![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 86 to 110 of 128. Go back in thread:
Posted by BarbaraCat on July 13, 2004, at 14:41:36
In reply to Re: Sounds like a question for CHEMIST! » BarbaraCat, posted by chemist on July 12, 2004, at 19:53:57
I realized after posting this that I made a serious gender blunder. You may be a Ph.D. (which you are), but here I am assuming you're a Mr., whereas nothing in your posts gives me reason to believe you are not a Ms!. No biggie, just amusing to catch myself hoisted on my own 'liberated' petard.
Thanks for your thorough replies to my and all of our questions. You are truly a blessing on this board and always so responsive. I speak for us all when I say we've learned much from you and you're a great asset.
I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning. The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.
The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.
So I will be busy with all my books and papers following the tail of methyl doners, histamines and into all the caverns and crannies this will lead me to. Any pointers would be appreciated. But mercy! I have some organic chemistry and neurobiology under my belt, but am by no means 'Mrs. Science'. Take care and thanks. - Barbara
> > Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat
>
> no, thank you (and the other posters), it's interesting and rewarding to delve into new areas (i speak of myself)...please do keep us informed about the methylation business...let me throw another bone your way: when doubly-protonated, the side chain carries a formal charge. from my work with alkaloids that bind to ligand-gated ion channels of a certain flavor, i know that the binding affinity is greatly increased if one protonates the compound in question. i wonder if a similar antagonism is instigated if the epsilon nitrogen is protonated, and thus competitive binding to H_{1} become more non-competitive? food for thought.........let us know what you discover.......and since you asked, it is chemist, Ph.D. (that and $2.00 gets me a cup of coffee.......).....all the best, chemist
> >
> >
> > > differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
> > >
> > >
> > > > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> > > >
> > > > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> > > >
> > > > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> > > >
> > > >
> > > > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > > > >
> > > > >
> > > > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > > > >
> > > > > > >
> > > > > >
> > > > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > > > >
> > > > > > Cheers,
> > > > > > Panda.
> > > > > >
> > > > >
> > > >
> > > >
> > >
> >
> >
>
Posted by chemist on July 13, 2004, at 15:02:31
In reply to Re: okay, here we go... (new cocktail) » chemist, posted by cpallen79 on July 13, 2004, at 12:13:49
> Hey Chemist,
> I went to my PDOC today! here's the new "cocktail" we are going to try.
>
> Luvox- probably get upt to around 200 MGS
> Trazedone- around 25 mgs
> Adderall XR- 5 mgs
> Ativan as needed
>
> I am reluctant to take ativan, but my PDOC is very concerned about my anxiety and agitation of course, both of have been major cornerstones of my depression. We've also discussed the posssiblity of using an anticonvulsant/mood stabilizer to help with anxiety and agitation. Lamitcal came up, I told her I'd consider it.... just gotta watch out for that pesky rash of course! :)
hello there, chemist here....the cocktail you describe looks promising. friend, do not fear the ativan: if you feel uncomfortable, use it. that's what it's there for. please keep us informed of how things are going, and i wish you all the best, chemist
Posted by chemist on July 13, 2004, at 16:30:11
In reply to Re: Sounds like a question for CHEMIST! » chemist, posted by BarbaraCat on July 13, 2004, at 14:41:36
hello there, you'll notice the title of this post. not too long ago, i referred to sad panda as ``he'' in a post, and another poster asked why i assumed that sad panda was a male. i replied that i didn't know, and i recall that panda was simply tickled by the whole question of he/she. as am i, honored to join San Panda as the subject of a gender inquiry. on another note, you sound like you know your stuff: are you a chemist, biologist, m.d., if you don't mind my asking? and please keep us informed on your digging into the histamine/histidine business, it is quite intriguing......all the best, cHEmist
> I realized after posting this that I made a serious gender blunder. You may be a Ph.D. (which you are), but here I am assuming you're a Mr., whereas nothing in your posts gives me reason to believe you are not a Ms!. No biggie, just amusing to catch myself hoisted on my own 'liberated' petard.
