Re: Zithro works to knock out borrelia, not as an immune modulator

[Guest guest]

This is rediculous science IMO. If you had carnitine being such a

remarkable aid in heart disease you'd have the world wide trillion

dollar heart industry chomping at the bit to include this in there

pharmaceutical products? Why do people publish this stuff as factual

and deceive the patient. We have a whole other forum that is using

garlic and half a dozen other concoctions as there antimicrobial to

get their infections under control.. Then there using all these

supplements that are supposedly fixing stuff like these types of

articles on carnitine suggest. The problem is then it becomes

factual.Then you have everyone flogging dead horse therapies for

twqenty year stretches, basically rehatching garbage.. We just had

Barb describe what you need to do to get the junk out of your blood.

(dialysis) I tend to follow a regime like the biggest looser where I

spend an hour on the exercise bike sweating profusely and HOPEFULLY

PUMPING MY BLOOD full of oxygen to clean it.

>

> Azithromycin in Chronic Fatigue Syndrome (CFS)

> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

> an analysis of clinical data

>

> Authors: Ruud CW Vermeulen and Hans R Scholte

>

> Journal of Translational Medicine 2006, 4:34

> doi:10.1186/1479-5876-4-34

>

> Published 15 August 2006

>

>

> Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of

> clinical data

>

> Ruud C.W. Vermeulen*1 and Hans R. Scholte2

> Address: 1CFS and Pain Research Center Amsterdam, Waalstraat 25-31,

> 1078 BR Amsterdam, The Netherlands, 2Department of Biochemistry,

> Erasmus MC-University Medical Center Rotterdam, Rotterdam, The

> Netherlands.

>

> E-mail: Ruud CW Vermeulen* - rv@...;

> Hans R Scholte h.scholte@...

> * Corresponding author

>

>

> Abstract

>

> Background: CFS is a clinical state with defined symptoms, but

> undefined cause. The patients may show a chronic state of immune

> activation and treatment with an antibiotic in this subgroup has

been

> suggested.

>

> Methods:

>

> In a retrospective study, the response of CFS patients to

> azithromycin, an antibiotic and immunomodulating drug, has been

> scored from the patients records and compared with clinical and

> laboratory data. Azithromycin was not the first choice therapy, but

> offered when the effect of counseling and L-carnitine was

considered

> insufficient by the patient and the clinician.

>

> Results:

>

> Of the 99 patients investigated, 58 reported a decrease in the

> symptoms by the use of azithromycin. These responding patients had

> lower levels of plasma acetylcarnitine.

>

> Conclusion:

>

> The efficacy of azithromycin in the responsive patients could be

> explained by the modulating effect on a chronic primed state of the

> immune cells of the brain, or the activated peripheral immune

system.

> Their lower acetylcarnitine levels may reflect a decreased

> antioxidant defense and/or an increased consumption of

> acetylcarnitine caused by oxidative stress.

>

>

>

> Background

>

> In 1994 Fukuda et al. [1] defined CFS as a chronic persistent

fatigue

> that is present for over 6 months, is not caused by activity nor

> alleviated by rest and accompanied with at least 4 other

> symptoms: cognitive impairment, pain in joints, muscles or head,

> unrefreshing sleep, soar throat, tender lymph nodes and

> postexertional malaise with slow recovery. Nevertheless, CFS

remained

> subject to debate and even the mere existence of the syndrome was

> still questioned by some. The presentation of the results of

> quantitative morphology of the brain in CFS patients by Okada et al

> [2], later confirmed by De Lange et al [3] may change this opinion.

> The loss of grey matter in the brain, especially in Brodmanns area

> 9, was related to physical impairment, but not to the duration of

the

> symptoms. Although other explanations were considered as well, this

> may indicate the occurrence of a major trauma to the brain at the

> start of the disease. This could also explain the low recovery rate

> in adults, because repair in adult brain is limited [4].

>

>

> The severity of the sickness, both the symptoms and the lowered

> adaptation to physical stress, may fluctuate whenever infections

and

> stress come and go. The Th1 to Th2 cytokine shift in CFS patients

> will make them more vulnerable to infections [5] and it has been

> suggested that they have more often chronic infections [6-8]. The

> predisposition for acquiring CFS may be genetically determined [9,

> 10], the occurrence is influenced by the severity of the immune

> response [11]. The result is a chronic hyper-oxidative state of

> sickness [12, 13], in the brain itself [14] that cannot be stopped

> [15]. Preliminary evidence of a relation between post-infectious

> fatigue and mitochondrial dysfunction indicates a complex response

> involving acetylcarnitine [16].

