Re: The heart and Minocycline

[Guest guest]

Jelly wrote:

Yes!.. That's one of Mino's non microbial effects..

as far as the IV dose cited in your paper..

3mg/kg IV (a Kg is 2.2 lbs, so for a 150lb person, their weight in

kilograms is about 68Kg x 3mg= 204mg Mino by intravenous.

>

> After a comment that was made about low dose Mino being tough on

the

> heart that freaked me out, and I ran out to look.

>

> This is what I found: Did you know that they often interlace parts

> being used on the heart with Minocycline and Rifampin????

> ====================================================================

>

> Background

> Minocycline, a semi-synthetic tetracycline antibiotic, is an

> effective neuroprotective agent in animal models of cerebral

> ischemia when given in high doses intraperitoneally. The aim of

this

> study was to determine if minocycline was effective at reducing

> infarct size in a Temporary Middle Cerebral Artery Occlusion model

> (TMCAO) when given at lower intravenous (IV) doses that correspond

> to human clinical exposure regimens.

>

>

> Methods

> Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo

> was administered IV starting at 4, 5, or 6 hours post TMCAO.

Infarct

> volume and neurofunctional tests were carried out at 24 hr after

> TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain

staining

> and Neurological Score evaluation. Pharmacokinetic studies and

> hemodynamic monitoring were performed on minocycline-treated rats.

>

>

> Results

> Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at

> reducing infarct size when administered at 4 hours post TMCAO. At

> doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10

> mg/kg reduced infarct size by 56%. Minocycline at a dose of 10

mg/kg

> significantly reduced infarct size at 5 hours by 40% and the 3

mg/kg

> dose significantly reduced infarct size by 34%. With a 6 hour time

> window there was a non-significant trend in infarct reduction.

There

> was a significant difference in neurological scores favoring

> minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and

at

> the 10 mg/kg dose at 5 hours. Minocycline did not significantly

> affect hemodynamic and physiological variables. A 3 mg/kg IV dose

of

> minocycline resulted in serum levels similar to that achieved in

> humans after a standard 200 mg dose.

>

>

> Conclusions

> The neuroprotective action of minocycline at clinically suitable

> dosing regimens and at a therapeutic time window of at least 4–5

> hours merits consideration of phase I trials in humans in view of

> developing this drug for treatment of stroke.

> ==================================================================

>

> From Wayne State University of Pharmecology:

>

> Minocycline as a new cardioprotective agent

> We also investigated the cardioprotective effects of minocycline in

> primary cultures of both neonatal and adult cardiac myocytes as

well

> as in the intact heart. Minocycline is a second-generation

> tetracycline with proven safety that is used in humans for the

> treatment of acne and urethritis as well as of severe chronic

> inflammatory diseases. Our report showed that minocycline

> significantly reduced the post-ischemic occurrence of necrotic and

> apoptotic cell death, with normalization of developed and diastolic

> pressure. In regard to its antiapoptotic mechanism of action, we

> observed that minocycline reduced the expression level of initiator

> caspases, increased the ratio of XIAP to Smac/DIABLO at both the

> mRNA and protein level, and prevented the mitochondria-mediated

> release of cytochrome c and Smac/DIABLO. These synergistic actions

> dramatically reduced the post-ischemic induction of caspase

activity

> associated with cardiac ischemia/reperfusion injury. Owing to its

> safety record and multiple novel mechanisms of action, minocycline

> may be a valuable cardioprotective agent to ameliorate the cardiac

> dysfunction and cell loss associated with acute and chronic

ischemia

> reperfusion injury.

>

> ===============================================================

>

> So Mino seems theraputic for the heart, but what about small doses

> taken orally is still the question?

>

[Guest guest]

I'm wondering if symptoms of dysautonomia are somehow exacerbated by

Minocin. Tachycardia, hypotension, irregularities, thermo-dysregulation

etc. Maybe Minocin increases irritability of autonomic nervous system?

Both Jelly and I have MVP, does Minocin have an effect on the ANS? I

couldn't find anything....

Robyn

[Guest guest]

Did you understand the 3 to 10 mg per kg of weight thing. I would

have to take between 300 and 900 mg's to fall into place with the

study

>

> After a comment that was made about low dose Mino being tough on

the

> heart that freaked me out, and I ran out to look.

>

> This is what I found: Did you know that they often interlace parts

> being used on the heart with Minocycline and Rifampin????

>

====================================================================

>

> Background

> Minocycline, a semi-synthetic tetracycline antibiotic, is an

> effective neuroprotective agent in animal models of cerebral

> ischemia when given in high doses intraperitoneally. The aim of

this

> study was to determine if minocycline was effective at reducing

> infarct size in a Temporary Middle Cerebral Artery Occlusion model

> (TMCAO) when given at lower intravenous (IV) doses that correspond

> to human clinical exposure regimens.

>

>

> Methods

> Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo

> was administered IV starting at 4, 5, or 6 hours post TMCAO.