>
> Thanks for your thorough replies to my and all of our questions. You are truly a blessing on this board and always so responsive. I speak for us all when I say we've learned much from you and you're a great asset.
>
> I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning. The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.
>
> The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.
>
> So I will be busy with all my books and papers following the tail of methyl doners, histamines and into all the caverns and crannies this will lead me to. Any pointers would be appreciated. But mercy! I have some organic chemistry and neurobiology under my belt, but am by no means 'Mrs. Science'. Take care and thanks. - Barbara
>
>
> > > Thanks Mr. (or is it Dr.) Chemist! That gives me a whole bunch of info to keep me busy. Ties in with the under-over methylation theories as well. Much appreciated. - BCat
> >
> > no, thank you (and the other posters), it's interesting and rewarding to delve into new areas (i speak of myself)...please do keep us informed about the methylation business...let me throw another bone your way: when doubly-protonated, the side chain carries a formal charge. from my work with alkaloids that bind to ligand-gated ion channels of a certain flavor, i know that the binding affinity is greatly increased if one protonates the compound in question. i wonder if a similar antagonism is instigated if the epsilon nitrogen is protonated, and thus competitive binding to H_{1} become more non-competitive? food for thought.........let us know what you discover.......and since you asked, it is chemist, Ph.D. (that and $2.00 gets me a cup of coffee.......).....all the best, chemist
> > >
> > >
> > > > differing welcomed and addition information insightful.....i'm just a chemist, remember...i will point out (you know i always have to point something out.....) that it is H_{1} that is hit hardest by seroquel, and (stealing from my PDR) of all the receptors it hits, the IC_{50} for H_{1} is the lowest (!!!), at 30 nM, so no wonder the sedation. a few comments on histidine/histamine. the process of decarboxylating histidine is undertaken by an enzyme that more or less depends on your intake of vitamin B6. also, histidine at physiological pH can be protonated at both the delta and epsilon nitrogens, although the delta form dominates. there might be some correlation in your (i am using the collective ``your'') biochemistry (including stomach acids, lest we forget) that favors the doubly-protonated form and thus the production of a histamine (assuming it stays doubly-protonated after decarboxylation by PLP-powered enzymes) is deficient. alternatively, you might - and i need Larry's help here, so please page him - somehow be overproducing b6, thus making more histamine than ``normal,'' and any introduction of additional histamine will hit you like a brick. enough. all the best, chemist
> > > >
> > > >
> > > > > Must respectfully differ with you, Most Esteemed Chemist, but I don't think it has to do with too small a Seroquel dose and breakthrough anxiety. I had an experience similar to Chris' with Seroquel just last week and a few years back with Zyprexa. Was doing pretty darn good on lithium and pharmaceutical St. John's Wort and decided to go with Seroquel mainly for sleep and any additional benefits an AP might provide for my mixed-states bipolar bane.
> > > > >
> > > > > Took 12.5mg/night for 4 nights and it was like I woke up on the far side of the Styx after the first dose. Agitated woozy weepy dysphoric clumsy hell. Plus a very uncharacteristic lust/frenzy for anything that hinted of cake or cookie. Kept expecting it to get better but it was getting worse. And I gained 5 lousy pounds for the priviledge.