>

>

> The clinical presentation of the symptoms and chances for recovery

> will depend on the balance between the irreversible loss of grey

> cells and activation of the immune system.

> According to De Meirleir et al, the presence of RNase-L and

elastase

> may offer an indication for this balance [17-19].

> Several treatment protocols to counteract the immune activation in

> CFS were presented [18, 20, 21], but the results were never

validated

> in a double blind study. Such proof is required as a rationale for

> treatment and provides a basis to understand the pathophysiology of

> the disease. Comparing the outcome of clinical treatment protocols

> might add to our knowledge of CFS and its treatment until double

> blind studies are available [22] .

>

>

> Azithromycin is an antibiotic with immunomodulatory effects [23-

25].

> This antibiotic has been successfully used during periods of six

> months of more in other chronic diseases [26-28].

> The side-effects are known for long term use and mainly limited to

> gastro-intestinal cramps. The chances for resistance limit its use

to

> individual patients under close supervision [28]. The drug is

> relatively inexpensive and extensive laboratory tests for side

> effects are not necessary. The result of a study in 10 CFS patients

> during 1 to 2 months was positive [26]. We studied the medical

> records of CFS patients for clinical and laboratory data related to

> the outcome of the treatment with azithromycin.

>

>

>

> http://www.fimdefelice.org/archives/arc.comment3_13_03bioter.html

>

>

>

>

>

> 411 North Avenue East, Cranford, New Jersey 07016-2436 Telephone

> (908) 272-2967 - Fax (908) 272-4589 www.fimdefelice.org

>

> March 13, 2003

>

>

> Bioterrorism: The Potential Role of L-Acetylcarnitine in the

> Treatment of Sepsis and Septic Shock

>

>

> L. DeFelice M.D.

>

> During the Vietnam war, Major Vick, a cardiovascular

> pharmacologist, and I conducted a series of laboratory studies at

the

> Walter Army Institute of Research (WRAIR) which demonstrated

> that carnitine dramatically prevented or reversed myocardial

> ischemia, a lack of oxygen to the heart.

>

> Following these studies, we decided to conduct other laboratory

> studies on whether carnitine could block lethal doses of certain

> toxins. We evaluated primarily cardiovascular effects and survival.

> Some of these studies were conducted at other facilities.

>

> ly speaking, our hopes of success were not that high, but we

> thought that, given carnitine's effect on protecting the heart

> against a lack of oxygen, it was worth a try. We also had read that

> other investigators had demonstrated that carnitine protects

against

> lethal doses of diphtheria toxin in animals.

>

> Then came the unexpected surprise. Carnitine, when given as

> treatment, after the toxicity process was in full swing, reversed

the

> toxicity of the lethal doses of E.coli bacterial toxin, 's

> Viper venom, palytoxin and adriamycin in almost all of the animals

> and other laboratory experimental models such as isolated hearts.

>

> Excited by these findings, I contacted a number of pharmaceutical

> companies about carnitine's potential for the treatment of sepsis

and

> septic shock which is increasingly common in hospitals. I ran into

a

> stone wall mainly because of the absence of a strong carnitine

> patent. Our colleagues in the government expressed interest, but

the

> opportunity somehow fell through the cracks. It was probably due to

> the fact that, because of urgency of the Vietnam war, almost

> everybody in those days was trying mightily to find therapies to

> counter malaria infection and radiation damage. The bioterrorism

> threat was not yet a significant national issue.

>

> I had no choice but to set aside this project, but Major Vick

> continued to conduct other laboratory studies with carnitine with

> exciting results.

>

> I then decided to pursue carnitine for the medical condition of

> myocardial ischemia where the animal data continued to be highly

> promising. After communicating with approximately thirty U.S. and

> international pharmaceutical companies, I met Dr. Claudio Cavazza,

> the proprietor of the privately held, research-oriented Italian

> pharmaceutical company, Sigma-tau S.p.A.

>

> Based on biochemical as well as pharmacological data, he became

> convinced of carnitine's broad medical potential, and invested, and

> has continued to invest, substantial amounts of money in basic and

> clinical research including the development of related molecules

such

> as l-acetylcarnitine and proprionylcarnitine.

