Hydroxychloroquine Use May Be Safe in Systemic Lupus Erythematosus
"Because of its broad spectrum of benefits and safety profile, hydroxychloroquine should be given to most patients with systemic lupus erythematosus (SLE) during the whole course of the disease, regardless of severity, and should be continued during pregnancy, according to the results of a systematic review reported in the June 3 Online First issue of Annals of the Rheumatic Diseases."
---------
"Hydroxychloroquine"
The iron-binding and hydroxyl radical scavenging action of anti- inflammatory drugs. Xenobiotica. 1988 Apr;18(4):459-70. Aruoma OI, Halliwell B.
Department of Biochemistry, University of London King's College, Strand Campus, UK.
1. Hydroxyl radicals (.OH) are thought to be generated at sites of inflammation and to contribute to tissue damage. All anti-inflammatory drugs tested were able to scavenge .OH generated in free solution at almost diffusion- controlled rates (rate constants about 10(10)M-1s-1). 2. Much .OH generation in vivo occurs at specific sites, where bound metal ions (such as Fe2+) react with H2O2 to produce .OH that immediately attacks the site. Only .OH scavengers that have sufficient metal-binding ability to withdraw metal ions from this site can protect against site-specific damage. 3. All anti-inflammatory drugs tested were able to protect against site-specific damage by .OH in a simple model system in vitro. Penicillamine, diclofenac sodium, piroxicam, azathioprine, primaquine, chloroquine and hydroxychloroquine were especially effective. 4. The ability of an anti-inflammatory drug to protect against .OH formation in vivo depends not only on its rate constant for reaction with .OH, but also on its metal-binding ability and on the geometry and redox potential of any metal complex formed.
PMID: 3135672
----------------------
Anyone care to venture a guess why phlebotomy / bloodletting hasn't even been tried in lupus when a drug that is supposed to BE .. an **alternative** TO **bloodletting** .. IS .. now .. readily prescribed .. ?
"Hydroxychloroquine should be the preferred alternative to phlebotomy"
Plaquenil - Plaquenil Side Effects - Plaquenil Hydroxychloroquine has been beneficial for a high percentage of patients with rheumatoid arthritis and lupus erythematosus, especially chronic discoid lupus ...
"Hydroxychloroquine should be the preferred alternative to phlebotomy"
Photodermatol. 1984 Dec;1(6):286-92. Links A comparative trial of desferrioxamine and hydroxychloroquine for treatment of porphyria cutanea tarda in alcoholic patients.Marchesi L, Di Padova C, Cainelli T, Reseghetti A, Di Padova F, Rovagnati P, Cantoni L. Forty male alcoholic patients with porphyria cutanea tarda (PCT) were randomly assigned to 2 groups of 20. The 1st group received desferrioxamine (30 mg/kg body weight/day for 1 week every 3 months) whereas the latter was given hydroxychloroquine (200 mg twice/wk orally). Alcohol abstinence was advised for all patients. Improvement of cutaneous signs was evident after 6 months in hydroxychloroquine- treated subjects and after 12 months in desferrioxamine-treated subjects. At the end of the 1-year clinical trial, significant decreases of serum iron and ferritin were found in all patients, irrespective of the therapy. Urinary total porphyrins were reduced significantly in both groups, but the drop was significantly more evident in hydroxychloroquine- than in desferrioxamine-treated subjects. After 1 year of therapy, 4 desferrioxamine-treated patients vs 16 hydroxychloroquine-treated subjects acquired a normal urinary porphyrin pattern. These results indicate that hydroxychloroquine is more effective than desferrioxamine in inducing clinical and biochemical remission of PCT. Accordingly, hydroxychloroquine should be the preferred alternative to phlebotomy, if the latter is contraindicated.
On Jun 22, 2:52 pm, ironjustice <teamtan...@hotmail.com> wrote : iron- binding <<
"Intake of meat was associated with an increased risk and that the patients preferred fatty meat such as beef or pork" "These results suggest that dietary and reproductive factors may be responsible for the onset and the progression of SLE."
Female systemic lupus erythematosus in Miyagi Prefecture, Japan: a case-control study of dietary and reproductive factors. Tohoku J Exp Med. 1993 Mar;169(3):245-52. Minami Y, Sasaki T, Komatsu S, Nishikori M, Fukao A, Yoshinaga K, Hisamichi S. Department of Public Health, Tohoku University School of Medicine, Sendai.