> > > > >
> > > > > I realize that 12.5mg is more sedating than higher doses and this dysphoria might have eventually gone away, but the point is that something hit hard and very quickly. A very rapid switch into agitated depression and total relief after stopping. What jumps out at me is histamine. For one, the groggy sedation felt much like an anti-histamine, plus I understand that unbalanced histidine and therefore histamine levels have been implicated in depression. Mainly H3, and Seroquel seems to target H1 but jeez, mere technicalities. Perhaps I'm one of those 'histadelics' (it does feel like hysterical psychedelics for that matter). Perhaps methylation is a factor. I dunno. I only know that something caused this rapid switch into dysphoric agitation. There's a profound clue waiting to be discovered here. Just hope I don't have to go through any further personal testing to find out. I welcome any and all thoughts. - Barbara
> > > > >
> > > > >
> > > > > > ahhh, the buck has been passed....thank you, panda...remind me not to play poker with you next time i'm down under.....the answer to the post is that, in my opinion, the seroquel dose was too small (i have to read the next one, so don't hold to this just yet) and it sounds like breakthrough anxiety. that said, i still think panda's answer is better than mine in that maybe yes, maybe no (what dose?) and what other drugs are on board that can inhibit/induce/act as substrates for isoenzymes that are also part of the seroquel metabolic route. see, i told you panda's the expert.....on to the next post, where i believe i glimpsed the meds list.....see you there, all the best, chemist
> > > > > >
> > > > > >
> > > > > > > > Hi Panda, I was taking a tiny dose of Seroquel for sleep and a dab during the dayfor anxiety. I did well at first, but then after about a week I became very very restless and my anxiety levels really increased. Was this akathisia? I stopped takign the Seroquel Saturday but still have not felt well, what in the world happened?
> > > > > > > >
> > > > > > > >
> > > > > > >
> > > > > > > Possibly, Akathesia is said to be a feeling of inner agitation which makes you fidgety & unable to sit still. Perhaps there was a drug interaction involved? Some drugs can raise the levels of other drugs & vice versa if they share the same liver enzyme. It's an ideal question for Chemist. :)
> > > > > > >
> > > > > > > Cheers,
> > > > > > > Panda.
> > > > > > >
> > > > > >
> > > > >
> > > > >
> > > >
> > >
> > >
> >
>
>
Posted by KaraS on July 13, 2004, at 17:43:30
In reply to i got Panda-ed!!! » BarbaraCat, posted by chemist on July 13, 2004, at 16:30:11
Posted by KaraS on July 13, 2004, at 20:10:21
In reply to i got Panda-ed!!! » BarbaraCat, posted by chemist on July 13, 2004, at 16:30:11
BarbaraCat, I am the one who initially "Panda-ed" Chemist by bringing up the same issue that you did. Like you, I found myself making assumptions about the gender of various posters without justification. I love the way you described it: "hoisted on my own 'liberated' petard". That's perfect!
At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
KaraS
Posted by BarbaraCat on July 14, 2004, at 11:44:09
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 13, 2004, at 20:10:21
> At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
>
**Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.
Posted by cpallen79 on July 14, 2004, at 12:46:26
In reply to Re: BarbarCat, i got Panda-ed!!! » KaraS, posted by BarbaraCat on July 14, 2004, at 11:44:09
> Ditto! I hope he comes back!!! I can't imagine not having chemist around!
> > At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
> >
> **Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.
>
>
>
Posted by KaraS on July 14, 2004, at 15:46:06
In reply to Re: BarbarCat, i got Panda-ed!!! » KaraS, posted by BarbaraCat on July 14, 2004, at 11:44:09
>
> > At any rate, I just thought I'd let you know that after his most recent post, Chemist won't be adding any new posts here for a week as he's just been banned from posting by Dr. Bob (for an unrelated matter).
> >
> **Oh, that's too bad! He was being really helpful to me in my med questions quest. Well, at least I know he's a 'he'. Not that it makes any difference. Thanks for letting me know why I won't be hearing from him.
>
>
>A week really isn't that long and I'm sure he'll be back as soon as he can (knowing him) and will pick up where he left off.