>

> Time passed and we paused different paths for awhile. When,

however,

> the anthrax scare burst on the national scene and the real

> possibility that bioterrorism agents which cause septic shock could

> be used as weapons of mass destruction, I became somewhat alarmed.

I

> then called Dr. Cavazza to discuss this situation and was very

happy

> with what I heard.

>

> In the past, some preliminary laboratory studies in septic shock

with

> l-acetylcarnitine were conducted with promising results. For

example,

> one study reported that l-acetylcarnitine could significantly block

> the lethal dose of the bacterial endotoxin substance, LPS.

>

> In addition, two preliminary clinical studies were done in patients

> with septic shock with encouraging results.

>

> In the first study, l-acetylcarnitine was administered

intravenously

> and found to improve the metabolism of body fuel substrates such as

> fatty acids and branched-chain amino acids. In septic shock

patients,

> the mitochondria, the energy producing parts of the cell, are

> compromised. Also, there is an increase in blood coagulation, which

> reduces the blood supply to body tissues and, therefore, much

needed

> oxygen to the cells. This further compromises mitochondrial

function

> leading to a decrease in the cells'

> metabolic capacity to generate fuel not only to maintain normal

> functioning cells but also to keep them alive. Despite the

seriously

> compromised mitochondria and significant decreased in energy

output,

> l-acetylcarnitine managed to increase cellular production of

energy.1

>

> A preliminary double-blind clinical study was conducted in patients

> with septic shock. Both during and after the infusion of l-

> acetylcarnitine both systolic and diastolic blood pressure were

> significantly elevated. Also, the clinical investigations reported

> and improvement in blood oxygenation.2

>

> Now let's switch gears to some interesting recent findings

regarding

> the central nervous system, l-acetylcarnitine and septic shock

> patients.

>

> Because of promising scientific data, Dr. Cavazza decided to

develop

> acetyl-carnitine for medical conditions that involve the central

> nervous system, or brain, as well as the peripheral nervous system.

> In addition to having the cardioprotective effects of carnitine, l-

> acetylcarnitine offers additional benefits by protecting nerve

cells

> when they are seriously challenged.

>

> Drs. Wesley Ely and other experts in shock management at the

> Vanderbilt University Medical Center found that delirium, which is

> common in septic shock, is an indicator or prognosticator of

certain

> clinical outcomes or how well or poorly a patient does.3-4

>

> It is not commonly appreciated that septic shock patients who

managed

> to survive the life-threatening crisis have serious debilitating

> clinical sequelae, including those involving the central nervous

> system. They found that the degree of these debilitating central

> nervous system effects were proportional to the severity and

duration

> of the delirium. Also, the more severe the delirium, the lower the

> survival rate and the duration in the hospital is significantly

> longer.

>

> These data suggest that there is a real possibility that the brain

> may play a major role in septic shock.

>

> There are a number of laboratory studies that report that l-

> acetylcarnitine is an active molecule in the brain. For example, a

> study was conducted in dogs to determine whether carnitine and l-

> acetylcarnitine protected the dog brain after it was deprived of

> oxygen by inducing cardiac arrest. It was found that l-

> acetylcarnitine significantly reversed the neurologic deleterious

> effects of oxygen deprival, while carnitine did not. The

> investigators conclude that l-acetylcarnitine works by restoring

the

> brain's normal aerobic or oxygen-based metabolism, normalizing the

> production of ATP, or cell energy.5

>

> Similar brain protecting properties of l-acetylcaritine against

> oxygen deprivation in rats has also been reported.

>

> The brain effects of l-acetylcarnitine have not yet been studied in

> septic shock animal models or patients. We do know, however, that

it

> crosses the blood-brain barrier in humans. It stimulates the

> production of plasma cortisol and endorphins and increases cerebral

> blood flow to certain parts of the brain. It has also been reported

> to benefit patients with certain diseases of the nervous system.

>

> L-acetylcarnitine's combined cardiovascular and central nervous

> system properties offer promise to septic shock patients. I have

> consulted with a group of experts who, after evaluating all the

> promising pieces of evidence, agreed that it is worthy of a

clinical

> trial in such patients.

>

> There are approximately 750,000 cases of severe sepsis a year, with

> about a thirty-three percent mortality rate. Septic shock now kills

> more patients per year than breast, colon, pancreatic and prostate

> cancers combined!