To investigate risk factors of systemic lupus erythematosus (SLE) in relation to diet and reproduction, a population-based case-control study was conducted during the period from October 1988 to October 1989 in Miyagi Prefecture in northeastern Japan. Included in the study were 52 female patients with the recent SLE onset. Two sex- and birth year-matched (+/- 2 years) controls for each patient were selected from the general population. The analysis on diet showed that the frequent intake of meat was associated with an increased risk (frequent vs. rare, relative risk (RR) 3.36; 95% confidence interval (CI) 1.10-10.24) and that the patients preferred fatty meat such as beef or pork. The analysis on menstrual history revealed that menstrual irregularity was also associated with an increased risk (RR 3.79; 95% CI 1.43-10.01). These results suggest that dietary and reproductive factors may be responsible for the onset and the progression of SLE.
> Hydroxychloroquine Use May Be Safe in Systemic Lupus Erythematosus
> "Because of its broad spectrum of benefits and safety profile, > hydroxychloroquine should be given to most patients with systemic > lupus erythematosus (SLE) during the whole course of the disease, > regardless of severity, and should be continued during pregnancy, > according to the results of a systematic review reported in the June 3 > Online First issue of Annals of the Rheumatic Diseases."
> ---------
> "Hydroxychloroquine"
> The iron-binding and hydroxyl radical scavenging action of anti- > inflammatory drugs. > Xenobiotica. 1988 Apr;18(4):459-70. > Aruoma OI, Halliwell B.
> Department of Biochemistry, University of London King's College, > Strand Campus, UK.
> 1. Hydroxyl radicals (.OH) are thought to be generated at sites > of inflammation and to contribute to tissue damage. > All anti-inflammatory drugs tested were able to scavenge .OH > generated in free solution at almost diffusion- controlled rates > (rate constants about 10(10)M-1s-1). > 2. Much .OH generation in vivo occurs at specific sites, where > bound metal ions (such as Fe2+) react with H2O2 to produce > .OH that immediately attacks the site. > Only .OH scavengers that have sufficient metal-binding ability > to withdraw metal ions from this site can protect against > site-specific damage. > 3. All anti-inflammatory drugs tested were able to protect against > site-specific damage by .OH in a simple model system in vitro. > Penicillamine, diclofenac sodium, piroxicam, azathioprine, > primaquine, > chloroquine and hydroxychloroquine were especially effective. > 4. The ability of an anti-inflammatory drug to protect against .OH > formation in vivo depends not only on its rate constant for reaction > with .OH, but also on its metal-binding ability and on the geometry > and redox potential of any metal complex formed.
> PMID: 3135672
> ----------------------
> Anyone care to venture a guess why phlebotomy / bloodletting hasn't > even been tried in lupus when a drug that is supposed to BE .. an > **alternative** TO **bloodletting** .. IS .. now .. readily > prescribed .. ?
> "Hydroxychloroquine should be the preferred alternative to phlebotomy"
> Plaquenil - Plaquenil Side Effects - Plaquenil > Hydroxychloroquine has been beneficial for a high > percentage of patients with rheumatoid arthritis and lupus > erythematosus, especially chronic discoid lupus ...
> "Hydroxychloroquine should be the preferred alternative to phlebotomy"
> Photodermatol. 1984 Dec;1(6):286-92. Links > A comparative trial of desferrioxamine and hydroxychloroquine for > treatment of porphyria cutanea tarda in alcoholic patients.Marchesi > L, > Di Padova C, Cainelli T, Reseghetti A, Di Padova F, Rovagnati P, > Cantoni L. > Forty male alcoholic patients with porphyria cutanea tarda (PCT) were > randomly assigned to 2 groups of 20. The 1st group received > desferrioxamine (30 mg/kg body weight/day for 1 week every 3 months) > whereas the latter was given hydroxychloroquine (200 mg twice/wk > orally). Alcohol abstinence was advised for all patients. Improvement > of cutaneous signs was evident after 6 months in hydroxychloroquine- > treated subjects and after 12 months in desferrioxamine-treated > subjects. At the end of the 1-year clinical trial, significant > decreases of serum iron and ferritin were found in all patients, > irrespective of the therapy. Urinary total porphyrins were reduced > significantly in both groups, but the drop was significantly more > evident in hydroxychloroquine- than in desferrioxamine-treated > subjects. After 1 year of therapy, 4 desferrioxamine-treated patients > vs 16 hydroxychloroquine-treated subjects acquired a normal urinary > porphyrin pattern. These results indicate that hydroxychloroquine is > more effective than desferrioxamine in inducing clinical and > biochemical remission of PCT. Accordingly, hydroxychloroquine should > be the preferred alternative to phlebotomy, if the latter is > contraindicated.
