Fluoroquinolone

[BBC3]

NOw thats some seious reaction. I still cant help but think as all things that the quinolones will all still act somewhat differently... The first one I ever took was Avelox ( third gen I think). Tendons were all I noticed, NOTICED. My two year old daughter had cipro with no apparent issues... Who knows, perhaps I am CRAZIER than I was before. But that would be hard to do...[)]

Stay away. Seriously lethal. I developed side effects i never believed i would. Its the second drug after finasteride that harmed me so bad. Offcourse before fin it didn't affect me much, but after i was wacked by the dreadful sides from finasteride ciprofloxacin just added another nightmare. It messes up thyroid VERY BAD. I couldn't sweat for months post this shit, and developed some weird form of depersonalisation, went to the docs they told me my TSH is gone wild. It only took 17 of them pills to do that.

Offcourse had all the weird sides like tendon pains and joint aches. Its so strong, a pharmacist friend took it and had 4 weeks back ache he couldn't move, my father's secretary lost her hearing for like 6 months and still she has tinnitus and dizziness.

Ahh dizziness is also something i had too, and headaches and the biggest pain in the ass is if you dare combine it with cortisol or anti-inflammatories i heard of people developing mental sides and pressure in their head from just a few pills of cipro.

Also another friend of mine had to stay 3 months of the swimming pool after 10 pills of cipro because of fatigue and dizziness. He also stated he couldn't sweat even when his temperature rose to 40 degrees celcius.

Sickening drugs

 

[CubbieBlue]

Stay away. Seriously lethal. I developed side effects i never believed i would. Its the second drug after finasteride that harmed me so bad. Offcourse before fin it didn't affect me much, but after i was wacked by the dreadful sides from finasteride ciprofloxacin just added another nightmare. It messes up thyroid VERY BAD. I couldn't sweat for months post this shit, and developed some weird form of depersonalisation, went to the docs they told me my TSH is gone wild. It only took 17 of them pills to do that.

Offcourse had all the weird sides like tendon pains and joint aches. Its so strong, a pharmacist friend took it and had 4 weeks back ache he couldn't move, my father's secretary lost her hearing for like 6 months and still she has tinnitus and dizziness.

Ahh dizziness is also something i had too, and headaches and the biggest pain in the ass is if you dare combine it with cortisol or anti-inflammatories i heard of people developing mental sides and pressure in their head from just a few pills of cipro.

Also another friend of mine had to stay 3 months of the swimming pool after 10 pills of cipro because of fatigue and dizziness. He also stated he couldn't sweat even when his temperature rose to 40 degrees celcius.

Sickening drugs

HOw long did it take your tendon/joint/muscle pain to subside, if it ever did?

 

[OhNoYo]

Well, last nite I attempted to walk on the treadmill to try and get back into my normal training routine. Both achilles startd hurtn a few minutes into it, so I decided to quit about 10min into incline training outa fear I may tear them. So, I guess walking on an incline like I used to do for my traditional routine is out the windo! Though, I did still walk on the treadmill, just lowered the incline to zero and sped up the pace, which gets my HR to right around I want it to be, so at least that's a plus...

However, today I noticed that the LOWER SIDE of my right calf hurt like hell. The front kinda hurt, too. I didn't know what it could be, til I looked it up on the internet, and it might be peroneal muscles and/or peroneal tendon. I think the damn Cipro caused it to happen from last night walking on an incline like that since I took it!

I still walked on the treadmill tonight though like I normally do, even though the lower side of my calf hurt the whole fucking time! I'm tired of this affecting my life, so I decided to just push thru it, hopefully only pain will be the outcome, and not an injury! [}]

 

[CubbieBlue]

Well, last nite I attempted to walk on the treadmill to try and get back into my normal training routine. Both achilles startd hurtn a few minutes into it, so I decided to quit about 10min into incline training outa fear I may tear them. So, I guess walking on an incline like I used to do for my traditional routine is out the windo! Though, I did still walk on the treadmill, just lowered the incline to zero and sped up the pace, which gets my HR to right around I want it to be, so at least that's a plus...

