tini vs metro

I havent ever looked into the tinii vs metro issue much. I just started tini and it did great things for me so I stuck to it. So I'm not out to broadly say tini is better when I share the following quote, just wanted to make a note of it:

"Jokipii et al [reference] reported and average CFSi to serum ration of 0.43 in patients given 2.4 g of metronidazolei orally; corresponding ratio after 2 g of tinidazole was 0.88."

Journal Title: Scand J Infect Dis Suppl
Volume: 26
Year: 1981
Inclusive Pages: 60-67
Article Title: Pharmacokinetics of nitroimidazoles.
Spectrum of adverse reactions.

I just happened to run across this. I dont know whether workers confirmed or disconfirmed these numbers.

I am switching to Tinii with my next pulse.  I hope that I will get less nausea and better tolerance as well as better levels.

Interesting materialthank oyu for posting this! I am using tinii as of this pulse #7 and it was great. Muchbetter! I'm glad to know that it has apparently good CNSi penetration
marie

On CAPi since Sept '05 for MSi, RAi, Asthmai, sciatica. EDSSi at start 5.5.(early cane) Now 6 (cane full time) Originally on: Doxyi 200, Azith 3x week, Tinii cont. over summer '07, Revamp of protocol in Summer '08 by Stratton due to functional loss; clarithro

I was planning to begin with flaygl, can I choose tinii to start or is this not recommended?

5oo mgs Ceftin 2 x/day, 500 mgs Zithromax, 500 mgs 2 x tinii pulses,100 mg diflucan, 4.5 ldni; Wheldon protocol for MSi April, 2006 to May 2008. 2008 MRI shows NO NEW DISEASE ACTIVITY, 2012 MRI no new disease activity.

Oh sure it is as good by DrWheldon's assessment. I certainly having done both would do the tinii. Marie

On CAPi since Sept '05 for MSi, RAi, Asthmai, sciatica. EDSSi at start 5.5.(early cane) Now 6 (cane full time) Originally on: Doxyi 200, Azith 3x week, Tinii cont. over summer '07, Revamp of protocol in Summer '08 by Stratton due to functional loss; clarithro

I am always looking for the most efficeint way to reduce the Cpni load and I have to admit the story for Tinidazole is pretty compelling with greater tissue penetration, higher serum concentration, lower side effects (according to people here), and presumably pretty much identical mechanisms of actions. I guess I will be switching soon too...

- Paul 

Tinidazole has been available in Europe for 25 years, but was only licensed in the US late last year.  Why this time difference I don't know.  However, even in the UK physicians, being largely a conservative lot, have preferred to stick with what they know.  I had to plead with David to give me a prescription of tinidazole.  My GP probably wouldn't have because of the greater cost: it is not yet out of patent......Sarah
Completed Stratton/Wheldon regime for aggressive secondary progressive MSi in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

I remember Chuck Strattoni's reaction when I told him what I was paying for Tinii-- even with some prescription insurance coverage-- vs what he says Flagyli is available for in bulk (dirt cheap). He was a bit shocked. But to me worth every penny given the nausea is mild compared to Flagyl for me, and it's only taken every two weeks. If you tolerate the Flagyl without side effects-- nausea, depression seem to be the worst ones-- then I'd say stick with it. It's cheap and effective.

On CAPi's protocol for Cpni in CFSi/FMSi since December 2004.
Currently: 150mg INHi, Doxyi/Zithi, Tini pulses 

"I really didn't say everything I said." Yogi Berra

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

I think Colonel Chuck is built from sterner stuff than a lot of us, and as he said, in bulk, flagyli is dirt cheap.  I don't think there is any way my GP would have given me an NHS prescription for tinidazole, since I am already pushing my luck with roxithromycin versus azithromycin.  I would now not want to go back to flagyl, never mind the cost.

 

Wiggy, as ADC Longlands, I would like to say there is no reason why you shouldn't start on tinidazole, but you haven't been on abxi for very long yet: don't rush into this stage too quickly, will you?

Sarah

Completed Stratton/Wheldon regime for aggressive secondary progressive MSi in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

Thanks for all the responses.

Sarah, I am not planning to start flagyli or tinii until last week june - I was going to wait until July but will go up north in July and want to feel ok.  I will see what my GP wants to do as far as which drug she wants to put me on.  Again, it is nice to have options.  Tini seems better tolerated from the opinions on the board but everyone is different.