>

> It is important to note that bioterrorism toxic agents cause septic

> shock or damage the brain or do both. In my opinion, the

possibility

> that l-acetylcarnitine may counter some of these toxic effects

should

> be pursued either alone or in combination with other promising

agents.

>

>

> References:

>

> Gasparetto A., Corbucci G.G., DeBlasi R.A., Antonelli M., Baqiella

> E., D'eddio S., Trevisani C.: Influence of acetyl-carnitine

infusion

> on haemodynamic parameters and survival of circulatory-shock

> patients. INT.J. CLIN.

> PHARM.RESX1(2)83-92 (1991)

>

> Nanni G., Pittiruti M., Giovannini I., Boldrini G., Ronconi P.,

> Castagneto

> M.: Plasma carnitine levels and urinary excretion during sepsis.

> JPEN9: 483-490, 1985

>

> Ely, E.W., , J., Shinitani, G.S., May, L., Truman, B.,

Dittus,

> B., Gautam. S., Bernard, G., Speroff, T., Hart R. Long-term

> neuropsychological deficits following delirium in mechanically

> ventilated ICU patients. Am. J.

> Respir. Crit. Care Med. 165(8):A30, 2002. (now in press at Crit

Care

> Medicine after peer review)

>

> Ely, E.W., Shintani, A., Bernanrd, G., ., J., Gordon, S.,

May,

> L., Truman, B., Gautam, S., Inouye, S., Dittus, B., Speroff, T.

> Delirium in the ICU is associated with prolonged length of stay in

> the hospital and higher mortality. Am J. Respir. Crit Care Med. 165

> (8):A23, 2002. (now under review at NEJM)

>

> Rosenthal, R.E., , R., Wells W., Fiskum, G., Post-ischemic

> administration of acetyl-l-carnitine (ALCAR) prevents neurological

> injury following prolonged cardiac arrest in dogs, Abstract No.

DV9,

> Pharm. Of Cerebral Ischemia '92, Marburg, Germany (1992).

>

>

>

>

>

> 1: Infection. 1993 Mar-Apr;21(2):83-8. Related Articles, Links

>

>

>

> Azithromycin versus doxycycline for treatment of erythema

migrans:

>

> clinical and microbiological findings.

>

>

>

> Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V,

Jereb

> M.

>

>

>

> Department of Infectious Diseases, University Medical Center,

> Ljubljana, Slovenia.

>

>

>

> The effectiveness of azithromycin and doxycycline in the

> treatment of erythema migrans was compared in a prospective

> randomized trial. One hundred seven adult patients with typical

> erythema migrans, examined in the Lyme Borreliosis Outpatients'

> Clinic, University Department of Infectious Diseases in Ljubljana,

> were included in the study. Fifty-five patients received

azithromycin

> (500 mg twice daily for the first day, followed by 500 mg once

daily

> for four days) and 52 patients received doxycycline (100 mg twice

> daily for 14 days). The mean duration of skin lesions after the

> beginning of treatment was 7.5 +/- 5.9 days (median value 5, range

2-

> 28

>

> days) in the azithromycin group and 11.4 +/- 7.8 days (median value

> 9, range

>

> 2 days--8 weeks) in the doxycycline group (p < 0.05). Borrelia

> burgdorferi was isolated from erythema migrans in 28 patients

before

> therapy: in 13 out of 52 in the doxycycline group and in 15 out of

55

> in the azithromycin group. Three months after therapy, the culture

> was positive in four out of

>

> 13 patients treated with doxycycline and in one of the 15 patients

> who received azithromycin. A biopsy was repeated in all the

patients

> with a positive isolation from the first skin specimen. During the

> first 12 months'

>

> follow-up, three patients treated with doxycycline but none in the

> azithromycin group developed major manifestations of Lyme

> borreliosis, while

>

> 15 doxycycline recipients and 10 azithromycin recipients developed

> minor consecutive manifestations.

>

>

>

> Publication Types:

>

>

>

> * Clinical Trial

>

> * Randomized Controlled Trial

>

>

>

>

>

> PMID: 8387966 [PubMed - indexed for MEDLINE]

>

[Guest guest]

Very interesting studies. Thanks! I had just been debating whether to

order some l-acetylcarnitine. Can't get it here in Canada. I think I

will give the Zith study to my GP, even though he still refuses to do

anything beyond established guidelines. This will at least get his

goat (we seem to have a little game going, as each time I go in he

has some annoying parable like how he routinely pushes past pain

while jogging, so why can't I -- never mind that my joints swell up

if I run!).