However, today I noticed that the LOWER SIDE of my right calf hurt like hell. The front kinda hurt, too. I didn't know what it could be, til I looked it up on the internet, and it might be peroneal muscles and/or peroneal tendon. I think the damn Cipro caused it to happen from last night walking on an incline like that since I took it!

I still walked on the treadmill tonight though like I normally do, even though the lower side of my calf hurt the whole fucking time! I'm tired of this affecting my life, so I decided to just push thru it, hopefully only pain will be the outcome, and not an injury! [}]

Sorry to hear that man. I would take some time off and retest it in a few weeks.

 

[CubbieBlue]

Just to reiterate, tendinosis should take around 150 days to heal. A tendon rupture? A year plus.

So...take it easy!

 

[CubbieBlue]

Had a re-check at my physical therapist today. Range of motion increased in all effected joints. Some by as much as 12 degrees. My pain/disability index test I scored 50% better on than when I began. He basically told me to continue doing exercises on my own as ultrasound will do no more good. Will re-check in 3 weeks and see where I am at.

I was able to shovel yesterday for 2.5 hours and didn't pull/pop/tear anything.

Major issues still are:
Plantar fasciitis/achilles pain
Hand pain after using a computer all day
Knee pain on awkward movements
lower Back pain has improved with stretches, but can still be bothersome

New protocol is:
Everyday - 20 minutes stretching AM, all effected body parts.
M/W/F - back to lifting program (stronglifts 5x5, but starting with eccentric squats with just the bar) 30 minutes bike

T/Th - eccentric knee, heel exercises - rest basically
Sat - rest
Sun - Swim

If all goes great, hopefully I can begin running the week of the 28th....which would put me at about 60 days post severe reaction, and 90 days since I last ingested a quinolone.

Sleep is improving but eyelid still twitching.

 

[OhNoYo]

Had a re-check at my physical therapist today. Range of motion increased in all effected joints. Some by as much as 12 degrees. My pain/disability index test I scored 50% better on than when I began. He basically told me to continue doing exercises on my own as ultrasound will do no more good. Will re-check in 3 weeks and see where I am at.

I was able to shovel yesterday for 2.5 hours and didn't pull/pop/tear anything.

Major issues still are:
Plantar fasciitis/achilles pain
Hand pain after using a computer all day
Knee pain on awkward movements
lower Back pain has improved with stretches, but can still be bothersome

New protocol is:
Everyday - 20 minutes stretching AM, all effected body parts.
M/W/F - back to lifting program (stronglifts 5x5, but starting with eccentric squats with just the bar) 30 minutes bike

T/Th - eccentric knee, heel exercises - rest basically
Sat - rest
Sun - Swim

If all goes great, hopefully I can begin running the week of the 28th....which would put me at about 60 days post severe reaction, and 90 days since I last ingested a quinolone.

Sleep is improving but eyelid still twitching.

Sounds as if you're already past the top of the shitty, depressed mountain and now working ur way back down it to normalcy!

 

[CubbieBlue]

Sounds as if you're already past the top of the shitty, depressed mountain and now working ur way back down it to normalcy!

One day I am, one day I am not. It is very weird. One day I can feel almost normal and the next I feel like I want to put a bullet in my brain. At this point I still have not gone an hour without some weird ache or pain somewhere. I will not be happy until I can run again. When that will be...who knows. Hopefully within the next 30 days.

Quite frankly I am happy it is not getting worse. And I hope it doesn't. Stuff like this really makes you wonder if God is punishing you for bad decisions you have made previously in life or something..

 

[CubbieBlue]

One day I am, one day I am not. It is very weird. One day I can feel almost normal and the next I feel like I want to put a bullet in my brain. At this point I still have not gone an hour without some weird ache or pain somewhere. I will not be happy until I can run again. When that will be...who knows. Hopefully within the next 30 days.

Quite frankly I am happy it is not getting worse. And I hope it doesn't. Stuff like this really makes you wonder if God is punishing you for bad decisions you have made previously in life or something..