Infarct

> volume and neurofunctional tests were carried out at 24 hr after

> TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain

staining

> and Neurological Score evaluation. Pharmacokinetic studies and

> hemodynamic monitoring were performed on minocycline-treated rats.

>

>

> Results

> Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at

> reducing infarct size when administered at 4 hours post TMCAO. At

> doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10

> mg/kg reduced infarct size by 56%. Minocycline at a dose of 10

mg/kg

> significantly reduced infarct size at 5 hours by 40% and the 3

mg/kg

> dose significantly reduced infarct size by 34%. With a 6 hour time

> window there was a non-significant trend in infarct reduction.

There

> was a significant difference in neurological scores favoring

> minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and

at

> the 10 mg/kg dose at 5 hours. Minocycline did not significantly

> affect hemodynamic and physiological variables. A 3 mg/kg IV dose

of

> minocycline resulted in serum levels similar to that achieved in

> humans after a standard 200 mg dose.

>

>

> Conclusions

> The neuroprotective action of minocycline at clinically suitable

> dosing regimens and at a therapeutic time window of at least 4–5

> hours merits consideration of phase I trials in humans in view of

> developing this drug for treatment of stroke.

> ==================================================================

>

> From Wayne State University of Pharmecology:

>

> Minocycline as a new cardioprotective agent

> We also investigated the cardioprotective effects of minocycline

in

> primary cultures of both neonatal and adult cardiac myocytes as

well

> as in the intact heart. Minocycline is a second-generation

> tetracycline with proven safety that is used in humans for the

> treatment of acne and urethritis as well as of severe chronic

> inflammatory diseases. Our report showed that minocycline

> significantly reduced the post-ischemic occurrence of necrotic and

> apoptotic cell death, with normalization of developed and

diastolic

> pressure. In regard to its antiapoptotic mechanism of action, we

> observed that minocycline reduced the expression level of

initiator

> caspases, increased the ratio of XIAP to Smac/DIABLO at both the

> mRNA and protein level, and prevented the mitochondria-mediated

> release of cytochrome c and Smac/DIABLO. These synergistic actions

> dramatically reduced the post-ischemic induction of caspase

activity

> associated with cardiac ischemia/reperfusion injury. Owing to its

> safety record and multiple novel mechanisms of action, minocycline

> may be a valuable cardioprotective agent to ameliorate the cardiac

> dysfunction and cell loss associated with acute and chronic

ischemia

> reperfusion injury.

>

> ===============================================================

>

> So Mino seems theraputic for the heart, but what about small doses

> taken orally is still the question?

>

[Guest guest]

Not the weight part, but I did catch this " A 3 mg/kg IV dose

of

> minocycline resulted in serum levels similar to that achieved in

> humans after a standard 200 mg dose. "

> >

> > After a comment that was made about low dose Mino being tough on

> the

> > heart that freaked me out, and I ran out to look.

> >

> > This is what I found: Did you know that they often interlace

parts

> > being used on the heart with Minocycline and Rifampin????

> >

>

====================================================================

> >

> > Background

> > Minocycline, a semi-synthetic tetracycline antibiotic, is an

> > effective neuroprotective agent in animal models of cerebral

> > ischemia when given in high doses intraperitoneally. The aim of

> this

> > study was to determine if minocycline was effective at reducing

> > infarct size in a Temporary Middle Cerebral Artery Occlusion

model

> > (TMCAO) when given at lower intravenous (IV) doses that

correspond

> > to human clinical exposure regimens.

> >

> >

> > Methods

> > Rats underwent 90 minutes of TMCAO. Minocycline or saline

placebo

> > was administered IV starting at 4, 5, or 6 hours post TMCAO.

> Infarct

> > volume and neurofunctional tests were carried out at 24 hr after

> > TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain

> staining

> > and Neurological Score evaluation. Pharmacokinetic studies and

> > hemodynamic monitoring were performed on minocycline-treated

rats.

> >

> >

> > Results

> > Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at

> > reducing infarct size when administered at 4 hours post TMCAO.

At

> > doses of 3 mg/kg, minocycline reduced infarct size by 42% while

10

> > mg/kg reduced infarct size by 56%. Minocycline at a dose of 10

> mg/kg

> > significantly reduced infarct size at 5 hours by 40% and the 3

> mg/kg

> > dose significantly reduced infarct size by 34%. With a 6 hour

time

> > window there was a non-significant trend in infarct reduction.

> There

> > was a significant difference in neurological scores favoring

> > minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours

and

> at

> > the 10 mg/kg dose at 5 hours. Minocycline did not significantly

> > affect hemodynamic and physiological variables. A 3 mg/kg IV

dose

> of

> > minocycline resulted in serum levels similar to that achieved in

> > humans after a standard 200 mg dose.

> >

> >

> > Conclusions

> > The neuroprotective action of minocycline at clinically suitable

> > dosing regimens and at a therapeutic time window of at least 4–5

> > hours merits consideration of phase I trials in humans in view

of

> > developing this drug for treatment of stroke.