This will be first week of zithromax for me :)

 

5oo mgs Ceftin 2 x/day, 500 mgs Zithromax, 500 mgs 2 x tinii pulses,100 mg diflucan, 4.5 ldni; Wheldon protocol for MSi April, 2006 to May 2008. 2008 MRI shows NO NEW DISEASE ACTIVITY, 2012 MRI no new disease activity.

Ah, Sarah, I'd always wondered why you wore that aiguillette.
D W - [Myalgia and hypertension">i (typically 155/95.) Began (2003) taking doxycycline and macrolide and later adding metronidazolei. No medication now. Morning BP typically 110/75]

Its not true!  I might come from an army background, but how would I paint in this?

 

 

 

Completed Stratton/Wheldon regime for aggressive secondary progressive MSi in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

My goats love my aiguilettes and I don't paint, but I will go along with the big switch to tinii, probably this coming weekend.

Rica 

Ignorance is voluntary bad luck.  Lauritz S.   A true Viking
If you come to a fork in the road, take it. Yogi Berra

3/9 Symptoms returning. Began 5 abxi protocol 5/9 Rifampin 600, Amox 1000, Doxyi 200, MWF Azith 250, flagyli 1000 daily. Began Sept 04 PPMSi EDSSi 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

Rica, my experience of goats is rather more limited than yours, but do try to keep them away from your dress uniform, because they love the braid. 

As a teenager I was once followed around  Longleat Safari park by a goat intent on nibbling the fringe around the hem of my jacket.  It was very adept at this and I didn't see the damage until it was too late.  It was quite a tall goat.

I shall await with baited breath to see how you get on with tinidazole........Sarah

Completed Stratton/Wheldon regime for aggressive secondary progressive MSi in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

Goats use their lips as we use our fingers and they want to know all about everything.  It really is a good thing they don't have fingers or we would be in big trouble.

Rica 

Ignorance is voluntary bad luck.  Lauritz S.   A true Viking
If you come to a fork in the road, take it. Yogi Berra

3/9 Symptoms returning. Began 5 abxi protocol 5/9 Rifampin 600, Amox 1000, Doxyi 200, MWF Azith 250, flagyli 1000 daily. Began Sept 04 PPMSi EDSSi 6.7 Now good days EDSS 1 Mind, like parachute, work only when open. Charlie Chan  In for the duration.&am

Here is a further consideration. Metro weighs 171 g/mol. Tinii weighs 247. So when you take one gram of metro, youre eating 1.44 times more molecules than you are eating in one gram of tini. Its the number of molecules that matter, rather than the weight.

However, the activity of the molecule is also important. To describe exactly how so we would have to know what happens when our microbes face nitroimidazoles. Unfortunately, we dont. The unusual observation is that only a small percentage of ones microbes are killed during each day of nitroimidazole use. How strange that is. Why should organisms that didnt die of yesterdays pulse (or in my case yesterdays dose, as Ive used tini more continuously), suddenly die of todays? Could it be that the deaths occur due to erroneous SOS repair of nitroimidazole damage to genesi vital for sustaining the cells life in the hostile host environment? Perhaps, but that sounds rather round-about. It may not be quantitatively realistic.

A related question: does programmed cell deathi play any role in the deaths of our bacteria? It used to be thought that unicellular organisms had no death program. Why should a unicellular organism kill a cell that is by definition its entire self; after all killing yourself never increases your fitness. But then it was realized that bacteria arent really unicellular organisms. In the Darwinian sense (the only sense that matters biologically) they certainly form "organisms" with other identical individuals - cells in their clone that have identical genomes. Behavior that increases the reproduction/persistencei of co-clonal cells should be as favored by evolution as behavior increasing the reproduction/persistence of the self. Therefore, it shouldnt be a great shock that killing of Blastocystis homonis by metronidazolei shows apoptotic features like directed DNA fragmentation: mic.sgmjournals.org/cgi/content/full/150/1/33. As Kim Lewis has pointed out, microbe clones may benefit from genes that increase clonal fitness at the expense of individual cells. If so it would be vital that such genes not be mutated in any cell, because their loss would cause the cell to behave unregulatedly. The clone (the mircrobial "organism") would then essentially have a cancer - a cell mass acting against the organismal interest. Thus, microbes might have apoptosis in order to protect themselves against "cancer."