On Jun 23, 1:26 pm, Ken <flakey...@earthlink.net> wrote: snip <<
You coprophagit atheists have been told my threads are NOT for you to congregate ..
ALL you repugnant fks were told to stay off my threads ..
Homosexual atheist shteaters .. were .. specifically .. TOLD ..
Write it .. down .. shteater ..
Giiiiit .. you .. mutated atheist shteater ..
Giiiiiit .. shteater ..
Git ..
-----------
"Intake of meat was associated with an increased risk and that the patients preferred fatty meat such as beef or pork" "These results suggest that dietary and reproductive factors may be responsible for the onset and the progression of SLE."
Female systemic lupus erythematosus in Miyagi Prefecture, Japan: a case-control study of dietary and reproductive factors. Tohoku J Exp Med. 1993 Mar;169(3):245-52. Minami Y, Sasaki T, Komatsu S, Nishikori M, Fukao A, Yoshinaga K, Hisamichi S. Department of Public Health, Tohoku University School of Medicine, Sendai.
To investigate risk factors of systemic lupus erythematosus (SLE) in relation to diet and reproduction, a population-based case-control study was conducted during the period from October 1988 to October 1989 in Miyagi Prefecture in northeastern Japan. Included in the study were 52 female patients with the recent SLE onset. Two sex- and birth year-matched (+/- 2 years) controls for each patient were selected from the general population. The analysis on diet showed that the frequent intake of meat was associated with an increased risk (frequent vs. rare, relative risk (RR) 3.36; 95% confidence interval (CI) 1.10-10.24) and that the patients preferred fatty meat such as beef or pork. The analysis on menstrual history revealed that menstrual irregularity was also associated with an increased risk (RR 3.79; 95% CI 1.43-10.01). These results suggest that dietary and reproductive factors may be responsible for the onset and the progression of SLE.
On Jun 23, 5:52 pm, ironjustice <teamtan...@hotmail.com> wrote: uroporphyrin <<
We have established .. CONCLUSIVELY .. **they** have DECIDED amongst themselves it would be "wise" to treat EACH AND EVERY ONE WITH LUPUS with a drug which is EXCLUSIVELY to be used INSTEAD of **bloodletting** .. but .. bloodletting has NEVER EVEN BEEN MENTIONED in the treatment of lupus patients .. EVER .. ever ..
Now either each and every lupus patient is .. stupid .. which is obviously I guess .. and each and every medical person is stupid .. ?
Or .. I .. am stupid ..
This shows vitamin C .. normally .. can offset a slight buildup of iron but WHEN the iron hits a 'certain level' the iron OVERWHELMS the vitamin C's **ability** to OFFSET this higher iron and the body cannot .. cope.
"Ascorbate suppresses hepatic URO accumulation at low, but not high hepatic iron levels"
This shows when the iron gets to a 'certain point' .. BOOM ..
"Was not observed until a high hepatic iron threshold was exceeded"
It shows it can be controlled by targeting the iron with diet and / or DIRECT iron targeting.
Uroporphyrin induces an autoimmune response / autoimmune like response.
Effect of iron and ascorbate on uroporphyria in ascorbate-requiring mice as a model for porphyria cutanea tarda. Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR Hepatology. 2006 Dec 22; 45(1): 187-194
Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies havesuggested a role for ascorbate (AA) in suppressing uroporphyria inAA-requiring rats (in the absence of excess iron), the present studyinvestigated whether AA could suppress uroporphyria produced byexcess hepatic iron. Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintainnear normal hepatic AA levels or a lower intake (75 ppm) that resulted in70% lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when irondextran (300-500 mg Fe/ kg) was administered. This effect of iron wasnot due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake. Conclusion: In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT.
(HEPATOLOGY2007;45:187-194.).