Posted by karen_kay on July 14, 2004, at 22:19:12
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 14, 2004, at 15:46:06
hey all! i've been dumpster diving (archiving as you commoners call it) and i found chemist's email addy (in case anyone wants to keep in touch). i email him and he always returns his emails (sometimes he blows kisses too, but only if you're very very nice :)
it's todd at lanczos dot cm dot utexas dot edu
the link for his email addy ishttp://www.dr-bob.org/babble/20040712/msgs/365398.html
(ha, did you think i was lying? not this time :)
he hangs out in open sometimes (but only if you're very, very lucky (wait, is it very, very unlucky? your choice i suppose..))
tootles..... i'm sure he'd like some company while he's in solitary confinement...
kk
oh, and you've been kk-ed, i'm a she!!! (though i noticed there's another kk floating around here somewhere.. i'll have to catch up with that person... this could get very interesting folks.. keep your eyes open!
Posted by KaraS on July 15, 2004, at 1:44:12
In reply to Re: BarbarCat, i got Panda-ed!!! » KaraS, posted by karen_kay on July 14, 2004, at 22:19:12
You are too funny, kk (the real/original kk)!! Thanks for Chemist's address. I'll have to drop him a line. He knew his exile was coming but he fought the good fight anyway. I also hope he can survive his solitary confinement for the week.
I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)
Take care,
Kara
Posted by BarbaraCat on July 15, 2004, at 9:41:36
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 15, 2004, at 1:44:12
Texas! That's a kick! Can't you just imagine Chemist with a Texan Twang? That is too precious. I thought he was Aussie. Hey Chemist, you're missed! - BCat
>> I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)
>
> Take care,
> Kara
Posted by Racer on July 15, 2004, at 12:27:46
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by BarbaraCat on July 15, 2004, at 9:41:36
Hey, BararaCat - chemist asked me to post his email to you, since he can't respond here. Taken from a thread below:
todd at lanczos dot cm dot utexas dot edu
(I'm guessing the "dot cm" is actually "dot com")He is missed. He really is an asset to our community here. Still, it's only a week...
Posted by cpallen79 on July 15, 2004, at 12:30:58
In reply to Re: BarbarCat, i got Panda-ed!!! » BarbaraCat, posted by Racer on July 15, 2004, at 12:27:46
I miss Chemist too, he really is an asset to us, tell him I say hi!
Posted by Racer on July 15, 2004, at 14:58:51
In reply to Re: BarbarCat, i got Panda-ed!!! » BarbaraCat, posted by Racer on July 15, 2004, at 12:27:46
Posted by KaraS on July 15, 2004, at 16:32:39
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by BarbaraCat on July 15, 2004, at 9:41:36
> Texas! That's a kick! Can't you just imagine Chemist with a Texan Twang? That is too precious. I thought he was Aussie. Hey Chemist, you're missed! - BCat
>
I can't imagine him with a Texan twang at all either. Maybe he just moved there from somewhere else (like Britain or Australia) for work purposes. I need to keep reading his posts with a British accent so I think I 'll stick with that theory!Yes, you are missed Chemist!!!
-K
> >> I never figured that he lived in Texas. Somehow I had the idea that he was British. (He'll probably get a good laugh out of that one.)
> >
> > Take care,
> > Kara
>
>
Posted by Sad Panda on July 15, 2004, at 17:44:29
In reply to Re: BarbarCat, i got Panda-ed!!!, posted by KaraS on July 15, 2004, at 16:32:39
Chemist is sorely missed, he always seems to have the facts. :(
If it helps, imagine that Chemist sounds like George W. :D
Cheers,
Panda.
Posted by KaraS on July 15, 2004, at 19:05:37
In reply to Re: BarbarCat, i got Chem-ed!!!, posted by Sad Panda on July 15, 2004, at 17:44:29
> Chemist is sorely missed, he always seems to have the facts. :(
>
> If it helps, imagine that Chemist sounds like George W. :D
>
> Cheers,
> Panda.
>He's the last person in the world I'd like to think that Chemist sounds like!!!