Such a programmed death might be set off by DNA damage, which of course will be mutagenic. But is the programmed death essential or superfluous to metronidazoles action on B. hominis? Would the cells die anyway at the same metronidazole concentration even if no programmed death pathways were activated?

How precious little we really know about the action of antimicrobials...

Anyway, getting back to nitroimidazoles, in trichomonads, one group finds its steric factors of the drugs interaction with the radicalizing ferredoxins that govern the rate of radicalization (activation) of the drug. However it may be that these drugs kill microbes in fine, its likely that a higher rate of drug activation inside the target organism is better. According to this paper, greater bulk of the N substituant is deleterious to activation of nitroimidazoles by both Trichomonas vaginalis (a protozoan) and Anabaena, a cynobacterium: http://www.pubmedcentral.gov/picrender.fcgi?artid=149022&blobtype=pdf< 

Thus, it might be expected that metronidazole would be somewhat more active against these organisms, all else being equal, than tinidazole, with its larger N-substituant chain. Yet this appears to be true in only some cases:

http://www.pubmedcentral.gov/pagerender.fcgi?artid=172117&pageindex=2<

On the other hand, this paper examined a large series of nitroimidazoles in Giardia, Trichomonas, and Entameba, and found that electronic, not steric, factors (resonance conjugation) figured in the activity level of the molecule - tho very imperfectly:

http://aac.asm.org/cgi/content/full/43/1/73?ijkey=3e0fc9f817fe466c434dbceae8b838d9bf36b146<

If only we knew what enzymes in our infectionsi are responsible for nitroimidazole activation, this sort of analysis might be worthwhile.

The more questions which come up about the treatment variations, eg. metronidazolei vs tinidazole, amoxi vs NACi, the more I think there is call for getting at least a basic Cpni lab going at Vanderbilt again. The clinical questions on this could be tested rather readily via in vivo and in vitro comparisons of effect. The mechanisms of action and bacteria/agent interaction questions are important in the longer run, as we seek to find new more effective agents in this fight, or suppressive agents that don't have the cost in die-off symptoms.

The question of what causes the post-pulse reactions, when putatively the agent or it's metabolites should technically be out of the blood stream by then (although I'm not sure this has been measured much past a day or two in by the drug companies) is still open. Is there loading into fat or other tissues that comes to be metabolized a little slower? Is it apoptosis of cells previously inhibited from natural cell deathi? Is it cytokinei reaction to promote immunei clean up? Is it clearance of immune cells themselves so that there is a burst of immune activity and subsequent die-off? These are the current speculations out there.

What we do know is that the post-pulse phenomenon is quite real for many, and a common enough report to warrant warning and encouragement so people don't think the treatments making them worse. It's not until you get past the post-pulse reactions that you feel what improvements you got from the last round. 

On CAPi's protocol for Cpn in CFSi/FMSi since December 2004.
Currently: 150mg INH, Doxyi/Zithi, Tini pulses 

"I really didn't say everything I said." Yogi Berra

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

The unusual observation is that only a small percentage of ones microbes are killed during each day of nitroimidazole use. How strange that is. Why should organisms that didnt die of yesterdays pulse (or in my case yesterdays dose, as Ive used tinii more continuously), suddenly die of todays? Could it be that [yada yada yada]

Theres one interesting possibility I wasnt thinking of when I wrote this long spiel. It comes from DA Mitchison, the wiliest inquisitor into bacterial dormancy ever to hang out on earth. Mitchison generated data implying that the very long treatment time required to prevent relapse of tuberculosis is due to a minute subpopulation of dormant bacilli. Further, he has suggested that the dormant bugs may alternate between long periods of extreme hypometabolism, and short bursts of more normal levels of metabolic activity - bursts which may render them more vulnerable to antibiotic killing.

This is an intriguing possible model for what we see: bacterial loadi apparantly going down very, very slowly - which as I noted before, carries the peculiar implication that bugs which blithely shrugged off ones first 10 flagyli pulses all of a sudden die of the 11th pulse. Clearly some cumulative and/or fluctuating process(es) must be reponsible for these changes in their vulnerability status. If we could understand this, perhaps it could be exploited.

Eric- I really appreciate your questions and thoughts about this. In the back of my mind was a much more vague and less articulate version, more like "Why the hell does this take so long?" Your much more specific "Why does a dose which should kill all of them each time only kill some, some of the time..." sort of thing is much more cogent!

