Flouroquinoline damage and Magnesium complexing

[Guest guest]

Looks llike the damage is from complexing magnesium -

And if I read this correctly - this is in vitro- and who knows if Mg

supplemtation would help in vivo..

A friends horse is about to receive a large dose of Baytrill for an

e.coli abscess (of pretty long duration) and we're worried about

flororquinoline tendon damage- now wondering if Mg supplemtation

will help...

But I guess this is just as applicable to humans- so why don't the

LLMDs that use these abx- know any of this????

Barb

: Vet Pathol. 2001 Mar;38(2):143-8. Links

In vitro evidence for effects of magnesium supplementation on

quinolone-treated horse and dog chondrocytes.Egerbacher M,

Wolfesberger B, Gabler C.

Institute of Histology and Embryology, University of Veterinary

Medicine, Vienna, Austria.

Quinolones and magnesium deficiency cause similar lesions in joint

cartilage of young animals. Chondrocytes cultivated in the presence

of quinolones and in Mg-free medium show severe alterations in

cytoskeleton and decreased ability to adhere to the culture dish. We

investigated whether Mg2+ supplementation can prevent quinolone-

mediated effects on chondrocytes in vitro. Chondrocytes cultivated in

Dulbecco's modified Eagle's medium/HAM's F-12 medium were treated

with ciprofloxacin (80 and 160 microg/ml) and enrofloxacin (100 and

150 microg/ml). Mg2+ was added at a concentration of 0.0612 mg/ml

(MgCl) and 0.0488 mg/ml (MgSO4) or a triple dose. In addition, cells

were cultivated in Mg-free medium and accordingly treated with Mg2+

supplementation. After 5 days in culture, the number of adherent

cells per milliliter was determined. The number of chondrocytes in

quinolone-treated groups decreased to 12-36% that of the control

group within the culture period. With Mg2+ supplementation, the

number of attached cells increased to 40-70% that of control cells.

The threefold dose of Mg2+ led to better results than did the single

dose. Cell proliferation tested by immunohistochemical staining with

Ki67 (clone MIB5) decreased from 70% in control groups to 55%, 48%,

and 30% in enrofloxacin-treated groups in a concentration dependent

manner (50, 100, and 150 microg/ml). Addition of Mg2+ did not

increase the rate of cell proliferation.

These results suggest that a great part of quinolone-induced damage

is due to magnesium complex formation, as Mg2+ supplementation is

able to reduce the effects in vitro. However, quinolone effects on

cell proliferation seem to be an independent process that is not

influenced by magnesium supplementation

[Guest guest]

Hi, Barb.

Thanks for posting this abstract. I have suspected that the

fluoroquinolones cause problems with the tendon attachment to bone

because the flouride binds magnesium at the junction, interfering

with the adhesion of the tendon. Magnesium fluoride is very

insoluble, meaning a strong bond forms between magnesium and

fluoride. I think this is why a seemed to get some relief when

she supplemented magnesium, since this would provide extra binding

sites for the fluoride, in competition with the magnesium in bone.

Rich

>

> Looks llike the damage is from complexing magnesium -

> And if I read this correctly - this is in vitro- and who knows if

Mg

> supplemtation would help in vivo..

>

> A friends horse is about to receive a large dose of Baytrill for an

> e.coli abscess (of pretty long duration) and we're worried about

> flororquinoline tendon damage- now wondering if Mg supplemtation

> will help...

>

> But I guess this is just as applicable to humans- so why don't the

> LLMDs that use these abx- know any of this????

>

> Barb

>

>

>

> : Vet Pathol. 2001 Mar;38(2):143-8. Links

> In vitro evidence for effects of magnesium supplementation on

> quinolone-treated horse and dog chondrocytes.Egerbacher M,

> Wolfesberger B, Gabler C.

> Institute of Histology and Embryology, University of Veterinary

> Medicine, Vienna, Austria.

>

> Quinolones and magnesium deficiency cause similar lesions in joint

> cartilage of young animals. Chondrocytes cultivated in the

presence

> of quinolones and in Mg-free medium show severe alterations in

> cytoskeleton and decreased ability to adhere to the culture dish.

We

> investigated whether Mg2+ supplementation can prevent quinolone-

> mediated effects on chondrocytes in vitro. Chondrocytes cultivated

in

> Dulbecco's modified Eagle's medium/HAM's F-12 medium were treated

> with ciprofloxacin (80 and 160 microg/ml) and enrofloxacin (100

and

> 150 microg/ml). Mg2+ was added at a concentration of 0.0612 mg/ml

> (MgCl) and 0.0488 mg/ml (MgSO4) or a triple dose. In addition,

cells

> were cultivated in Mg-free medium and accordingly treated with

Mg2+

> supplementation. After 5 days in culture, the number of adherent

> cells per milliliter was determined. The number of chondrocytes in

> quinolone-treated groups decreased to 12-36% that of the control

> group within the culture period. With Mg2+ supplementation, the

> number of attached cells increased to 40-70% that of control

cells.

