There is a misunderstanding here, I think. This is definitely not, what I was saying.
Here is a more complete quotation of my words in the quercetin thread: As to mtDNA, I believe, that it has never really been proved to this date, that the quinolones are directly damaging mtDNA. Stahlmann et alii did also show that they attack the mitochondria and that these as a reaction did enlarge, but there is no exact detailed knowledge about the mechanism which take place inside the mitochondria after the attack and/or specific damage.
Maybe you have seen research articles about this, I didn't.
Remember, that the mitichondria exist of 5 very ingenious complexes. Every disturbance in one of these "factory departments" will ultimately result in disturbing/decreasing the energy supply in the body cells involved. However, already long before this poison reaches the mitochondria membranes, it causes all kinds of damage before and after entering the cell matrix. So there are various moments, when metabolism is disturbed. All these moments cause decrease of energy production.
So, I certainly didn't say, that the (fluoro)quinolones don't cause mitochondrial dysfunction. I was clear enough, I believe.
I am sure they do cause all kinds of serious damage, ultimately resulting in decrease of energy production, there is enough scientific evidence about that. But there has to be made a clear distinction between indirect (mediated) influence and direct mtDNA killing, in my opinion. Concerning very direct damage caused by the fluoroquinolones inside of the membranes of the mitochondria, where the energy complexes are also located and/or to the mtDNA there isn't much detailed, exact information available though.
What we all need is real strong evidence, isn't it? This is all to much about suggesting, postulating, hypotheses, theories, just like this: (With all respect fqhelp):
"These results suggest that ciprofloxacin may be causing cytotoxicity by interfering with a mitochondrial topoisomerase II-like activity, resulting in a loss of mtDNA. "
I was preparing a longer post about this, but wanted to let you know this for now, since I did read these two former reactions now. (It is matter of a lack of time and I want to take this subject very serious).
And to clarify: I wrote: Just to clarify, that in your opinion, there is NO evidence to support that Quinolones (or other meds for that matter) cause damage to mtDNA?
Your reply:
Quote:
So, I certainly didn't say, that the (fluoro)quinolones don't cause mitochondrial dysfunction. I was clear enough, I believe.
NB. I didn't write mtDNA dysfunction... There is quite a difference!! I wrote: "Just to clarify, that in your opinion, there is NO evidence to support that Quinolones (or other meds for that matter) cause damage to mtDNA?"
As we all know, MtDNA dysfunction is different to "damage to mtDNA."
Quote:
What we all need is real strong evidence, isn't it? This is all to much about suggesting, postulating, hypotheses, theories, just like this: (With all respect fqhelp):
Research papers are about hypotheses, and postulating.
There is no such thing as "proven" written in research in papers, it is always hypothesis, and various methods of statistical analysis to either support or null the hypo. It cannot be "proven. Please see what hypothesis means, and why this is very important to make a distinction.
"A hypothesis (from Greek ὑπόθεσις [iˈpoθesis]) consists either of a suggested explanation for an observable phenomenon or of a reasoned proposal predicting a possible causal correlation among multiple phenomena.
ven though the words "hypothesis" and "theory" are often used synonymously in common and informal usage, a scientific hypothesis is not the same as a scientific theory. A Hypothesis is never to be stated as a question, but always as a statement with an explanation following it. It is not to be a question because it states what he/she thinks or believes will occur."
In regards to mitochondria, it is mostly hypothesis and postulation posted in this thread, and there is strong evidence already about meds causing damage to mtDNA.
Politics is involved here, and I doubt very much that the manufacturers of FQs are going to allow scientists "prove" that FQs causes damage to mitochondria any time soon. It will happen, but not now.
We are not discussing established theories concerning mtDNA.
None of us have Ph.Ds in biocellular science, and this is far above our intellect and knowledge. Some of us are very seriously ill, good hypotheses is all we have, helping many of us preventing further damage to ourselves.
I have nothing more to add to this "misUnderstanding" except to thank FQ and those who have kindly participated with their input in a civil, gentle, non-aggressive and respectful manner, whilst keeping discussion fair, and honest, impersonal and to the subject matter.