I think the worst part is that even though piece by piece every body part has improved, when I try to put all of the pieces together to say, do a deadlift, it is like taking a bunch of engine parts that almost work good, but don't quite, and trying to start the engine. It will turn over and will run for a little bit, but it will look, sound, and feel like shit. The other day I was very confused at how bad I thought I felt yet at how my charting of progress kept going up and up and up. I just wasn't looking at the picture as a whole. Now, I am.

The bad thing is that I am running out of different stuff to try. There is a doctor that does prolotherapy nearby and he actually has pretty good prices but I am not sure if I want to give it a shot just yet. Anyone have any experiences?

 

[OhNoYo]

One day I am, one day I am not. It is very weird. One day I can feel almost normal and the next I feel like I want to put a bullet in my brain. At this point I still have not gone an hour without some weird ache or pain somewhere. I will not be happy until I can run again. When that will be...who knows. Hopefully within the next 30 days.

Quite frankly I am happy it is not getting worse. And I hope it doesn't. Stuff like this really makes you wonder if God is punishing you for bad decisions you have made previously in life or something..

I think the worst part is that even though piece by piece every body part has improved, when I try to put all of the pieces together to say, do a deadlift, it is like taking a bunch of engine parts that almost work good, but don't quite, and trying to start the engine. It will turn over and will run for a little bit, but it will look, sound, and feel like shit. The other day I was very confused at how bad I thought I felt yet at how my charting of progress kept going up and up and up. I just wasn't looking at the picture as a whole. Now, I am.

The bad thing is that I am running out of different stuff to try. There is a doctor that does prolotherapy nearby and he actually has pretty good prices but I am not sure if I want to give it a shot just yet. Anyone have any experiences?

As in run, I believe you are speaking of jogging and not sprints, correct? Do you think your Achilles Tendons are gonna rupture if you try to jog, Sir?

Speaking of which, I did do some jogging about a week ago and unfortunately unlike the first time it hurt both achilles and I stopped like I usually do after 10min of jogging on the treadmill at a 6mph pace to complete a mile, but instead of staying on the treadmill to walk it, I stopped annoyed, frustrated, and nervous at possibly hurting myself. I actually wanted to have a productive workout in the gym that day after the treadmill but just went home extremely angry and dissappointed.

As for just walking on the treadmill for an hour/day @ 4mph, I've been doing that and although it hurts my achilles and knees at times, I just decided to say fuck it and push thru, cuz I'm tired of this bulsht affecting my life. Actually, the more I think about it, the less it hurts and bothers me.

I did want to ask you about the Achilles Tendon "twinges" you state you have though because I guess I had one of those cuz the back of my Achilles Tendon today got a real sharp, shooting pain that hurt like hell. It made me scared for a bit cuz I thought it might have partially ruptured, though I was walking normal and still got on the treadmill for my normal routine today with the normal pain as usual, but nothing more. I take it what I had are the types of twinges you are speaking of? I really don't think I could have torn anything, excluding microtears which happen to even normal ppl daily.

 

[CubbieBlue]

As in run, I believe you are speaking of jogging and not sprints, correct? Do you think your Achilles Tendons are gonna rupture if you try to jog, Sir?

Speaking of which, I did do some jogging about a week ago and unfortunately unlike the first time it hurt both achilles and I stopped like I usually do after 10min of jogging on the treadmill at a 6mph pace to complete a mile, but instead of staying on the treadmill to walk it, I stopped annoyed, frustrated, and nervous at possibly hurting myself. I actually wanted to have a productive workout in the gym that day after the treadmill but just went home extremely angry and dissappointed.

As for just walking on the treadmill for an hour/day @ 4mph, I've been doing that and although it hurts my achilles and knees at times, I just decided to say fuck it and push thru, cuz I'm tired of this bulsht affecting my life. Actually, the more I think about it, the less it hurts and bothers me.

I did want to ask you about the Achilles Tendon "twinges" you state you have though because I guess I had one of those cuz the back of my Achilles Tendon today got a real sharp, shooting pain that hurt like hell. It made me scared for a bit cuz I thought it might have partially ruptured, though I was walking normal and still got on the treadmill for my normal routine today with the normal pain as usual, but nothing more. I take it what I had are the types of twinges you are speaking of? I really don't think I could have torn anything, excluding microtears which happen to even normal ppl daily.