> The threefold dose of Mg2+ led to better results than did the

single

> dose. Cell proliferation tested by immunohistochemical staining

with

> Ki67 (clone MIB5) decreased from 70% in control groups to 55%,

48%,

> and 30% in enrofloxacin-treated groups in a concentration

dependent

> manner (50, 100, and 150 microg/ml). Addition of Mg2+ did not

> increase the rate of cell proliferation.

>

> These results suggest that a great part of quinolone-induced

damage

> is due to magnesium complex formation, as Mg2+ supplementation is

> able to reduce the effects in vitro. However, quinolone effects on

> cell proliferation seem to be an independent process that is not

> influenced by magnesium supplementation

>

[Guest guest]

Rich,

The curious thing is that I got the most help with the tendon pain

when I started Recuperation. It was amazing. Also the CNS damage from

the quinolones was relieved with Recup. Now if I could just figure

out what is wrong with my vestibular nerves - just when I thought I

was out of the woods.

a

>

> Hi, Barb.

>

> Thanks for posting this abstract. I have suspected that the

> fluoroquinolones cause problems with the tendon attachment to bone

> because the flouride binds magnesium at the junction, interfering

> with the adhesion of the tendon. Magnesium fluoride is very

> insoluble, meaning a strong bond forms between magnesium and

> fluoride. I think this is why a seemed to get some relief when

> she supplemented magnesium, since this would provide extra binding

> sites for the fluoride, in competition with the magnesium in bone.

>

> Rich

>

>

>

> >

> > Looks llike the damage is from complexing magnesium -

> > And if I read this correctly - this is in vitro- and who knows if

> Mg

> > supplemtation would help in vivo..

> >

> > A friends horse is about to receive a large dose of Baytrill for

an

> > e.coli abscess (of pretty long duration) and we're worried about

> > flororquinoline tendon damage- now wondering if Mg supplemtation

> > will help...

> >

> > But I guess this is just as applicable to humans- so why don't

the

> > LLMDs that use these abx- know any of this????

> >

> > Barb

> >

> >

> >

> > : Vet Pathol. 2001 Mar;38(2):143-8. Links

> > In vitro evidence for effects of magnesium supplementation on

> > quinolone-treated horse and dog chondrocytes.Egerbacher M,

> > Wolfesberger B, Gabler C.

> > Institute of Histology and Embryology, University of Veterinary

> > Medicine, Vienna, Austria.

> >

> > Quinolones and magnesium deficiency cause similar lesions in

joint

> > cartilage of young animals. Chondrocytes cultivated in the

> presence

> > of quinolones and in Mg-free medium show severe alterations in

> > cytoskeleton and decreased ability to adhere to the culture dish.

> We

> > investigated whether Mg2+ supplementation can prevent quinolone-

> > mediated effects on chondrocytes in vitro. Chondrocytes

cultivated

> in

> > Dulbecco's modified Eagle's medium/HAM's F-12 medium were treated

> > with ciprofloxacin (80 and 160 microg/ml) and enrofloxacin (100

> and

> > 150 microg/ml). Mg2+ was added at a concentration of 0.0612 mg/ml

> > (MgCl) and 0.0488 mg/ml (MgSO4) or a triple dose. In addition,

> cells

> > were cultivated in Mg-free medium and accordingly treated with

> Mg2+

> > supplementation. After 5 days in culture, the number of adherent

> > cells per milliliter was determined. The number of chondrocytes

in

> > quinolone-treated groups decreased to 12-36% that of the control

> > group within the culture period. With Mg2+ supplementation, the

> > number of attached cells increased to 40-70% that of control

> cells.

> > The threefold dose of Mg2+ led to better results than did the

> single

> > dose. Cell proliferation tested by immunohistochemical staining

> with

> > Ki67 (clone MIB5) decreased from 70% in control groups to 55%,

> 48%,

> > and 30% in enrofloxacin-treated groups in a concentration

> dependent

> > manner (50, 100, and 150 microg/ml). Addition of Mg2+ did not

> > increase the rate of cell proliferation.

> >

> > These results suggest that a great part of quinolone-induced

> damage

> > is due to magnesium complex formation, as Mg2+ supplementation is

> > able to reduce the effects in vitro. However, quinolone effects

on

> > cell proliferation seem to be an independent process that is not

> > influenced by magnesium supplementation

> >

>

[Guest guest]

You're welcome Rich.