------------
Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda. Hepatology. 2007 Sep 13; Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR. Veterans Affairs Medical Center, White River Junction, VT.
Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used Hfe(-/-) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron- deficient diets. Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5- aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL/6 Hfe(-/-) mice treated with ALA and a CYP1A2 inducer. ALA- treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection. Conclusion: The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation. (HEPATOLOGY 2007.).
> "Intake of meat was associated with an increased risk and that the > patients preferred fatty meat such as beef or pork" > "These results suggest that dietary and reproductive factors may be > responsible for the onset and the progression of SLE."
> Female systemic lupus erythematosus in Miyagi Prefecture, Japan: a > case-control study of dietary and reproductive factors. > Tohoku J Exp Med. 1993 Mar;169(3):245-52. > Minami Y, Sasaki T, Komatsu S, > Nishikori M, Fukao A, Yoshinaga K, Hisamichi S. > Department of Public Health, Tohoku University School of Medicine, > Sendai.
> To investigate risk factors of systemic lupus erythematosus (SLE) in > relation to diet and reproduction, a population-based case-control > study was conducted during the period from October 1988 to October > 1989 in Miyagi Prefecture in northeastern Japan. > Included in the study were 52 female patients with the recent SLE > onset. > Two sex- and birth year-matched (+/- 2 years) controls for each > patient > were selected from the general population. > The analysis on diet showed that the frequent intake of meat was > associated with an increased risk (frequent vs. rare, relative risk > (RR) > 3.36; 95% confidence interval (CI) 1.10-10.24) and that the patients > preferred fatty meat such as beef or pork. > The analysis on menstrual history revealed that menstrual > irregularity > was also associated with an increased risk (RR 3.79; 95% CI > 1.43-10.01). > These results suggest that dietary and reproductive factors may be > responsible for the onset and the progression of SLE.
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On Jun 23, 5:52 pm, ironjustice <teamtan...@hotmail.com> wrote: uroporphyrin <<
We have established .. CONCLUSIVELY .. **they** have DECIDED amongst themselves it would be "wise" to treat EACH AND EVERY ONE WITH LUPUS with a drug which is EXCLUSIVELY to be used INSTEAD of **bloodletting** .. but .. bloodletting has NEVER EVEN BEEN MENTIONED in the treatment of lupus patients .. EVER .. ever ..
Now either each and every lupus patient is .. stupid .. which is obviously I guess .. and each and every medical person is stupid .. ?
Or .. I .. am stupid ..
This shows vitamin C .. normally .. can offset a slight buildup of iron but WHEN the iron hits a 'certain level' the iron OVERWHELMS the vitamin C's **ability** to OFFSET this higher iron and the body cannot .. cope.
"Ascorbate suppresses hepatic URO accumulation at low, but not high hepatic iron levels"
This shows when the iron gets to a 'certain point' .. BOOM ..
"Was not observed until a high hepatic iron threshold was exceeded"
It shows it can be controlled by targeting the iron with diet and / or DIRECT iron targeting.
Uroporphyrin induces an autoimmune response / autoimmune like response.
Effect of iron and ascorbate on uroporphyria in ascorbate-requiring mice as a model for porphyria cutanea tarda. Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR Hepatology. 2006 Dec 22; 45(1): 187-194
Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies havesuggested a role for ascorbate (AA) in suppressing uroporphyria inAA-requiring rats (in the absence of excess iron), the present studyinvestigated whether AA could suppress uroporphyria produced byexcess hepatic iron. Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintainnear normal hepatic AA levels or a lower intake (75 ppm) that resulted in70% lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when irondextran (300-500 mg Fe/ kg) was administered. This effect of iron wasnot due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake. Conclusion: In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT.
(HEPATOLOGY2007;45:187-194.).
------------
Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda. Hepatology. 2007 Sep 13; Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR. Veterans Affairs Medical Center, White River Junction, VT.
Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used Hfe(-/-) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron- deficient diets. Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5- aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL/6 Hfe(-/-) mice treated with ALA and a CYP1A2 inducer. ALA- treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection. Conclusion: The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation. (HEPATOLOGY 2007.).
This is as close to a .. gauntlet .. we are going to get ..
Somebody .. somewhere .. step up ..
There's gotta be a man amongst .. ya ..