My thoughts have been along the lines of the multi-phase nature of the beast: if you don't catch it in the phase the drug effects you are, as Mike Powell says, "Just pushing them around from phase to phase." Stratton's rule: that the optimal bang is where you have an agent (or even more than one) for each phase fits this one too. 

Putting my labrat ear tag on: based on my experiments (now done with!) in high dose pulses, eg my last one was 2 days of 2 grams each day, I think there's also the issue of differential tissue concentrations. While adequate blood levels of killing concentration (MIC) can be acheived, that doesn't mean every tissue gets that concentration. I had reached a point on my regular Tinii pulses where I had little to no knee and sacroiliac joint pain during and after the pulses. But that last high dose pulse evoked knee and sacroilliac pain, and for days after, as well as other places where inflammatory pain had been diminishing. Surprised me how much. I thought I had cleared those tissues already.

Chuck Strattoni told me that the first case he was called on to consult about, which got him started on the whole Cpni thing, was a case of resistant anemia where eventually they were able to culture Cpn from the bone marrow!  I think about that (and the smarts it must have taken to make the connection to infection by a respiratory pathogen for God's sake) when I think about where this bug can hide out, and what it takes to reach it in terms of drug concentration or sheer stubborn, persistant treatment.

On CAPi's protocol for Cpn in CFSi/FMSi since December 2004.
Currently: 150mg INHi, Doxyi/Zithi, Tini pulses 

"I really didn't say everything I said." Yogi Berra

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Eric, assuming [and hoping] this theory is true, the aftermath of my most recent pulse demonstrates that this time 'round, the bugs were vulnerable...very vulnerable.

"What saves a man is to take a step.  Then another step"

-C.S. Lewis

Wheldon Protocol for rrmsi since Oct '05.  Added LDN 4.5mg qhs Oct '07.  All supp's.  Positive IGGi's for Lyme Disease,Babesia, & Erlichiosis Sept. 2008.  Currently:  Mepron 750mg bid and Azithromycin 250mg qdi for Babesia.

"Be afwaid..."

KK2- Somehow your statement evoked for me and image of you facing off your Cpni (kind of a cartoon beastie in my fantasy), with you shaking your finger and saying:

    "Be afwaid, be vewy, vewy afwaid..."

On CAPi's protocol for Cpn in CFSi/FMSi since December 2004.
Currently: 150mg INHi, Doxyi/Zithi, Tinii pulses 

"I really didn't say everything I said." Yogi Berra

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Looking at David Wheldoni's diagram on "CPNi Simple" (Hey, draw me a picture!), it seems like:

 Protein synthesis inhibitors must not be 100% effective, neither in forcing reticulate bodies into cryptic bodies, nor in stopping protein synthesis. If they were, the synthesis of HSPi-60 would cease, the cell would die normally, and the C.Pn. inside it would die as well. On the other hand, the host cells lysosomes must get a few of the beasties, or we'd die.

There must be some minimum production of HSP-60 and other 'zombifying' proteins needed to keep the colonies' host cell alive. Wouldn't the number of mitochondria in the host cell (glial cell, smooth muscle, etc.) have a big impact on the number/productivity of the RBs and therefore on the effectiveness of the medications?

It seems like the metronidazolei or tinii might damage a certain number of CB's, maybe all the CB's, but that still wouldn't allow apoptosisi, because the CB's aren't keeping the host cell alive, it's the RB's that immortalize the cell by making proteins. In fact, if it weren't for the fact that the CB's can come back into production as RBs, there'd be no reason to kill them at all. 

It might help me understand if I use some fake numbers to illustrate:

Cell A is capable of supporting 100 RBs; it's maxed out; the minimum needed to immortalize the cell is 50. Host lysosomes kill some RBs, which need replaced on a continuous basis.

We start taking protein synthesis inhibitors; the minimum needed goes up to 70, because of inefficient synthesis; and 15 of the RBs go 'off-line' to conserve energy. The colony now has 15 more RBs than it needs. If the lysosomes kill 20 RBs, 5 CBs come back on-line, no big deal for the colony.

Now, if we take a bactericide, the minimum goes up to 80 because some of the RBs are busy repairing themselves. If the lysosomes get 20, and we've also killed 10 CBs, it's curtains; the cell dies and all the C.Pn. with it. Yay!