By run I mean sprint, jump, jog, do anything I want.

I don't know if they will rupture, but I think the damage done sustained will continue to be damage that my body cannot heal from overnight. I think my best bet is to keep the damage minimal and the blood flow high to stimulate recovery. Most of the stuff I have recently been reading states that chemically induced tendinosis does not heal in a linear pattern like regular tendinitis does. It kind of peters along and then spontaneously resolves rapidly. The think that perhaps I am doing damage to myself by pushing myself. I am pushing myself because I do not want to get out of shape and weak...but I will be of less use if I cannot move. So I guess I should stop pushing myself.

Yes - a sharp shooting pain would be like the twinges I experience. You didn't tear anything, but it sounds like you definitely have some form of tendinosis going on, which it sounds like has spread to your patellar tendons as well. It took about a month and a half for it to peak (I hope it's peaked) in me. Hopefully yours is peaking now, or has peaked.

What's worse is this shit also fucks up your collagen, which is in and around your joints. So I wonder how much the snapping/popping/grinding is actual joint and not tendon issues.

It's all fucking bullshit. Someone needs to do something about this shit. The FQ people try and try but no one listens to them.

 

[OhNoYo]

By run I mean sprint, jump, jog, do anything I want.

I don't know if they will rupture, but I think the damage done sustained will continue to be damage that my body cannot heal from overnight. I think my best bet is to keep the damage minimal and the blood flow high to stimulate recovery. Most of the stuff I have recently been reading states that chemically induced tendinosis does not heal in a linear pattern like regular tendinitis does. It kind of peters along and then spontaneously resolves rapidly. The think that perhaps I am doing damage to myself by pushing myself. I am pushing myself because I do not want to get out of shape and weak...but I will be of less use if I cannot move. So I guess I should stop pushing myself.

Yes - a sharp shooting pain would be like the twinges I experience. You didn't tear anything, but it sounds like you definitely have some form of tendinosis going on, which it sounds like has spread to your patellar tendons as well. It took about a month and a half for it to peak (I hope it's peaked) in me. Hopefully yours is peaking now, or has peaked.

What's worse is this shit also fucks up your collagen, which is in and around your joints. So I wonder how much the snapping/popping/grinding is actual joint and not tendon issues.

It's all fucking bullshit. Someone needs to do something about this shit. The FQ people try and try but no one listens to them.

Yes, I must admit precautions should be done. First, they REALLY need to start taking into mind the significant risks of other factors that have been known to amplify FQ tendon issues, such as renal impairment, old age, consequent corticosteroid use, etc. Also, physicians should stop prescribing this like its the next sliced bread and instead put into perspective how bad possible tendon rupture may be for their patient then weigh out benefits vs that particular risk. Don't get me wrong, it does one helluva job at being an antibiotic, BUT if you don't have anything too serious, Idk y they just can't take a little more time to try and find the source of what the infection is, instead of being just going right to the broad spectrum stuff right off the bat.

 

[CubbieBlue]

Well, I seem to have emerged from a serious depression over the last few days. Taking the day off work yesterday seemed to help. The joint issues are not abating however. Weight bearing exercise seems to make it worse, so I have pretty much decided to just give it a rest. My elbows weren't affected too bad by this but on Wednesday I did 5x5 bench with 225 loaded on. While I could complete it it seriously felt like my triceps were going to rip out of my body. This weight would not normally be difficult for me.

I think light work, stretching, and the bike will have to do to keep bloodflow up. I think my only hopes for recovery are either a spontaneous remission of symptoms (which I hope for every night) or I figure out the mechanism and figure out a treatment (probably not going to happen). There is one very good rheumatologist in town and he is so hard to get into that I am waiting until April.

I think what I am going to start doing is looking at diseases that present with a similar pathology and see if I can figure out any solutions from them. I also want to determine if perhaps quinolones trigger some sort of auto-immune response which causes these effects to occur.

 

[CubbieBlue]

While a bit hard to navigate, this website has pretty much every research article on FQ's ever written:FQResearch.org

 

[Michael Scally MD]

While a bit hard to navigate, this website has pretty much every research article on FQ's ever written:FQResearch.org

Another excellent informative thread by CubbieBlue. And the credit goes to the EXCELLENT posters at Meso!!!