Pharmedt2: What did exactly does this mean? Your reply would stimulate further debate, research, and perhaps bring forward pieces of this puzzle.
Could you elucidate further about quinolones are not directly damaging mtDNA, are you suggesting, they are not impairing, or causing mito dysfunction, or not cytotoxic, or for eg. causing mito damage through a mito gyrase?
Thnks
I did write, that I was preparing a reply to this question of yours before I saw the later reactions. These interfered with what I originally wanted to answer.
QUOTE: Politics is involved here, and I doubt very much that the manufacturers of FQs are going to allow scientists "prove" that FQs causes damage to mitochondria any time soon. It will happen, but not now.
Notwithstanding that I have found a research article yesterday about direct damage to mtDNA by a quinolone. It is not easy to find research about direct damage by quinolones to non bacterial mtDNA. As the DNA in bacteria and mtDNA are alike, but not the same, this is important. So my reply would have contained this link already posted now by fqhelp http://www.ncbi.nlm.nih.gov/pubmed/10216214
Research articles are also about finding evidence, which is essential in science. Indeed scientists don't use the word "prove" or "proven", they say "show"or "shown" and demonstrate(d).
I myself do believe, that scientific evidence can and will make a difference.
Finally, in order to keep the discussion fair, honest, respectfull and to the subject I want to say, that it is also very important to quote a person's words in a correct way.
Joined: Apr 2007 Gender: Male Posts: 115 Karma: 10
Re: Drug toxicities and mitochondrial dysfunction « Reply #32 on Apr 6, 2009, 9:07pm »
Thank YOu. Sorry for not checking and reading all suggestions until now. been very depressed and trying not to use hands much and resting arms except some gentle physical therapy stretches. I have MRI's from 10 years ago that showed tendon ruptures in achilles (2) and then MRI's from about 2 years ago on legs... again... bad news. lots of damage... and now MRI of elbow showing tears, etc. very painful, depressing. so, it sounds like I would have a good case.! thank you for feedback. i'll keep you informed... will take time. paul
Joined: Apr 2007 Gender: Male Posts: 115 Karma: 10
Re: Drug toxicities and mitochondrial dysfunction « Reply #33 on Apr 6, 2009, 9:33pm »
About the Mom who was OK with a quin and daughter not... isn't it all a matter of how much and what dose was taken... and what was in the body prior to and during taking the fq? Was wondering if the Mom had a different 'strain' of fq and a different dose/ duration. thanks for all this info... what is needed now is research on MRI's or biopsy's of other body parts that are not initially affected... ie: my tendons had MRI's after the ruptures... 10 years ago... but I wish at the same time I had an MRI done of my elbows. It probably would have shown very minor damage at that point also... but not at the level of feeling it. after normal use for 10 years... now my elbows have reached point of tears and lots of pain.. and hands too. since so many people are injured... this research should be relatively 'easy" to find at a large hospital if doctors can be found to do it when a fq victim comes in with a tendon rupture in one area... check out the other areas too that do not have immediate pain. i repeat myself... brain effects??
Re: Drug toxicities and mitochondrial dysfunction « Reply #34 on Apr 7, 2009, 2:14am »
Thank you for all your input. It's great to have intelligent discussions like this.
Nobody knows what causes these serious, long term adverse reactions, quinolone induced mitochondrial dysfunction due to mtDNA alterations could very well be an answer to this confounding question. As I have posted earlier, direct mtDNA damage has already been shown, however, the significance of this is not fully understood.
Paul, I'm very sorry to hear about your experience. Regarding your questions about delayed effects and CNS reactions. Quinolones have extremely powerful penetrative abilities, and are able achieve high intracellular contentrations (so they definitely reach the mitochondria). Hidden ultrastructural damage is already shown to occur with quinolones. Mice given a single near-therapeutic dose of quinolones showed persisting ultrastructural damage (ultrastructural includes intracellular damage):
The finding that these rather low single dose of a fluoroquinolone induce ultrastructural changes in Achilles tendons from rats, which were not associated with clinical symptoms and which were still present 4 weeks after treatment, is of concern.