- Kate

On Aug 18, 2006, at 10:54 PM, pjeanneus wrote:

> Azithromycin in Chronic Fatigue Syndrome (CFS)

> an analysis of clinical data

> Bioterrorism: The Potential Role of L-Acetylcarnitine in the

> Treatment of Sepsis and Septic Shock

[Guest guest]

On Aug 18, 2006, at 10:54 PM, pjeanneus wrote:

> Azithromycin in Chronic Fatigue Syndrome (CFS)

> ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

> an analysis of clinical data

>

> The clinical presentation of the symptoms and chances for recovery

> will depend on the balance between the irreversible loss of grey

> cells and activation of the immune system.

> According to De Meirleir et al, the presence of RNase-L and elastase

> may offer an indication for this balance [17-19].

Okay, I was just trying to understand elastase. I got the general

impression that the body tries to kill Bb with it, but also that it

breaks down cartilage etc, which is bad because it gets upregulated

in Lyme. Do I have that right? What is it that De Meirleir says about

it?

- Kate

[Guest guest]

Tony,Tony,Tony, you missed my point. I was pushing Zithromax, as

usual, and trying to demonstrate that it was probably killing

bacteria in the brain, not just somehow raising carnitine levels.

Hey, you know I am not a supplement pusher.

a

>

> This is rediculous science IMO. If you had carnitine being such a

> remarkable aid in heart disease you'd have the world wide trillion

> dollar heart industry chomping at the bit to include this in there

> pharmaceutical products? Why do people publish this stuff as

factual

> and deceive the patient. We have a whole other forum that is using

> garlic and half a dozen other concoctions as there antimicrobial to

> get their infections under control.. Then there using all these

> supplements that are supposedly fixing stuff like these types of

> articles on carnitine suggest. The problem is then it becomes

> factual.Then you have everyone flogging dead horse therapies for

> twqenty year stretches, basically rehatching garbage.. We just had

> Barb describe what you need to do to get the junk out of your blood.

> (dialysis) I tend to follow a regime like the biggest looser where

I

> spend an hour on the exercise bike sweating profusely and HOPEFULLY

> PUMPING MY BLOOD full of oxygen to clean it.

>

>

>

>

>

> >

> > Azithromycin in Chronic Fatigue Syndrome (CFS)

> > ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

> > an analysis of clinical data

> >

> > Authors: Ruud CW Vermeulen and Hans R Scholte

> >

> > Journal of Translational Medicine 2006, 4:34

> > doi:10.1186/1479-5876-4-34

> >

> > Published 15 August 2006

> >

> >

> > Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of

> > clinical data

> >

> > Ruud C.W. Vermeulen*1 and Hans R. Scholte2

> > Address: 1CFS and Pain Research Center Amsterdam, Waalstraat 25-

31,

> > 1078 BR Amsterdam, The Netherlands, 2Department of Biochemistry,

> > Erasmus MC-University Medical Center Rotterdam, Rotterdam, The

> > Netherlands.

> >

> > E-mail: Ruud CW Vermeulen* - rv@;

> > Hans R Scholte h.scholte@

> > * Corresponding author

> >

> >

> > Abstract

> >

> > Background: CFS is a clinical state with defined symptoms, but

> > undefined cause. The patients may show a chronic state of immune

> > activation and treatment with an antibiotic in this subgroup has

> been

> > suggested.

> >

> > Methods:

> >

> > In a retrospective study, the response of CFS patients to

> > azithromycin, an antibiotic and immunomodulating drug, has been

> > scored from the patients records and compared with clinical and

> > laboratory data. Azithromycin was not the first choice therapy,

but

> > offered when the effect of counseling and L-carnitine was

> considered

> > insufficient by the patient and the clinician.

> >

> > Results:

> >

> > Of the 99 patients investigated, 58 reported a decrease in the

> > symptoms by the use of azithromycin. These responding patients

had

> > lower levels of plasma acetylcarnitine.

> >

> > Conclusion:

> >

> > The efficacy of azithromycin in the responsive patients could be

> > explained by the modulating effect on a chronic primed state of

the

> > immune cells of the brain, or the activated peripheral immune

> system.