 

[CubbieBlue]

Damage Mechanism

These articles seems to explain the damage mechanism of these drugs:

Ofloxacin induces oxidative damage to joint chondrocytes of juvenile rabbits: Excessive production of reactive oxygen species, lipid peroxidation and DNA damage.

Li Q, Peng S, Sheng Z, Wang Y.

Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong Da Jie Street, Fengtai District, Beijing 100071, PR China.

Quinolones are widely used in infection therapy due to their good antimicrobial characteristics. However, there potential joint chondrotoxicity on immature animals has stood in the way of the therapeutic application of these agents, the exact mechanism of which is still unclear. This study was undertaken to investigate the role of oxidative damage in ofloxacin (one typical quinolones)-induced arthropathy. Chondrocytes from juvenile rabbit joints were incubated with ofloxacin at concentrations of 0, 5, 10, 20, 40 and 80mug/ml, respectively. The extent of oxidative damage was assessed by measuring the reactive oxygen species level, activities of antioxidant enzymes, and oxidative damage to some macromolecules. It was observed that ofloxacin induced a concentration-dependent increase in intracellular reactive oxygen species production, which may be an early mediator of ofloxacin cytotoxicity. Similarly, ofloxacin resulted in a significant lipid peroxidation, revealed by a concentration-dependent increase in the level of thiobarbituric acid reactive substances. At the same time, ofloxacin induced DNA damage in a concentration-dependent manner for 24h measured by comet assay, which may be a cause for overproduction of reactive oxygen species. Furthermore, antioxidant enzyme activities, such as glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD), were rapidly decreased after treatment with ofloxacin. In addition, SOD decline and reactive oxygen species production were strongly inhibited, and the loss in cell viability was partly abated by additional glutathione (GSH), N-acetylcysteine (NAC) and dithiothreitol (DTT). In conclusion, these results clearly demonstrated that ofloxacin could induce oxidative stress, lipid peroxidation and DNA oxidative damage to chondrocytes.

PMID: 19818344 [PubMed - as supplied by publisher]

And another:

Neurotoxicology. 2006 Jan;27(1):6-10. Epub 2005 Aug 24. Links

Ciprofloxacin-induced DNA damage in primary culture of rat astrocytes and protection by Vitamin E.Gurbay A, Gonthier B, Signorini-Allibe N, Barret L, Favier A, Hincal F.

Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 06100 Ankara, Turkey. Aylingurbay@hotmail.com

Fluoroquinolones are generally well-tolerated antibiotics in patients. Gastrointestinal, central nervous system, and dermatological adverse events were the most frequent unwanted effects during therapy with these drugs. However, the mechanism of these adverse effects has not yet been elucidated. The aim of this study was to investigate the possible DNA damage-inducing effect of a fluoroquinolone (FQ) antibiotic, ciprofloxacin (CPFX) on primary culture of rat astrocytes. For this purpose, the cultured cells were incubated with various concentrations of CPFX, and DNA damage was monitored by comet assay. Our results showed a concentration-dependent induction of DNA damage by CPFX. Pretreatment of cells with Vitamin E for 4h provided partial protection against this effect. The data obtained in this study suggest that CPFX-induced DNA damage might be related to oxidative stress and should be considered for further mechanistic studies of central nervous system toxicity of CPFX.

So we have oxidative stress, lipid peroxidation, and DNA oxidative damage to chondrocytes. Chondrocytes are the types of cells found in cartilage. What is interesting is that the antioxidants Vitamin E, Glutathione and NAC served to partially abate this damage. DTT is described here although I do not understand it quite yet: [ame="http://en.wikipedia.org/wiki/Dithiothreitol"]Dithiothreitol - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/Fileithiothreitol.png" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/thumb/2/2e/Dithiothreitol.png/200px-Dithiothreitol.png"@@AMEPARAM@@commons/thumb/2/2e/Dithiothreitol.png/200px-Dithiothreitol.png[/ame]



This study discusses the disruption of collagen synthesis:

Ciprofloxacin-induced tendinopathy and tendon rupture have been previously described, principally affecting the Achilles tendon. This study was designed to investigate the effect of ciprofloxacin on expressions of matrix metalloproteinases (MMP)-2 and -9, tissue inhibitors of metalloproteinase (TIMP)-1 and -2 as well as type I collagen in tendon cells. Tendon cells intrinsic to rat Achilles tendon were treated with ciprofloxacin and then underwent MTT (tetrazolium) assay. Real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis were used, respectively, to evaluate the gene and protein expressions of type I collagen, and MMP-2. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and -9. Reverse zymography was used to evaluate TIMP-1 and -2. Immunohistochemical staining for MMP-2 in ciprofloxacin-treated tendon explants was performed. Collagen degradation was evaluated by incubation of conditioned medium with collagen. The results revealed that ciprofloxacin up-regulated the expression of MMP-2 in tendon cells at the mRNA and protein levels. Immunohistochemistry also confirmed the increased expressions of MMP-2 in ciprofloxacin-treated tendon explants. The enzymatic activity of MMP-2 was up-regulated whereas that of MMP-9, TIMP-1 or TIMP-2 was unchanged. The amount of secreted type I collagen in the conditioned medium decreased and type I collagen was degraded after ciprofloxacin treatment. In conclusion, ciprofloxacin up-regulates the expressions of MMP-2 in tendon cells and thus degraded type I collagen. These findings suggest a possible mechanism of ciprofloxacin-associated tendinopathy. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:67–73, 2011

 

[CubbieBlue]

From wiki:
[ame="http://en.wikipedia.org/wiki/DNA_repair"]DNA repair - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Brokechromo.jpg" class="image"><img alt="" src="http://upload.wikimedia.org/wikipedia/commons/b/b2/Brokechromo.jpg"@@AMEPARAM@@commons/b/b2/Brokechromo.jpg[/ame]
and
[ame="http://en.wikipedia.org/wiki/DNA_oxidation"]DNA oxidation - Wikipedia, the free encyclopedia@@AMEPARAM@@/wiki/File:Question_book-new.svg" class="image"><img alt="Question book-new.svg" src="http://upload.wikimedia.org/wikipedia/en/thumb/9/99/Question_book-new.svg/50px-Question_book-new.svg.png"@@AMEPARAM@@en/thumb/9/99/Question_book-new.svg/50px-Question_book-new.svg.png[/ame]

Sources of damage

DNA damage can be subdivided into two main types:

1. endogenous damage such as attack by reactive oxygen species produced from normal metabolic byproducts (spontaneous mutation), especially the process of oxidative deamination
1. also includes replication errors
2. exogenous damage caused by external agents such as
1. ultraviolet [UV 200-300nm] radiation from the sun
2. other radiation frequencies, including x-rays and gamma rays
3. hydrolysis or thermal disruption
4. certain plant toxins
5. human-made mutagenic chemicals, especially aromatic compounds that act as DNA intercalating agents
6. cancer chemotherapy and radiotherapy [FQs are chemotherapeutic drugs]
7. viruses [5]

The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation, for example, through gene conversion).
[edit] Types of damage

There are five main types of damage to DNA due to endogenous cellular processes:

1. oxidation of bases [e.g. 8-oxo-7,8-dihydroguanine (8-oxoG)] and generation of DNA strand interruptions from reactive oxygen species,
2. alkylation of bases (usually methylation), such as formation of 7-methylguanine, 1-methyladenine, 6-O-Methylguanine
3. hydrolysis of bases, such as deamination, depurination, and depyrimidination.
4. "bulky adduct formation" (i.e., benzo[a]pyrene diol epoxide-dG adduct)
5. mismatch of bases, due to errors in DNA replication, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted.

Cells exposed to ionizing radiation, ultraviolet light or chemicals are prone to acquire multiple sites of bulky DNA lesions and double-strand breaks. [See Double Strand Breaks - next] Moreover, DNA damaging agents can damage other biomolecules such as proteins, carbohydrates, lipids, and RNA. The accumulation of damage, to be specific, double-strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to DNA damage.[30] The global response to damage is an act directed toward the cells' own preservation and triggers multiple pathways of macromolecular repair, lesion bypass, tolerance, or apoptosis. The common features of global response are induction of multiple genes, cell cycle arrest, and inhibition of cell division.