> >

==================================================================

> >

> > From Wayne State University of Pharmecology:

> >

> > Minocycline as a new cardioprotective agent

> > We also investigated the cardioprotective effects of minocycline

> in

> > primary cultures of both neonatal and adult cardiac myocytes as

> well

> > as in the intact heart. Minocycline is a second-generation

> > tetracycline with proven safety that is used in humans for the

> > treatment of acne and urethritis as well as of severe chronic

> > inflammatory diseases. Our report showed that minocycline

> > significantly reduced the post-ischemic occurrence of necrotic

and

> > apoptotic cell death, with normalization of developed and

> diastolic

> > pressure. In regard to its antiapoptotic mechanism of action, we

> > observed that minocycline reduced the expression level of

> initiator

> > caspases, increased the ratio of XIAP to Smac/DIABLO at both the

> > mRNA and protein level, and prevented the mitochondria-mediated

> > release of cytochrome c and Smac/DIABLO. These synergistic

actions

> > dramatically reduced the post-ischemic induction of caspase

> activity

> > associated with cardiac ischemia/reperfusion injury. Owing to

its

> > safety record and multiple novel mechanisms of action,

minocycline

> > may be a valuable cardioprotective agent to ameliorate the

cardiac

> > dysfunction and cell loss associated with acute and chronic

> ischemia

> > reperfusion injury.

> >

> > ===============================================================

> >

> > So Mino seems theraputic for the heart, but what about small

doses

> > taken orally is still the question?

> >

>

[Guest guest]

When I am experiencing my negative effects from the Mino, everything

gets worse. Everything increases in intensity comparitivaly to the

dose of Mino I am taking. I have dysatonomia, so it is exascerbated.

My hyperecoagulation gets worse, even when I am on heparin, and I have

had to up the heparin temporarily and then it dropped back down when

stopping the Mino. Raynaud's gets worse, just everything. That is why

I have kept my dose so low and only go up when exagerrated symptoms

settle down. I am able to control the intensity of everything.

-- In infections , " onrwayca "

<mikenrobyn@...> wrote:

>

> I'm wondering if symptoms of dysautonomia are somehow exacerbated by

> Minocin. Tachycardia, hypotension, irregularities, thermo-

dysregulation

> etc. Maybe Minocin increases irritability of autonomic nervous

system?

>

> Both Jelly and I have MVP, does Minocin have an effect on the ANS? I

> couldn't find anything....

>

> Robyn

>

[Guest guest]

Seems therapeutic. It probably all depends on how badly the heart is infected. Underdosing could be bad news, stimulating the bugs and causing them to act up, or a big dose hitting the heart could also be bad news if it causes a big herx. True herxes can be very dangerous. Who knows? But I get nervous when I'm messing with my heart and/or my brain. And minocycline messes with both in my case. Also eyes. I don't necessarily want to go blind. It's funny that, because they make you test your eyes with plaquenil, and the odds of eye damage on that drug are almost nil, and yet minocycline can cause pseudotumor cerebri (intracranial hypertension) which can cause permanent blindness, and you don't have to be tested. Minocycline can also completely mess with your thyroid. I can tell you that there are gazillions of studies involving minocycline. A lot of them are actually scary, which just reaffirmed my conviction to

avoid it because of my reactions to it, but it's obviously a powerful drug one way or another. Just keep researching is my opinion. penny jellybelly92008 <herranenb@...> wrote: After a comment that was made about low dose Mino being tough on the heart that freaked me out, and I ran out to look.This is what I found: Did you know that they often interlace parts being used on the heart with Minocycline and

Rifampin????====================================================================BackgroundMinocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens.MethodsRats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic

monitoring were performed on minocycline-treated rats.ResultsMinocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg

dose.ConclusionsThe neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4–5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke.==================================================================From Wayne State University of Pharmecology:Minocycline as a new cardioprotective agent We also investigated the cardioprotective effects of minocycline in primary cultures of both neonatal and adult cardiac myocytes as well as in the intact heart. Minocycline is a second-generation tetracycline with proven safety that is used in humans for the treatment of acne and urethritis as well as of severe chronic inflammatory diseases. Our report showed that minocycline significantly reduced the post-ischemic occurrence of necrotic and apoptotic cell death,

with normalization of developed and diastolic pressure. In regard to its antiapoptotic mechanism of action, we observed that minocycline reduced the expression level of initiator caspases, increased the ratio of XIAP to Smac/DIABLO at both the mRNA and protein level, and prevented the mitochondria-mediated release of cytochrome c and Smac/DIABLO. These synergistic actions dramatically reduced the post-ischemic induction of caspase activity associated with cardiac ischemia/reperfusion injury. Owing to its safety record and multiple novel mechanisms of action, minocycline may be a valuable cardioprotective agent to ameliorate the cardiac dysfunction and cell loss associated with acute and chronic ischemia reperfusion injury. ===============================================================So Mino seems theraputic for the heart, but what about small doses taken orally is

still the question?