The 900lb horse has an IV in her neck again and the baytril (20cc/day)

was started today. This is an e.coli abscess that went to the bone-

horse was operated on- bone scraped - and then sutured up.. abscess

came back.

Owners have been dealing within this now for over 6 weeks - 5

different abx (including gentamicin IV, SMZ injection IM, Pennicillin

IM - and another IV I can't remember the name of the abx...

2 cultures have failed to grow anything - but post-OP the culture grew

e.coli. Vet did a sensitivity test and said it was sensitive to

pennicillin (and shouldn't be) was marginally sensitive to gentamicin

(and should be very sensitive) but appeared to be very sensitive to

Baytril - hense the Baytril now IV for 10 days.

It may be a mixed infection... in any case - the horse is on

probiotics and now supplemented with magnesium because of the

flourorquinoline (my influence on the Vet).

The VetMed abstract is the best one I've seen to explain the actual

mechanism to tendon damage with quinolines- guess everyone should be

taking Mg if even thinking about a flouroquinoline. And the young,

and possibly the old shouldn't take them at all. Vets won't give

that chemical class to young animals at all -

In any case - it looks like the vets are ahead of the human MDs again.

(with their knowledge- culturing and abx sensitivity tests..

I hope this horse makes it- she's really nice, and putting up with

this amazingly well (she's confined to a stall when she has the IV

in).

Barb

> >

> > Looks llike the damage is from complexing magnesium -

> > And if I read this correctly - this is in vitro- and who knows if

> Mg

> > supplemtation would help in vivo..

> >

> > A friends horse is about to receive a large dose of Baytrill for

an

> > e.coli abscess (of pretty long duration) and we're worried about

> > flororquinoline tendon damage- now wondering if Mg supplemtation

> > will help...

> >

> > But I guess this is just as applicable to humans- so why don't

the

> > LLMDs that use these abx- know any of this????

> >

> > Barb

> >

> >

> >

> > : Vet Pathol. 2001 Mar;38(2):143-8. Links

> > In vitro evidence for effects of magnesium supplementation on

> > quinolone-treated horse and dog chondrocytes.Egerbacher M,

> > Wolfesberger B, Gabler C.

> > Institute of Histology and Embryology, University of Veterinary

> > Medicine, Vienna, Austria.

> >

> > Quinolones and magnesium deficiency cause similar lesions in

joint

> > cartilage of young animals. Chondrocytes cultivated in the

> presence

> > of quinolones and in Mg-free medium show severe alterations in

> > cytoskeleton and decreased ability to adhere to the culture dish.

> We

> > investigated whether Mg2+ supplementation can prevent quinolone-

> > mediated effects on chondrocytes in vitro. Chondrocytes

cultivated

> in

> > Dulbecco's modified Eagle's medium/HAM's F-12 medium were treated

> > with ciprofloxacin (80 and 160 microg/ml) and enrofloxacin (100

> and

> > 150 microg/ml). Mg2+ was added at a concentration of 0.0612 mg/ml

> > (MgCl) and 0.0488 mg/ml (MgSO4) or a triple dose. In addition,

> cells

> > were cultivated in Mg-free medium and accordingly treated with

> Mg2+

> > supplementation. After 5 days in culture, the number of adherent

> > cells per milliliter was determined. The number of chondrocytes

in

> > quinolone-treated groups decreased to 12-36% that of the control

> > group within the culture period. With Mg2+ supplementation, the

> > number of attached cells increased to 40-70% that of control

> cells.

> > The threefold dose of Mg2+ led to better results than did the

> single

> > dose. Cell proliferation tested by immunohistochemical staining

> with

> > Ki67 (clone MIB5) decreased from 70% in control groups to 55%,

> 48%,

> > and 30% in enrofloxacin-treated groups in a concentration

> dependent

> > manner (50, 100, and 150 microg/ml). Addition of Mg2+ did not

> > increase the rate of cell proliferation.

> >

> > These results suggest that a great part of quinolone-induced

> damage

> > is due to magnesium complex formation, as Mg2+ supplementation is

> > able to reduce the effects in vitro. However, quinolone effects

on

> > cell proliferation seem to be an independent process that is not

> > influenced by magnesium supplementation

> >

>

[Guest guest]

Hmm. If they got into the bone, there could be biofilm cells there,

as have been claimed to exist in human osteomyelitis (according to

papers I have not read). This might mean biofilm-associated

persisters could be present that would be really hard to kill with

drugs and really hard to phagocytose, thus re-seeding the abcess

after withdrawals of treatment. I hope the quinolone works. After

all, quinolones have a rather violent molecular mechanism and have

been seen to be rather on the effective side in some experimental

systems used to study physiologic abx tolerance.