In cells incubated for several days with 25 mug/ml ciprofloxacin, a 60% reduction of mtDNA content... was observed... Data presented in this paper clearly demonstrate that ciprofloxacin at a concentration of 25 μg/ml causes a significant reduction in the mtDNA content in Jurkat cells.
Joined: Aug 2008 Gender: Male Posts: 130 Karma: 14
Re: Drug toxicities and mitochondrial dysfunction « Reply #35 on Apr 7, 2009, 3:27am »
If you read the flox report it states that there is widespread cell death. I have comunicated withe several floxed doctors and all the symptoms are said to athropathy and tendonopathy. The tendonitis and arthritis suggest inflamation. The main problem is the joints, tendons and maybe brain are starved of oxygen. Non inflammatory vasculitis ( no elevated markers).The joints are no longer functioning as before. The dried out withered tendons do not hold the joint together. This cause friction and inflamation. If i have a red hot bath I suffer no pain and its bliss. I hour post the bath the pain returns and low level throbbing and aching. The tendons in my major joints just flop about, so much so my hips dislocate when trying to do back exercises. Dna is damaged and the cells realise this and commit suicide. Shame the quinolone forum died , Dr Plum did a really good explaination of the mechanism. Hope not too much DNA dies off today:) Bob
If you read the flox report it states that there is widespread cell death. I have comunicated withe several floxed doctors and all the symptoms are said to athropathy and tendonopathy. The tendonitis and arthritis suggest inflamation. The main problem is the joints, tendons and maybe brain are starved of oxygen. Non inflammatory vasculitis ( no elevated markers).The joints are no longer functioning as before. The dried out withered tendons do not hold the joint together. This cause friction and inflamation. If i have a red hot bath I suffer no pain and its bliss. I hour post the bath the pain returns and low level throbbing and aching. The tendons in my major joints just flop about, so much so my hips dislocate when trying to do back exercises. Dna is damaged and the cells realise this and commit suicide. Shame the quinolone forum died , Dr Plum did a really good explaination of the mechanism. Hope not too much DNA dies off today:) Bob
Bob
LOL, Bob, well said. It is not just about the science for us floxies, or suffering from ADR from Quins cousins.
My body is biologically, the body of a 90 year old woman. A neighbor in her 80s walks faster than I do. Her cells are alive and beaming with energy and life... She is full of buzz and zinc I feel at times, that even breathing is robbing me of precious time.
For those interested, there is a table in this paper concerning nutrients, and the mention of Zinc, Vit B12 and so forth in the article. Apparently, these help with mito, but, even scientists themselves admit that knowledge is limited.
Mitochondrial Gene Expression: Influence of Nutrients and Hormones
Abstract
Mitochondrial gene transcription research has exploded over the last decade. Nuclear-encoded proteins, nutrients, and hormones all work to regulate the transcription of this genome. To date, very few of the transcription factors have been shown to have negative effects on mitochondrial gene expression, although there are likely conditions where such downregulation may occur.
Key Words: mitochondrial DNA • transcription • oxidative phosphorylation • ATP • vitamin A
About the Mom who was OK with a quin and daughter not... isn't it all a matter of how much and what dose was taken... and what was in the body prior to and during taking the fq? Was wondering if the Mom had a different 'strain' of fq and a different dose/ duration. thanks for all this info... what is needed now is research on MRI's or biopsy's of other body parts that are not initially affected... ie: my tendons had MRI's after the ruptures... 10 years ago... but I wish at the same time I had an MRI done of my elbows. It probably would have shown very minor damage at that point also... but not at the level of feeling it. after normal use for 10 years... now my elbows have reached point of tears and lots of pain.. and hands too. since so many people are injured... this research should be relatively 'easy" to find at a large hospital if doctors can be found to do it when a fq victim comes in with a tendon rupture in one area... check out the other areas too that do not have immediate pain. i repeat myself... brain effects??
Hi Paul, sorry about your pain. It would be nice to have a magic want and wish it all away...
Other than MRIs, were other tests performed, form spinal fluid etc...?
I was supposed to have the lumbar puncture and muscle biopsy, today, but again, postponed it. I feel to ill to have this done, and expect a major relapse post invest, just putting it off..