We have established .. CONCLUSIVELY .. **they** have DECIDED amongst themselves it would be "wise" to treat EACH AND EVERY ONE WITH LUPUS with a drug which is EXCLUSIVELY to be used INSTEAD of **bloodletting** .. but .. bloodletting has NEVER EVEN BEEN MENTIONED in the treatment of lupus patients .. EVER .. ever ..
Now either each and every lupus patient is .. stupid .. which is obviously I guess .. and each and every medical person is stupid .. ?
Or .. I .. am stupid ..
This shows vitamin C .. normally .. can offset a slight buildup of iron but WHEN the iron hits a 'certain level' the iron OVERWHELMS the vitamin C's **ability** to OFFSET this higher iron and the body cannot .. cope.
"Ascorbate suppresses hepatic URO accumulation at low, but not high hepatic iron levels"
This shows when the iron gets to a 'certain point' .. BOOM ..
"Was not observed until a high hepatic iron threshold was exceeded"
It shows it can be controlled by targeting the iron with diet and / or DIRECT iron targeting.
Uroporphyrin induces an autoimmune response / autoimmune like response.
Effect of iron and ascorbate on uroporphyria in ascorbate-requiring mice as a model for porphyria cutanea tarda. Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR Hepatology. 2006 Dec 22; 45(1): 187-194
Excess hepatic iron is known to enhance both porphyria cutanea tarda (PCT) and experimental uroporphyria. Since previous studies havesuggested a role for ascorbate (AA) in suppressing uroporphyria inAA-requiring rats (in the absence of excess iron), the present studyinvestigated whether AA could suppress uroporphyria produced byexcess hepatic iron. Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of CYP1A2, and 5-aminolevulinic acid. Mice were administered either sufficient AA (1000 ppm) in the drinking water to maintainnear normal hepatic AA levels or a lower intake (75 ppm) that resulted in70% lower hepatic AA levels. The higher AA intake suppressed hepatic URO accumulation in the absence of administered iron, but not when irondextran (300-500 mg Fe/ kg) was administered. This effect of iron wasnot due to hepatic AA depletion since hepatic AA content was not decreased. The effect of iron to prevent AA suppression of hepatic URO accumulation was not observed until a high hepatic iron threshold was exceeded. At both low and high AA intakes, hepatic malondialdehyde (MDA), an indicator of oxidative stress, was increased three-fold by high doses of iron dextran. MDA was considerably increased even at low iron dextran doses, but without any increase in URO accumulation. The level of hepatic CYP1A2 was unaffected by either AA intake. Conclusion: In this mouse model of PCT, AA suppresses hepatic URO accumulation at low, but not high hepatic iron levels. These results may have implications for the management of PCT.
(HEPATOLOGY2007;45:187-194.).
------------
Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda. Hepatology. 2007 Sep 13; Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, Balestra D, Sinclair JF, Sinclair PR. Veterans Affairs Medical Center, White River Junction, VT.
Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used Hfe(-/-) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron- deficient diets. Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5- aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL/6 Hfe(-/-) mice treated with ALA and a CYP1A2 inducer. ALA- treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection. Conclusion: The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation. (HEPATOLOGY 2007.).
On Jul 30, 7:30 pm, ironjustice <ironjust...@rock.com> wrote:
"Mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria "
The whole thing is summed up by the bizarre finding above. The researchers **accidentally** found "something in that food is causing disease in our mice" and they switched to a chow they created **themselves** and found this new food .. which coincidentally .. **doesn't contain meat** .. didn't cause the disease NO MATTER HOW MUCH IRON WAS GIVEN TO THE ANIMALS.
> This is as close to a .. gauntlet .. we are going to get ..
> Somebody .. somewhere .. step up ..
> There's gotta be a man amongst .. ya ..
> We have established .. CONCLUSIVELY .. **they** have DECIDED amongst > themselves it would be "wise" to treat EACH AND EVERY ONE WITH LUPUS > with a drug which is EXCLUSIVELY to be used INSTEAD of > **bloodletting** .. but .. bloodletting has NEVER EVEN BEEN MENTIONED > in the treatment of lupus patients .. EVER .. ever ..
> Now either each and every lupus patient is .. stupid .. which is > obviously I guess .. and each and every medical person is stupid .. ?
> Or .. I .. am stupid ..
> This shows vitamin C .. normally .. can offset a slight buildup of > iron but WHEN the iron hits a 'certain level' the iron OVERWHELMS the > vitamin C's **ability** to OFFSET this higher iron and the body > cannot .. cope.