- Kara
Posted by Dr. Bob on July 15, 2004, at 19:27:38
In reply to Re: BarbarCat, i got Chem-ed!!!, posted by KaraS on July 15, 2004, at 19:05:37
Posted by Larry Hoover on July 18, 2004, at 11:23:45
In reply to Re: Sounds like a question for CHEMIST! » chemist, posted by BarbaraCat on July 13, 2004, at 14:41:36
> I am going to be delving into methylation land for the next bit. There is a common thread that's appearing to all this, first with the histamine hypothesis and the tie with with possible methyl doner malfunctioning.
Easy enough to supplement to target methyl donation.....betaine and B-12.
> The reason it jangled my bells is that I had a serious reaction to Lamictal all the while I was taking it and eventually stopped. Stevens Johnson developed from taking DMPS, a heavy metal chelator with a high affinitiy to thiol groups (in my case trying to chelate mercury) so there could be a possible tie in with the histimine/methylation relation, if there is one, and a possible breakdown of sulfur/thiol metabolism.
DMPS has a substantial impact on all metal cations. If I recall correctly, it is about 30 times more effective at removing zinc than mercury. Serious business, using chelation therapy. All too often, it is poorly managed, from a medical perspective. If mercury is a potential toxicant, take selenium. It will covalently bond to the mercury, totally inactivating it. The solubility constant for Se-Hg is on the order of ten to the -70. In other words, you would require roughly 10 to 46th power litres of water to dissolve one molecule. In other other words, it is so insoluble that its solubility can't be measured. The mercury will stay in your body, but it will be totally inert.
Thiol/sulphur metabolism is absolutely disturbed in fibromyalgia. That's why I've been pushing taurine. It's the sulphonic acid version of GABA.
> The other clue is that I have fibromyalgia and some recent studies have identified a epithelial mast cell inflammatory involvment which may account for the heightened skin nerve pain response. But also, ta-da, a malfunctioning histamine response at skin receptor sites seems to be involved, which would predispose one towards an inflamed skin pain sensitivity but also a heightened alergic response resulting in the erythema multiforme 'rash' (which is a severe separation of mast cells from the epithelial substrate). Mast cells -> histimine. There it is again.Niacinamide down-regulates histamine synthesis, and also blocks mast-cell degranulation (histamine release). It also, coincidentally, is an agonist at GABA receptors.
FASEB J. 2003 Aug;17(11):1377-9.
Nicotinamide: a potential addition to the anti-psoriatic weaponry.Namazi MR.
Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran. namazi_mr@yahoo.com
Psoriasis is an inflammatory disorder characterized by a T helper type 1 cell cytokine pattern. Increased expression of adhesion molecules, prominent neutrophil accumulation, and increased production of nitric oxide are characteristics of this disorder. Moreover, histamine and proteases are supposed to participate in the pathogenesis of psoriasis. Nicotinamide is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) that, through enhancement of nuclear kappa B-mediated transcription, plays a pivotal role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Through interaction with CD38 and inhibition of IL-1, IL-12, and TNF-alpha production, nicotinamide produces a mild TH2 bias. Nicotinamide is a potent phosphodiesterase inhibitor and suppresses neutrophil chemotaxis and mast cell histamine release. It inhibits nitric oxide synthase mRNA induction and suppresses antigen-induced lymphocyte transformation. Nicotinamide increases the biosynthesis of ceramides, which upon degradation produce sphingosine. Sphingosine inhibits protein kinase C (PKC) and decreases basal cell proliferation dependent on PKC. Taken together, it can be reasoned that nicotinamide could be a useful addition to anti-psoriatic armamentarium. The combination of nicotinamide and thalidomide or methotrexate provided a powerful synergistic inhibition of murine collagen-induced arthritis. Nicotinamide decreased the methotrexate-induced hepatotoxicity. The above combinations may prove to have a powerful anti-psoriatic effect as well. As PARP inhibitors could exert anti-retroviral effect, nicotinamide could also be of special value in the treatment of HIV-infected psoriatics.
I expect this topic to be redirected, but I hope that a greater audience is exposed to some of these concepts, here on the main Babble board. Alternative medicine is drug-augmentative. There's a lot more you can do than get prescriptions filled.