Some mtDNA tests were performed, but neuro, said abnomalities could not be interpreted. Likewise for others who had similar tests done.
Besides, apart from some hereditary mito diseases, we don't have the science for testing yet, and even the few tests that can be done at this point are unreliable.
Those of us, who undergo such sufferings fully understand what you are going, fully empathize with you, hang in there.
Re: Drug toxicities and mitochondrial dysfunction « Reply #38 on Apr 7, 2009, 10:20am »
"There is no such thing as "proven" written in research in papers, it is always hypothesis, and various methods of statistical analysis to either support or null the hypo. It cannot be "proven. Please see what hypothesis means, and why this is very important to make a distinction."
I just wanted to throw in one more molecule to this thread, that the concept of hypothesis is so overriding and is so foundational to research that we would have a difficult time finding people in the mainstream research universe capable of doing any work outside of that methodology. I've noticed lots of "research" done in Asia on Asian herbs, in which traditional Asian herbal treatments are tested under conventional Western research models (and with usually positive outcomes confiming benefits of those herbs: i.e., sanguisorba radix):
There is nothing wrong with coming up with intuitive models and hypothetical concepts. We should not hesitate doing this, in my opinion.
It is good to refer to external sources of evidence that supports a thought, but this is not always how great ideas evolve. Sometimes a great model or hypothesis is born from powerful intuition and with very little reference to historical evidence.
In my opinion!
With that in mind, I would throw another molecule out there and say that my intuition says that sometimes mitochondria are impacted in various ways, and that the cell that houses the mito may be damaged in yet another way. Do we know for sure in every cell situation, what happened to the cell and what happened to the cell's mito(s)? The situation is probably a feedback loop, and I would not assume that the mito is always the primary actor.
Regarding models, this seems to be a very visual way of thinking, that integrates a large variety of inputs. Why would we not want to illustrate this concept of the muscular reticulum except by illustration?
And I would agree with Beebs that there are many agents that antogonize mtDNA - that this is the nature of the modern chemically complex post-industrial world that we have created. I would bet that in the next 25 years, we will see a reversal of this, in which research discovers that so much disease was created by cumulative exposure to chemical toxins and medicines that the treatment for disease was largely a part of the problem - but by the time that occurs, so much DNA will have mutated that our kids will be just slightly different from us, in ways we cannot know.
Thank you for all your input. It's great to have intelligent discussions like this.
Nobody knows what causes these serious, long term adverse reactions, quinolone induced mitochondrial dysfunction due to mtDNA alterations could very well be an answer to this confounding question. As I have posted earlier, direct mtDNA damage has already been shown, however, the significance of this is not fully understood.
Paul, I'm very sorry to hear about your experience. Regarding your questions about delayed effects and CNS reactions. Quinolones have extremely powerful penetrative abilities, and are able achieve high intracellular contentrations (so they definitely reach the mitochondria). Hidden ultrastructural damage is already shown to occur with quinolones. Mice given a single near-therapeutic dose of quinolones showed persisting ultrastructural damage (ultrastructural includes intracellular damage):
The finding that these rather low single dose of a fluoroquinolone induce ultrastructural changes in Achilles tendons from rats, which were not associated with clinical symptoms and which were still present 4 weeks after treatment, is of concern.
In cells incubated for several days with 25 mug/ml ciprofloxacin, a 60% reduction of mtDNA content... was observed... Data presented in this paper clearly demonstrate that ciprofloxacin at a concentration of 25 μg/ml causes a significant reduction in the mtDNA content in Jurkat cells.
Thank you very much for your input here. This is the kind of articles I was looking for.
Now this research article about the inhibitory effects of fluoroquinolones on the transport of L-Carnitine shows one of the mediatory ways these drugs are causing decrease of mitochondrial function.
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Some of us are very seriously ill, good hypotheses is all we have, helping many of us preventing further damage to ourselves.
in a civil, gentle, non-aggressive and respectful manner, ![[image]](http://i144.photobucket.com/albums/r184/Floxed/Smilies/Thanks.gif)
whilst keeping discussion fair, and honest, impersonal and to the subject matter. 
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Her cells are alive and beaming with energy and life... She is full of buzz and zinc 
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