> "Ascorbate suppresses hepatic URO accumulation at low, but not high > hepatic iron levels"
> This shows when the iron gets to a 'certain point' .. BOOM ..
> "Was not observed until a high hepatic iron threshold was exceeded"
> It shows it can be controlled by targeting the iron with diet and / > or > DIRECT iron targeting.
> Uroporphyrin induces an autoimmune response / autoimmune like > response.
> Effect of iron and ascorbate on uroporphyria in ascorbate-requiring > mice as a model for porphyria cutanea tarda. > Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, > Balestra D, Sinclair JF, Sinclair PR > Hepatology. 2006 Dec 22; 45(1): 187-194
> Excess hepatic iron is known to enhance both porphyria cutanea tarda > (PCT) and experimental uroporphyria. > Since previous studies havesuggested a role for ascorbate (AA) in > suppressing uroporphyria inAA-requiring rats (in the absence of > excess > iron), the present studyinvestigated whether AA could suppress > uroporphyria produced byexcess hepatic iron. > Hepatic URO accumulation was produced in AA-requiring Gulo(-/-) mice > by treatment with 3,3',4,4',5-pentachlorbiphenyl, an inducer of > CYP1A2, and 5-aminolevulinic acid. > Mice were administered either sufficient AA (1000 ppm) in the > drinking > water to maintainnear normal hepatic AA levels or a lower intake (75 > ppm) that resulted in70% lower hepatic AA levels. > The higher AA intake suppressed hepatic URO accumulation in the > absence of administered iron, but not when irondextran (300-500 mg > Fe/ > kg) was administered. > This effect of iron wasnot due to hepatic AA depletion since hepatic > AA content was not decreased. > The effect of iron to prevent AA suppression of hepatic URO > accumulation was not observed until a high hepatic iron threshold was > exceeded. > At both low and high AA intakes, hepatic malondialdehyde > (MDA), an indicator of oxidative stress, was increased three-fold by > high doses of iron dextran. > MDA was considerably increased even at low iron dextran doses, but > without any increase in URO accumulation. > The level of hepatic CYP1A2 was unaffected by either AA intake. > Conclusion: > In this mouse model of PCT, AA suppresses hepatic URO accumulation at > low, but not high hepatic iron levels. > These results may have implications for the management of PCT.
> (HEPATOLOGY2007;45:187-194.).
> ------------
> Effect of an oral iron chelator or iron-deficient diets on > uroporphyria in a murine model of porphyria cutanea tarda. > Hepatology. 2007 Sep 13; > Gorman N, Zaharia A, Trask HS, Szakacs JG, Jacobs NJ, Jacobs JM, > Balestra D, Sinclair JF, Sinclair PR. > Veterans Affairs Medical Center, White River Junction, VT.
> Porphyria cutanea tarda is a liver disease characterized by elevated > hepatic iron and excessive production of uroporphyrin (URO). > Phlebotomy is an effective treatment that probably acts by reducing > hepatic iron. > Here we used Hfe(-/-) mice to compare the effects on > hepatic URO accumulation of two different methods of hepatic iron > depletion: iron chelation using deferiprone (L1) versus iron- > deficient diets. > Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5- > aminolevulinic acid (ALA), which results in hepatic URO accumulation, > and increasing doses of L1 in the drinking water. Hepatic URO > accumulation was completely prevented at low L1 doses, which > partially > depleted hepatic nonheme iron. By histological assessment, the > decrease in hepatic URO accumulation was associated with greater > depletion of iron from hepatocytes than from Kupffer cells. > The L1 treatment had no effect on levels of hepatic cytochrome > P4501A2 > (CYP1A2). > L1 also effectively decreased hepatic URO accumulation in > C57BL/6 Hfe(-/-) mice treated with ALA and a CYP1A2 inducer. ALA- > treated mice maintained on defined iron-deficient diets, rather than > chow diets, did not develop uroporphyria, even when the animals were > iron-supplemented either directly in the diet or by iron dextran > injection. > Conclusion: > The results suggest that dietary factors other than iron are involved > in the development of uroporphyria and that a modest depletion of > hepatocyte iron by L1 is sufficient to prevent URO accumulation. > (HEPATOLOGY 2007.).
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