Lar
Posted by BarbaraCat on July 18, 2004, at 17:19:22
In reply to Re: Sounds like a question for CHEMIST! » BarbaraCat, posted by Larry Hoover on July 18, 2004, at 11:23:45
Ah, Larry, you are amazing. You've been away and you have been missed! I wish I could make an appoinment with you. You've given me more info tha 20 doctors I've been to in the last 2 years. I'm a little wary of going the methyl doner path since I seem to fit the histademia model, which spells high-methylation. I feel like I'm in a vice with my vitamin bottles. Oh, and I have high iron levels as well and Vitamin C recirculates iron, so can't take C. Taurine is about the only thing I trust. Something's going on with my metals metabolism. Maybe it has to do with low zinc, B6. But if not, if I over produce B6 I could get into trouble. Perhaps my toxic load of mercury is at the heart of everything.
I'll be going to a functional MD this week for some major testing in this area. But I'd be surprised if he mentions using selenium for mercury inactivation since his lab is filled with people hooked up to chelation IV lines. I've learned my lesson in that area - no chelation for me. It gets so disheartening when it starts dawning that every one of these 'healers' we desperatly seek out are in it to extract our money.
I am so discouraged, depressed, and angry. I go about life just fine, start making plans, taking classes, getting a life back again. And bam! I'll wake up totally in pain, fatigue, can't sleep, stiff, depressed, befuddled. I can't figure this thing out and feel like I'm spinning my wheels and spending money I don't have on my meagre disability earnings.
I don't care if this gets redirected to whatever category it rightly fits into. If this were you, Larry, what would you do? What supplements would you take, what doors would you pound on, who knows anything? Thanks you bearing with me during this outpouring. It helps. - Barbara
Posted by Larry Hoover on July 19, 2004, at 10:51:31
In reply to Re: Sounds like a question for CHEMIST! » Larry Hoover, posted by BarbaraCat on July 18, 2004, at 17:19:22
> Ah, Larry, you are amazing. You've been away and you have been missed! I wish I could make an appoinment with you. You've given me more info tha 20 doctors I've been to in the last 2 years.
Oh, my. I don't know what to say. thanks
> I'm a little wary of going the methyl doner path since I seem to fit the histademia model, which spells high-methylation.
You're using Pfeiffer's categories, I take it. Two things about the thinking processes involved. Invoking a model makes comprehension simpler because a model invariably leaves out information. The danger lies in treating the model as if it is a real entity (that's called reification). The second thing is that the lines between any such categorization system are arbitrary. Mother Nature herself does not draw such lines. Few people would fit nicely into those abstract pigeon-holes. Most will straddle the lines, no matter where they are placed.
> I feel like I'm in a vice with my vitamin bottles. Oh, and I have high iron levels as well and Vitamin C recirculates iron, so can't take C.
Your serum ferritin is high? You have hemochromatosis? The answer is blood-letting, not vitamin C avoidance.
> Taurine is about the only thing I trust.
I trust taurine, too. Moooooooo.
> Something's going on with my metals metabolism. Maybe it has to do with low zinc, B6.
The metals are a toughy. Different tissues have vastly different concentrations, and also ratios of concentrations. You mentioned chelation....if you had that, without receiving IV mineral reconstitution, it's little wonder your metals are messed up.
> But if not, if I over produce B6 I could get into trouble.
I wouldn't worry in the least about too much B6. Really. It would fix your sulphur problem. And you don't produce B6. We take it in its provitamin form, in supplement pills. It's not active as pyridoxine. Your liver has to phosphorylate it, to P-5-P. Then it becomes more reactive, and it can participate as a cofactor in enzymatic reactions.
> Perhaps my toxic load of mercury is at the heart of everything.
Mercury is probably the worst commonly found toxicant in existence. Its net effect is to substantially increase oxidative stress. Oxidative stress is a general, non-specific effect, which targets anything vulnerable to oxidation. Guess what those things might be. High on the list are polyunsaturated fatty acids. Even higher on the list are thiols. At about the same level is DNA, but the latter has better protection than e.g. cell membranes or thiol-containing proteins.