Cell B, though, is capable of supporting 500 RBs. Uh oh, this is going to take a while, because the minimums probably stay the same, and it has a lot more reserves.

Well, this post grew longer and longer. I'm mid-pulse right now, so I apologize in advance for any disjointedness. Please, if anyone can improve my fake numbers, jump right in: I just put them out there as yet another metaphor to try to understand this complex problem. 

Ron 

  

On Stratton protocol for CFSi starting 01/06 (NE Ohio, USA).

Ron

On CAPi for CFSi starting 01/06 (NE Ohio, USA)

Began rifampin trial 1/14/09

Currently: on intermittent

I wish I could just take tinidazole continuously until all my symptoms disppeared.

Thanks for the explanations of why we pulse and why it takes so long. 

minocycline, azithromycine, metronidazolei 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

Protein synthesis inhibitors must not be 100% effective, neither in forcing reticulate bodies into cryptic bodies, nor in stopping protein synthesis. If they were, the synthesis of HSPi<i<-60 would cease, the cell would die normally, and the C.Pn. inside it would die as well.

Hi Ron,

This is probably dose dependent with doses needed to be 100% effective being unrealistic (Not to mention dangerous.) Cpni is only vulnerable inside of cells. And getting a high concentration of drugs into cells is difficult as cells tend to expel substances of no value (they just do not understand that the ABXi are of value...) via eflux pumps. Additionally Cpn have their own set of pumps that expel drugs. A handful of drugs develop very high tissue concentration which overcomes at least one part of this problem. Two that come to mind are Zithromax and Hydroxychloroquine which both achieve higher tissue than serum concentrations. So presumably they are not pumped out by cells. They may still be (and probably are based very unscientifically upon side effects) pumped out by Cpn though.

BTW I am a little suprised that no one has ever tried slowly increasing the doses of the protein synthesis inhibitors. Or maybe they have tried this and did not survive to warn us against this ;) I am not suggesting anyone try this BTW but I would be very curious if anyone has ever significantly increased their doses of Zithro and/or Doxyi. I used to take 250 mg of Zithro daily and felt like that worked better than 3 x per week. And I don't mean so mamby pamby dose like once I lost track and took 600 mg of Doxy in 24 hours... Has anyone ever tried taking 1-2 grams of Doxy and/or 500 mg of Zithro over a sustained period. I am NOT suggesting people try this but it might be instructive to hear the results if someone has.

- Paul 

Ron, a question about the number of cpni that can infect a cell....For some reason, the image of one organism per cell was in my mind. What is the scale of the cpn organism in relation to the cell? And don't they siphon off the mitochondria of that cell? The images I have seen haven't matched with having such a quantity of organisms in one cell:

"Cell A is capable of supporting 100 RBs; it's maxed out; the minimum needed to immortalize the cell is 50. Host lysosomes kill some RBs, which need replaced on a continuous basis. "

Need more pictures to see this clearly. Are there any out there?

And Jim was saying something about re-starting the Cpn lab at Vanderbilt. Have they stopped doing work there on Cpn? This would be a sad thing. Do they need support?

Raven 

 

Feeling 98% well-going for 100. Very low test for Cpni. CAPi since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NACi,BHRT, MethyB12 FIRi Sauna. 1-18-11 begin new treatment plan with naturopath

Paul- Lab rat here. Due to a misunderstanding of the protocol I took 500mg Azithromycin daily in addition to 200mg doxyi for at least 4-5 months. As for results-- I certainly grew to tolerate the dose! Can't say that it was better since I have nothing to compare it to, but I've dropped back to 500mg MWF and can't say I'm worse for it. The only side effect I had on that dose was some tinnitus">i, which is common, but one does have to watch out for it becoming permanent. Has a not-so-nice ring to it.

Raven- Yes, they don't have an active Cpni lab. This takes $$$: $50,000 a year per lab assistant, and they had three of them when it was up and running. How to get this going again should be a priority for us soon!

On CAPi's protocol for Cpn in CFSi/FMSi since December 2004.
Currently: 150mg INHi, Doxy/Zith, Tinii pulses 

"I really didn't say everything I said." Yogi Berra

 

CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral

Paul, doxyi has some potentially touchy liver and kidney toxicity ceilings. I recall a lyme friend of KK2's reported some rather high doses. I didnt feel very successful in ascertaining whether I thought those were safe, based on what I could find in the lit. Add in other drugs simultaneously and the calculus gets hairier and less precise - drugs interact not only thru inducing/inhibiting CYP enzymes, but also thru competing for (human) efflux pumps, etc, which are involved in drugs' expulsion into urine, etc.

