RE: Medical Treatment of Primary Sclerosing Cholangitis

[Guest guest]

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....had high blood pressure untreated and smoked all his life,,,,my son's paternal grandfather fell out in the backk yard at 44 ...had a quad bypass and is now 83,,,,my son's paternal great grandfather died early 40's heart attack.

This seems to be my genetic link ?

Also are you familiar with the Foundation started in 2004 for research for PSC ......Worth is about your son's age.....he is -Keegan's son or grandson......well I went to see his doctor about infliximab but he said only as a last resort...just curious

MARNA

Subject: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 11:44 AM

Clin Rev Allergy Immunol. 2008 Aug 28. [Epub ahead of print]Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptio nal Modulators?Beuers U, Kullak-Ublick GA, Pusl T, Rauws ER, Rust CDepartment of Gastroenterology and Hepatology, G4-213, Academic Medical Center, University of Amsterdam, P. O. Box 22700, 1100, DE, Amsterdam, The Netherlands, u.h.beuers (AT) amc (DOT) uv.nl.Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult.

Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator- activator receptors (PPARs)

have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC. PMID: 18751930 ____________ _________ ____Dave (father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....had high blood pressure untreated and smoked all his life,,,,my son's paternal grandfather fell out in the backk yard at 44 ...had a quad bypass and is now 83,,,,my son's paternal great grandfather died early 40's heart attack.

This seems to be my genetic link ?

Also are you familiar with the Foundation started in 2004 for research for PSC ......Worth is about your son's age.....he is -Keegan's son or grandson......well I went to see his doctor about infliximab but he said only as a last resort...just curious

MARNA

Subject: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 11:44 AM

Clin Rev Allergy Immunol. 2008 Aug 28. [Epub ahead of print]Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptio nal Modulators?Beuers U, Kullak-Ublick GA, Pusl T, Rauws ER, Rust CDepartment of Gastroenterology and Hepatology, G4-213, Academic Medical Center, University of Amsterdam, P. O. Box 22700, 1100, DE, Amsterdam, The Netherlands, u.h.beuers (AT) amc (DOT) uv.nl.Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult.

Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator- activator receptors (PPARs)

have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC. PMID: 18751930 ____________ _________ ____Dave (father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....had high blood pressure untreated and smoked all his life,,,,my son's paternal grandfather fell out in the backk yard at 44 ...had a quad bypass and is now 83,,,,my son's paternal great grandfather died early 40's heart attack.

This seems to be my genetic link ?

Also are you familiar with the Foundation started in 2004 for research for PSC ......Worth is about your son's age.....he is -Keegan's son or grandson......well I went to see his doctor about infliximab but he said only as a last resort...just curious

MARNA

Subject: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 11:44 AM

Clin Rev Allergy Immunol. 2008 Aug 28. [Epub ahead of print]Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptio nal Modulators?Beuers U, Kullak-Ublick GA, Pusl T, Rauws ER, Rust CDepartment of Gastroenterology and Hepatology, G4-213, Academic Medical Center, University of Amsterdam, P. O. Box 22700, 1100, DE, Amsterdam, The Netherlands, u.h.beuers (AT) amc (DOT) uv.nl.Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult.

Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator- activator receptors (PPARs)

have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC. PMID: 18751930 ____________ _________ ____Dave (father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Marna -

I didn't see your original posting, but the family history of heart disease alone would make it valuable to have children and grandchildren evaluated at an early age for hyperlipidemia (high cholesterol) and checked for high blood pressure. Some teens are started on statins to reduce cholesterol when there is family history of heart disease and/or sudden death at an early age. And of course the "usual" healthy measures to reduce risk - regular exercise, healthy diet, no smoking, etc!

Joanne H

(, Ca., mom of , 18, UC/PSC 2-06; Rheum Arthritis 98)

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....my son's paternal great grandfather died early 40's heart attack.

MARNA

[Guest guest]

Marna -

I didn't see your original posting, but the family history of heart disease alone would make it valuable to have children and grandchildren evaluated at an early age for hyperlipidemia (high cholesterol) and checked for high blood pressure. Some teens are started on statins to reduce cholesterol when there is family history of heart disease and/or sudden death at an early age. And of course the "usual" healthy measures to reduce risk - regular exercise, healthy diet, no smoking, etc!

Joanne H

(, Ca., mom of , 18, UC/PSC 2-06; Rheum Arthritis 98)

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....my son's paternal great grandfather died early 40's heart attack.

