Glycine-conjugated bile acids and PSC

December 12, 2008

I thought that this paper was interesting ....

NMR Biomed. 2008 Dec 9. [Epub ahead of print]

Absence of glycochenodeoxycholic acid (GCDCA) in human bile is an

indication of cholestasis: a (1)H MRS study.

Ijare OB, Bezabeh T, Albiin N, Arnelo U, Bergquist A, Lindberg B,

IC

NRC Institute for Biodiagnostics, Winnipeg, Canada.

The utility of (1)H MR spectroscopy in detecting chronic cholestasis

has been investigated. The amide proton region of the (1)H MR

spectrum of human bile plays a major role in differentiating

cholestatic (Ch) patterns from the normal ones. Bile obtained from

normal bile ducts contains both taurine and glycine conjugates of

bile acids - cholic acid (CA), chenodeoxycholic acid (CDCA), and

deoxycholic acid (DCA). Absence of a glycine-conjugated bile acid

glycochenodeoxycholic acid (GCDCA) has been observed in bile samples

obtained from primary sclerosing cholangitis (PSC) patients. A total

of 32 patients with various hepatobiliary diseases were included in

the study. Twenty-one patients had PSC and 11 had normal

cholangiograms. One PSC patient was excluded from the study because

of a bad spectrum. Seventeen out of the 20 PSC patients showed an

absence of GCDCA in their (1)H MR spectrum of bile. Six of the 11

reference patients with normal cholangiogram also showed spectra

similar to those of PSC, indicating the possibility of cholestasis.

DQF-COSY and TOCSY experiments performed on bile samples from PSC

patients also revealed absence of phosphatidylcholine (PC) in some of

the bile samples, suggesting possible damage to the cholangiocytes by

the toxic bile. These observations suggest that analysis of human

bile by (1)H MRS could be of value in the diagnosis of chronic Ch

liver disorders. PMID: 19067402.

Best regards,

Dave

(father of (23), PSC 07/03; UC 08/03)

December 13, 2008

Is this GCDCA bile the one Urso is meant to replace or stimulate?

ee

>

> I thought that this paper was interesting ....

>

December 13, 2008

Is this GCDCA bile the one Urso is meant to replace or stimulate?

ee

>

> I thought that this paper was interesting ....

>

December 13, 2008

Hi ee,

Yes,I think the urso would be replacing this. When urso is supplied

to PSC patients, the urso (UDCA) gets rapidly converted mostly to its

glycine-conjugate, as described in this paper:

Hepatology. 2004 Sep;40(3):693-8.

Effect of high-dose ursodeoxycholic acid on its biliary enrichment in

primary sclerosing cholangitis.

Rost D, Rudolph G, Kloeters-Plachky P, Stiehl A

Department of Medicine, University of Heidelberg, Heidelberg, Germany.

Ursodeoxycholic acid (UDCA) has beneficial effects in cholestatic

liver diseases. In primary sclerosing cholangitis (PSC), there is

evidence that high doses (+/- 20 mg/kg) of UDCA may be more effective

than average doses. Biliary enrichment of UDCA at such high doses may

represent the decisive factor for its beneficial effect. Up to now it

is not clear how high-dose UDCA correlates with its biliary

enrichment and whether bacterial degradation of large amounts of UDCA

may lead to an increased bacterial formation of more toxic

hydrophobic bile acids. We determined the biliary bile acid

composition in 56 patients with PSC including 30 patients with repeat

bile samples treated with various doses of UDCA. At a UDCA dose of 10-

13 mg/kg/d (n = 18) biliary UDCA represented 43.1% + 0.3% (mean + SD)

of total bile acids; at a UDCA dose of 14-17 mg/kg (n = 14), its

biliary content increased to 46.9% + 0.3%, at 18-21 mg/kg (n = 34) to

55.9% + 0.2%, at 22-25 mg/kg (n = 12) to 58.6% + 2.3%, and at 26-32

mg/kg (n = 8) to 57.7% + 0.4%. During UDCA treatment, the biliary

content of all other bile acids was unchanged or decreased. In

conclusion, biliary enrichment of UDCA increases with increasing dose

and reaches a plateau at 22-25 mg/kg. There was no increase of toxic

hydrophobic bile acids. If biliary enrichment of UDCA represents the

decisive factor for its clinical effect, it seems likely that UDCA

doses of up to 22-25 mg/kg may be more effective than lower doses.

PMID: 15349909

Full text article available at:

http://www3.interscience.wiley.com/cgi-bin/fulltext/109606288/PDFSTART

" When administered orally, unconjugated UDCA on the first pass

through the liver is rapidly conjugated with glycine or taurine.46

After UDCA, bile was mainly enriched with the glycine conjugate of

UDCA, and at very high UDCA doses this percentage increased only a

little (Table 3). "

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

> Is this GCDCA bile the one Urso is meant to replace

December 13, 2008