of PXR target genes in the intestine of hPXR

> mice, but not in wild-type and Pxr-null mice. However, rifaximin

> treatment demonstrated no significant effect on hepatic PXR target

> genes in wild-type, Pxr-null, and hPXR mice. Consistent with the in

> vivo data, cell-based reporter gene assay revealed rifaximin-mediated

> activation of human PXR, but not the other xenobiotic nuclear

> receptors CAR, PPARalpha, PPARgamma, and FXR. Pretreatment with

> rifaximin did not affect the pharmacokinetics of the CYP3A substrate

> midazolam, but increased the Cmax and decreased Tmax of 1'-

> hydroxymidazolam. Collectively, the current study identified

> rifaximin as a gut-specific human PXR ligand, and provided further

> evidence for the utility of hPXR mice as a critical tool for the

> study of human PXR activators. Further human studies are suggested to

> assess the potential role of rifaximin-mediated gut PXR activation in

> therapeutics of chronic gastrointestinal disorders. PMID: 17442842.

>

> http://jpet.aspetjournals.org/cgi/reprint/jpet.107.121913v1

> <http://jpet.aspetjournals.org/cgi/reprint/jpet.107.121913v1>

>

> _________________

>

> Rifampin, however, activates PXR both in the gut and liver.

>

> In our last newsletter we talked about the role of inflammation in

> down-regulating PXR, potentially contributing to impaired

> detoxification of bile acids and xenobiotics, and contributing to

> cholestasis. Conversely, activation of PXR by rifampin, might

> counteract these processes, and have anti-inflammatory effects:

>

> http://www.pscpartners.org/NewsVol-2-4.pdf

> <http://www.pscpartners.org/NewsVol-2-4.pdf>

>

> One wonders if activation of PXR in the gut by rifaximin could be

> counteracting the gut inflammation in Crohn's disease, helping to

> bring it into remission?

>

> Best regards,

>

> Dave

> (father of (21); PSC 07/03; UC 08/03)

[Guest guest]

Sorry Carolyn;

I'm just thinking that in addition to acting as an antibiotic (killing

bacteria) it might be giving an added bonus of inhibiting inflammation,

helping to bring the Crohn's disease into remission?

Best regards,

Dave R.

> Say what????????

[Guest guest]

> Have tried every med. for this condition & some

> > worked in the beginning but no longer are effective and my life

is a

> > living nightmare. Also, I'm not able to eat any

> > food or drink other than chick., pot., plain lettuce & onion as

it

> > seems to bring on more attacks or aggravate PSC esp. in the

lower

> > leg, ft., etc area. So I'm down to 85 lbs (hgt 5'4 " ) (was prev.

> > able to eat all foods up until 2005). My question is this. The

> > doctor has never heard of anyone w/this disease that has had

prob

> > w/food aggravating the pruitis from psc. ...Jan

> >

>