> I'll be going to a functional MD this week for some major testing in this area. But I'd be surprised if he mentions using selenium for mercury inactivation since his lab is filled with people hooked up to chelation IV lines. I've learned my lesson in that area - no chelation for me. It gets so disheartening when it starts dawning that every one of these 'healers' we desperatly seek out are in it to extract our money.
It seems so, doesn't it?
> I am so discouraged, depressed, and angry. I go about life just fine, start making plans, taking classes, getting a life back again. And bam! I'll wake up totally in pain, fatigue, can't sleep, stiff, depressed, befuddled. I can't figure this thing out and feel like I'm spinning my wheels and spending money I don't have on my meagre disability earnings.I can't even afford some of my own ideas. Ya, I understand that issue. I know of exactly what you describe.
> I don't care if this gets redirected to whatever category it rightly fits into. If this were you, Larry, what would you do?One thing I would do, is to take a deep breath. Then another one, and so on, until the feeling passes.
> What supplements would you take, what doors would you pound on, who knows anything? Thanks you bearing with me during this outpouring. It helps. - Barbara
Have you ever read the articles by Dr. Pall? His links aren't working at this moment, for some reason, but... http://molecular.biosciences.wsu.edu/Faculty/pall.html
He's developed a unified theory that relates chronic oxidative stress to the symptoms of fibromyalgia, chronic fatigue and PTSD, along with biochemical markers for these. He also corresponded with me a couple years back, and gave me some dietary recommendations. Unfortunately, those emails are on a malfunctioning computer, and I haven't been able to get the bugs out to access the data, yet.
I hope you gain some assurance from the fact that you do not walk this path alone.
Lar
Posted by BarbaraCat on July 19, 2004, at 11:28:23
In reply to Re: Sounds like a question for Lar! » BarbaraCat, posted by Larry Hoover on July 19, 2004, at 10:51:31
Thanks, Larry. Feeling a lot better today. Those fibro flares are the pits, although I was able to sustain more hope during it than with others. Yes, I was referring to Pfeiffer's classifications, which I don't take as Gospel. A bit too pigeon-holey, plus I haven't heard much in the way of success with depression or bipolar disorders from their clinic.
The link didn't work, as you said. Anything you can dig up in the future would be appreciated. I know how it goes with a clobbered computer. My laptop was invaded by a scum-ware worm over the winter and it took 3 weeks of non-stop little-sleep damage control. Felt like invasion of the body snatchers. A good lesson in keeping virus definitions up to date.
In the meantime, I'll do a search with his name and other combinations of 'oxidative stress'+fibromyalgia. I'll let you know how the Functional MD visit and tests go if you'd like. Take care. - Barbara
Posted by Larry Hoover on July 19, 2004, at 11:41:10
In reply to Re: Sounds like a question for Lar! » Larry Hoover, posted by BarbaraCat on July 19, 2004, at 11:28:23
> In the meantime, I'll do a search with his name and other combinations of 'oxidative stress'+fibromyalgia.Pall's work centers on peroxynitrite. That will focus the search, using that keyword.
> I'll let you know how the Functional MD visit and tests go if you'd like.
Please.
> Take care. - Barbara
And you,
Lar
Posted by BarbaraCat on July 19, 2004, at 12:26:16
In reply to Re: Sounds like a question for Lar! » BarbaraCat, posted by Larry Hoover on July 19, 2004, at 11:41:10
My search pulled up quite a few very relevant hits. Very very interesting. Good fuel for my upcoming visit. Thanks again, Lar. - Barbara
Posted by tepiaca on July 20, 2004, at 2:11:49
In reply to Re: Sounds like a question for CHEMIST! » BarbaraCat, posted by Larry Hoover on July 18, 2004, at 11:23:45
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