MARNA

[Guest guest]

Marna -

I didn't see your original posting, but the family history of heart disease alone would make it valuable to have children and grandchildren evaluated at an early age for hyperlipidemia (high cholesterol) and checked for high blood pressure. Some teens are started on statins to reduce cholesterol when there is family history of heart disease and/or sudden death at an early age. And of course the "usual" healthy measures to reduce risk - regular exercise, healthy diet, no smoking, etc!

Joanne H

(, Ca., mom of , 18, UC/PSC 2-06; Rheum Arthritis 98)

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....my son's paternal great grandfather died early 40's heart attack.

MARNA

[Guest guest]

Thank you I am definately going to keep up on it now.

Though he just has PSC ,,,and non of the other males did. I did get the doctors to draw cardiac enzymes or something once because I was noticing that he had body wide inflammation and they had not checked his heart. Seems from day one I have had to tell them what to do and then give them the money ! ....sigh....

There basic premise has been bring him back when he turns yellow !

Marna

Subject: RE: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 4:37 PM

Marna -

I didn't see your original posting, but the family history of heart disease alone would make it valuable to have children and grandchildren evaluated at an early age for hyperlipidemia (high cholesterol) and checked for high blood pressure. Some teens are started on statins to reduce cholesterol when there is family history of heart disease and/or sudden death at an early age. And of course the "usual" healthy measures to reduce risk - regular exercise, healthy diet, no smoking, etc!

Joanne H

(, Ca., mom of , 18, UC/PSC 2-06; Rheum Arthritis 98)

Thank you

I just recently or maybe I saw it earlier and forgot about it but the link between arteriosclerosis and PSC.

The reason this interest me so is that my son's father died at 41 of heart attack....my son's paternal great grandfather died early 40's heart attack.

MARNA

[Guest guest]

Hi Marna;

Trauner's group has proposed the link between atherosclerosis

and PSC:

Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -

the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.

http://www.ncbi.nlm.nih.gov/pubmed/17254334

I have heard about the 's and their foundation. I met ,

Musette and their son, Worth, in 2006 when I attended a

Foundation scientific advisory board meeting in Memphis, and had

dinner with them at their house (or should I say, mansion!). Musette

attended the PSC Partners Seeking a Cure conference in

ville this spring. I am very grateful to them for funding PSC

research at such a significant level.

Best regards,

Dave R.

[Guest guest]

Hi Marna;

Trauner's group has proposed the link between atherosclerosis

and PSC:

Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -

the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.

http://www.ncbi.nlm.nih.gov/pubmed/17254334

I have heard about the 's and their foundation. I met ,

Musette and their son, Worth, in 2006 when I attended a

Foundation scientific advisory board meeting in Memphis, and had

dinner with them at their house (or should I say, mansion!). Musette

attended the PSC Partners Seeking a Cure conference in

ville this spring. I am very grateful to them for funding PSC

research at such a significant level.

Best regards,

Dave R.

[Guest guest]

Hi Marna;

Trauner's group has proposed the link between atherosclerosis

and PSC:

Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -

the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.

http://www.ncbi.nlm.nih.gov/pubmed/17254334

I have heard about the 's and their foundation. I met ,

Musette and their son, Worth, in 2006 when I attended a

Foundation scientific advisory board meeting in Memphis, and had

dinner with them at their house (or should I say, mansion!). Musette

attended the PSC Partners Seeking a Cure conference in

ville this spring. I am very grateful to them for funding PSC

research at such a significant level.

Best regards,

Dave R.

[Guest guest]

Hi ,

Dr. Whitington talked with me about Worth and he did not want to risk putting my son in the research.....even though he said he saw thousands and none of them looked as healthy as my son.

Maybe because my son had such an early diagnosis at age 3,,,,World Wide Prayer, Very Good Probiotics, conservative doctors that have kept him off steroids and he has seen the best in Texas, Louisiana, Dr. Whitington ( Worth 's doctor ), and I have called coast to coast, in addition top Dr. Moreno PHD only naturopath allowed to practice in hospitals in 2004 in Louisiana,,,,whom was referred by Dr. Jordan Rubin.

He said Worth was really sick and he was able to get him into a semi remission with infliximab which they are using frequently with Crohns. He said only as a last resort though.

I found them because my 24 year old brother was tragically killed in a work truck accident in 2004. After his death I am on the internet and for the first time since my son had been sick I see a researchh group dedicated to children and seeking a cure for PSC.