Liver toxicity due to tetracyclines appears to be somewhat more a problem for women than men... also the postpartum state brings the vulnerability to a new level because of odd effects it can have on the liver. I found lit on serious liver problems in postpartum women due to ordinary or near-ordinary doses of tetracyclines.

Ron & Paul,

Efflux is an interesting one. I used to work on that idea every day. But I found it hard to use efflux to explain the differences between our diseasesi and classical bacterial diseases. Why should bacteria be doing heavy efflux in MSi and CFSi, but not doing it in bladder infectionsi, tuberculosis, strep throat, or acute chlamydial afflictions?

Well, many of the efflux pumps are extrordinary nonspecific. The same pump might be able to extrude both abxi and antimicrobial peptides made by human cells. Something like this might provide a "motive" for the pumps to be upregulated strongly in certain infectious situations. And I found a paper (W Schafer) where antimicrobial peptides induced 10-fold extra expression of efflux pumps by neisseriae.

But I'm not sure 10-fold is really enough. We are talking about high-level abxi resistance here, much higher than 10-fold. Also, I looked at a complete differential transcriptome of chlamydiae in the IFNg-induced persistent state. This shows all the differences in the expression levels of various genesi in the IFNg persistencei state as compared to in normal happy chlamydiae. No efflux pump was upregulated much (at least, no known one), at least not at the transcription level. One limitation of this is that the cDNA chips used for these experiments are not really all that accurate or sensitive.

Heck, I cant find evidence of anything at the RNA or protein levels that looks way, way different in persistent chlamydiae, whether its intramacrophage persistence or IFNg-induced persistence. There are some genes whose expression changes a couple-fold. But persistence creates such amazing differences in abx sensitivity that I feel like there should be some genes being regulated 50-fold, not 2-fold. Schoolnik found many genes that were 800-fold induced in dormant Mycobacterium tuberculosis compared to growing ones; now thats what I call a change! I've looked for something like that in many other bacterial stress states but havent found it.

So anyway, I kind of lost enthusiasm for the efflux-centered model. But I'm still 80% sure that something fundemental is going on in common in all these diseases, that no one has figured out. I fancied heat shock proteins for a while. Like efflux pumps they interact with tons of different molecules - this gives the explanatory power for why sensitivity to abx with a variety of totally unrelated targets can be affected. But the idea doesnt add up at all. If heat shock proteins were to block all the different abx binding sites, theres probably no way the bacterium could maintain viability.

Every day I try to solve the puzzle. One day someone probably will. The power of science is inconceivable. There was not even any molecular biology at all until the 1950s, when all of a sudden all the basics got figured out pretty rapidly - half of it by Linus Pauling and the other half by everyone else. And nowadays many of the understandings of the 1980s look primative.

Eric, I am glad to know you are doggedly trying to solve this puzzle.  I have found your postings to be quite helpful.  You might someday go down in the history books along with Stratton and Wheldon. 

"What saves a man is to take a step.  Then another step"

-C.S. Lewis

Wheldon Protocol for rrmsi since Oct '05.  Added LDN 4.5mg qhs Oct '07.  All supp's.  Positive IGGi's for Lyme Disease,Babesia, & Erlichiosis Sept. 2008.  Currently:  Mepron 750mg bid and Azithromycin 250mg qdi for Babesia.

Raven, I think the best images are in The Potbelly Syndrome: check out the thread at http://www.cpnhelp.org/?q=revelation_to_me_maybe_ob<. There's also a link there in Jim K's post to an online diagram that kind of approximates what I see in the book's photo.

Ron

On Stratton protocol for CFSi starting 01/06 (NE Ohio, USA).

Ron

On CAPi for CFSi starting 01/06 (NE Ohio, USA)

Began rifampin trial 1/14/09

Currently: on intermittent

Ron heres some old stuff on "miraculous" translation despite anti-ribosomei drugs. Lotta mystery here and little clarity, alas.

http://www.pubmedcentral.gov/picrender.fcgi?artid=217288&blobtype=pdf<

http://www.pubmedcentral.gov/picrender.fcgi?artid=93581&blobtype=pdf<

http://tinyurl.com/klsmv<

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