Double-strand breaks

Double-strand breaks, in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to genome rearrangements. Three mechanisms exist to repair double-strand breaks (DSBs): non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination.[17] PVN Acharya noted that double-strand breaks and a "cross-linkage joining both strands at the same point is irreparable because neither strand can then serve as a template for repair. The cell will die in the next mitosis or in some rare instances, mutate."[2][3]
DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide ester bond between the phosphate backbone and the deoxyribose nucleotides.

In NHEJ, DNA Ligase IV, a specialized DNA ligase that forms a complex with the cofactor XRCC4, directly joins the two ends.[19] To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate.[20][21][22][23] NHEJ can also introduce mutations during repair. Loss of damaged nucleotides at the break site can lead to deletions, and joining of nonmatching termini forms translocations. NHEJ is especially important before the cell has replicated its DNA, since there is no template available for repair by homologous recombination. There are "backup" NHEJ pathways in higher eukaryotes.[24] Besides its role as a genome caretaker, NHEJ is required for joining hairpin-capped double-strand breaks induced during V(D)J recombination, the process that generates diversity in B-cell and T-cell receptors in the vertebrate immune system.[25]

Homologous recombination requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break. The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for chromosomal crossover during meiosis. This pathway allows a damaged chromosome to be repaired using a sister chromatid (available in G2 after DNA replication) or a homologous chromosome as a template. DSBs caused by the replication machinery attempting to synthesize across a single-strand break or unrepaired lesion cause collapse of the replication fork and are typically repaired by recombination.

Topoisomerases introduce both single- and double-strand breaks in the course of changing the DNA's state of supercoiling, which is especially common in regions near an open replication fork. Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them.

 

[chemman]

Holy s*** that website is scary.

I didn't realize the psychiatric disturbances those drugs can cause. Antibiotic-induced psychosis?

I had a similar reaction to arimidex. Extreme anxiety, ocd, and paranoia, depression, etc. insomnia, welts on my leg, and even the tendon problems.

Drug side effects are very real.

 

[CubbieBlue]

Herbal OTC DNA Damage Repair

In vivo supplementation with coenzyme Q10
enhances the recovery of human lymphocytes
from oxidative DNA damage

http://www.fasebj.org/content/15/8/1425.full.pdf

Currently taking.

DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study.
Phytomedicine. 2001 Jul;8(4):275-82.
The Uncaria tomentosa water extracts (cat's claw, C-Med-100) have been shown to enhance DNA repair, mitogenic response and leukocyte recovery after chemotherapy-induced DNA damage in vivo. In this study, the effect of cat's claw C-Med-100 supplement was evaluated in a human volunteer study. Twelve apparently healthy adults working in the same environment were randomly assigned into 3 groups with age and gender matched. One group was daily supplemented with a 250 mg tablet containing an aqueous extract of cat's claw, and another group with a 350 mg tablet, for 8 consecutive weeks. DNA repair after induction of DNA damage by a standard dose of hydrogen peroxide was measured 3 times before supplement and 3 times after the supplement for the last 3 weeks of the 8 week-supplement period. There were no drug-related toxic responses to cat's claw supplement when judged in terms of clinical symptoms, serum clinical chemistry, whole blood analysis and leukocyte differential counts. There was a statistically significant decrease of DNA damage and a concomitant increase of DNA repair in the supplement groups (250 and 350 mg/day) when compared with non-supplemented controls. There was also an increased tendency of PHA induced lymphocyte proliferation in the treatment groups. Taken together, this trial has confirmed the earlier results obtained in the rat model when estimating DNA repair enhancement by cat's claw.

Currently taking.

 

[CubbieBlue]

Attached is a report completed by a FQ sufferer that is full of anecdotal (but useful) information regarding FQ Toxicity, what makes it better, what makes it worse, etc. It attempts to serve as somewhat of a case study as it follows progress of 42 effected individuals.