The good sensitivity to the quinolone is also a good sign, but the

cells in the lab culture are unfortunately in a very different

physiological state than persister/tolerant types that may be re-

seeding the relapse.

Your friend might want to consider some kind of multi-month followup

treatment, particularly if there is one that would be quite benign

to the horse. Multi-month abx would be standard in human

osteomyelitis, tho the osteomyelitis medical community seems to

think that success in the bone debridement is really the most

critical point in resolving the human disease. If the immune system

is capable of slowly degrading any biofilm that might be present,

long-term treatment might hold the cells down until this process

wears down the bacterial population to a level insufficient for

reseeding a relapse. Or not. I wonder if there is any empirical data

on how/whether this all works in this type of situation in the horse.

Though moving cells from a horse onto lab madia may often change

their physiology drastically, it won't change their genotype. This

makes it possible to look at how the population genotype might have

changed during treatment. It would be interesting to examine whether

the population gained genetic resistence to any of the agents used.

If not, that would tell you that the cells that survived the abx did

so because of their physiology (unless they were simply shielded

physically from the abx in some way). Of course, its also possible

that the cells that survived did so because of a mix of transient

physiological and permanent genetic traits, in which case lab

results might show that a genetic resistance had been gained, but

only a very weak one.

>

> You're welcome Rich.

> The 900lb horse has an IV in her neck again and the baytril

(20cc/day)

> was started today. This is an e.coli abscess that went to the

bone-

> horse was operated on- bone scraped - and then sutured up..

abscess

> came back.

> Owners have been dealing within this now for over 6 weeks - 5

> different abx (including gentamicin IV, SMZ injection IM,

Pennicillin

> IM - and another IV I can't remember the name of the abx...

>

> 2 cultures have failed to grow anything - but post-OP the culture

grew

> e.coli. Vet did a sensitivity test and said it was sensitive to

> pennicillin (and shouldn't be) was marginally sensitive to

gentamicin

> (and should be very sensitive) but appeared to be very sensitive

to

> Baytril - hense the Baytril now IV for 10 days.

>

> It may be a mixed infection... in any case - the horse is on

> probiotics and now supplemented with magnesium because of the

> flourorquinoline (my influence on the Vet).

>

> The VetMed abstract is the best one I've seen to explain the

actual

> mechanism to tendon damage with quinolines- guess everyone should

be

> taking Mg if even thinking about a flouroquinoline. And the young,

> and possibly the old shouldn't take them at all. Vets won't give

> that chemical class to young animals at all -

>

> In any case - it looks like the vets are ahead of the human MDs

again.

> (with their knowledge- culturing and abx sensitivity tests..

>

> I hope this horse makes it- she's really nice, and putting up with

> this amazingly well (she's confined to a stall when she has the IV

> in).

>

> Barb

>

>

[Guest guest]

Peopl spend 20, 30 50 thousand dollars on their own health care to

avoid death if they have to.

In the case of animals- every owner has a finite $ amount they'll

spend.

They get put down if they get too expensive.

Just the Baytril for the horse (and this is the 4th abx) is $450.00

for 10 days.

Hope this does it for her.

Barb

> >

> > You're welcome Rich.

> > The 900lb horse has an IV in her neck again and the baytril

> (20cc/day)

> > was started today. This is an e.coli abscess that went to the

> bone-

> > horse was operated on- bone scraped - and then sutured up..

> abscess

> > came back.

> > Owners have been dealing within this now for over 6 weeks - 5

> > different abx (including gentamicin IV, SMZ injection IM,

> Pennicillin

> > IM - and another IV I can't remember the name of the abx...

> >

> > 2 cultures have failed to grow anything - but post-OP the culture

> grew

> > e.coli. Vet did a sensitivity test and said it was sensitive to

> > pennicillin (and shouldn't be) was marginally sensitive to

> gentamicin

> > (and should be very sensitive) but appeared to be very sensitive

> to

> > Baytril - hense the Baytril now IV for 10 days.

> >

> > It may be a mixed infection... in any case - the horse is on

> > probiotics and now supplemented with magnesium because of the

> > flourorquinoline (my influence on the Vet).

> >

> > The VetMed abstract is the best one I've seen to explain the

> actual

> > mechanism to tendon damage with quinolines- guess everyone should

> be

> > taking Mg if even thinking about a flouroquinoline. And the

young,

> > and possibly the old shouldn't take them at all. Vets won't give

> > that chemical class to young animals at all -

> >

> > In any case - it looks like the vets are ahead of the human MDs

> again.

> > (with their knowledge- culturing and abx sensitivity tests..

> >

> > I hope this horse makes it- she's really nice, and putting up

with

> > this amazingly well (she's confined to a stall when she has the

IV

> > in).

> >

> > Barb

> >

> >

>