I felt it a gift from heaven as my brother's name was MORGAN I believe it was founded shortly after his death.....it certainly made me cry and get on a plane to Memphis !

Sincerely thank you for information in the puzzles we are trying to solve.

Marna and Wesley and Colin

Subject: Re: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 8:15 PM

Hi Marna; Trauner's group has proposed the link between atherosclerosis and PSC:Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.http://www.ncbi. nlm.nih.gov/ pubmed/17254334I have heard about the 's and their foundation. I met , Musette and their son, Worth, in 2006 when I attended a Foundation scientific advisory board meeting in Memphis, and had dinner with them at their house (or should I say, mansion!). Musette attended the PSC Partners Seeking a Cure conference in ville this spring. I am very grateful to them for funding PSC research at such a significant level.Best regards,Dave R.

[Guest guest]

Hi ,

Dr. Whitington talked with me about Worth and he did not want to risk putting my son in the research.....even though he said he saw thousands and none of them looked as healthy as my son.

Maybe because my son had such an early diagnosis at age 3,,,,World Wide Prayer, Very Good Probiotics, conservative doctors that have kept him off steroids and he has seen the best in Texas, Louisiana, Dr. Whitington ( Worth 's doctor ), and I have called coast to coast, in addition top Dr. Moreno PHD only naturopath allowed to practice in hospitals in 2004 in Louisiana,,,,whom was referred by Dr. Jordan Rubin.

He said Worth was really sick and he was able to get him into a semi remission with infliximab which they are using frequently with Crohns. He said only as a last resort though.

I found them because my 24 year old brother was tragically killed in a work truck accident in 2004. After his death I am on the internet and for the first time since my son had been sick I see a researchh group dedicated to children and seeking a cure for PSC.

I felt it a gift from heaven as my brother's name was MORGAN I believe it was founded shortly after his death.....it certainly made me cry and get on a plane to Memphis !

Sincerely thank you for information in the puzzles we are trying to solve.

Marna and Wesley and Colin

Subject: Re: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 8:15 PM

Hi Marna; Trauner's group has proposed the link between atherosclerosis and PSC:Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.http://www.ncbi. nlm.nih.gov/ pubmed/17254334I have heard about the 's and their foundation. I met , Musette and their son, Worth, in 2006 when I attended a Foundation scientific advisory board meeting in Memphis, and had dinner with them at their house (or should I say, mansion!). Musette attended the PSC Partners Seeking a Cure conference in ville this spring. I am very grateful to them for funding PSC research at such a significant level.Best regards,Dave R.

[Guest guest]

Hi ,

Dr. Whitington talked with me about Worth and he did not want to risk putting my son in the research.....even though he said he saw thousands and none of them looked as healthy as my son.

Maybe because my son had such an early diagnosis at age 3,,,,World Wide Prayer, Very Good Probiotics, conservative doctors that have kept him off steroids and he has seen the best in Texas, Louisiana, Dr. Whitington ( Worth 's doctor ), and I have called coast to coast, in addition top Dr. Moreno PHD only naturopath allowed to practice in hospitals in 2004 in Louisiana,,,,whom was referred by Dr. Jordan Rubin.

He said Worth was really sick and he was able to get him into a semi remission with infliximab which they are using frequently with Crohns. He said only as a last resort though.

I found them because my 24 year old brother was tragically killed in a work truck accident in 2004. After his death I am on the internet and for the first time since my son had been sick I see a researchh group dedicated to children and seeking a cure for PSC.

I felt it a gift from heaven as my brother's name was MORGAN I believe it was founded shortly after his death.....it certainly made me cry and get on a plane to Memphis !

Sincerely thank you for information in the puzzles we are trying to solve.

Marna and Wesley and Colin

Subject: Re: Medical Treatment of Primary Sclerosing CholangitisTo: Date: Sunday, August 31, 2008, 8:15 PM

Hi Marna; Trauner's group has proposed the link between atherosclerosis and PSC:Fickert P, Moustafa T, Trauner M 2007 Primary sclerosing cholangitis -the arteriosclerosis of the bile duct? Lipids Health Dis. 6: 3.http://www.ncbi. nlm.nih.gov/ pubmed/17254334I have heard about the 's and their foundation. I met , Musette and their son, Worth, in 2006 when I attended a Foundation scientific advisory board meeting in Memphis, and had dinner with them at their house (or should I say, mansion!). Musette attended the PSC Partners Seeking a Cure conference in ville this spring. I am very grateful to them for funding PSC research at such a significant level.Best regards,Dave R.