> > Their lower acetylcarnitine levels may reflect a decreased

> > antioxidant defense and/or an increased consumption of

> > acetylcarnitine caused by oxidative stress.

> >

> >

> >

> > Background

> >

> > In 1994 Fukuda et al. [1] defined CFS as a chronic persistent

> fatigue

> > that is present for over 6 months, is not caused by activity nor

> > alleviated by rest and accompanied with at least 4 other

> > symptoms: cognitive impairment, pain in joints, muscles or head,

> > unrefreshing sleep, soar throat, tender lymph nodes and

> > postexertional malaise with slow recovery. Nevertheless, CFS

> remained

> > subject to debate and even the mere existence of the syndrome was

> > still questioned by some. The presentation of the results of

> > quantitative morphology of the brain in CFS patients by Okada et

al

> > [2], later confirmed by De Lange et al [3] may change this

opinion.

> > The loss of grey matter in the brain, especially in Brodmanns

area

> > 9, was related to physical impairment, but not to the duration of

> the

> > symptoms. Although other explanations were considered as well,

this

> > may indicate the occurrence of a major trauma to the brain at the

> > start of the disease. This could also explain the low recovery

rate

> > in adults, because repair in adult brain is limited [4].

> >

> >

> > The severity of the sickness, both the symptoms and the lowered

> > adaptation to physical stress, may fluctuate whenever infections

> and

> > stress come and go. The Th1 to Th2 cytokine shift in CFS patients

> > will make them more vulnerable to infections [5] and it has been

> > suggested that they have more often chronic infections [6-8]. The

> > predisposition for acquiring CFS may be genetically determined

[9,

> > 10], the occurrence is influenced by the severity of the immune

> > response [11]. The result is a chronic hyper-oxidative state of

> > sickness [12, 13], in the brain itself [14] that cannot be

stopped

> > [15]. Preliminary evidence of a relation between post-infectious

> > fatigue and mitochondrial dysfunction indicates a complex

response

> > involving acetylcarnitine [16].

> >

> >

> > The clinical presentation of the symptoms and chances for

recovery

> > will depend on the balance between the irreversible loss of grey

> > cells and activation of the immune system.

> > According to De Meirleir et al, the presence of RNase-L and

> elastase

> > may offer an indication for this balance [17-19].

> > Several treatment protocols to counteract the immune activation

in

> > CFS were presented [18, 20, 21], but the results were never

> validated

> > in a double blind study. Such proof is required as a rationale

for

> > treatment and provides a basis to understand the pathophysiology

of

> > the disease. Comparing the outcome of clinical treatment

protocols

> > might add to our knowledge of CFS and its treatment until double

> > blind studies are available [22] .

> >

> >

> > Azithromycin is an antibiotic with immunomodulatory effects [23-

> 25].

> > This antibiotic has been successfully used during periods of six

> > months of more in other chronic diseases [26-28].

> > The side-effects are known for long term use and mainly limited

to

> > gastro-intestinal cramps. The chances for resistance limit its

use

> to

> > individual patients under close supervision [28]. The drug is

> > relatively inexpensive and extensive laboratory tests for side

> > effects are not necessary. The result of a study in 10 CFS

patients

> > during 1 to 2 months was positive [26]. We studied the medical

> > records of CFS patients for clinical and laboratory data related

to

> > the outcome of the treatment with azithromycin.

> >

> >

> >

> > http://www.fimdefelice.org/archives/arc.comment3_13_03bioter.html

> >

> >

> >

> >

> >

> > 411 North Avenue East, Cranford, New Jersey 07016-2436 Telephone

> > (908) 272-2967 - Fax (908) 272-4589 www.fimdefelice.org

> >

> > March 13, 2003

> >

> >

> > Bioterrorism: The Potential Role of L-Acetylcarnitine in the

> > Treatment of Sepsis and Septic Shock

> >

> >

> > L. DeFelice M.D.

> >

> > During the Vietnam war, Major Vick, a cardiovascular

> > pharmacologist, and I conducted a series of laboratory studies at

> the

> > Walter Army Institute of Research (WRAIR) which demonstrated

> > that carnitine dramatically prevented or reversed myocardial

> > ischemia, a lack of oxygen to the heart.

> >

> > Following these studies, we decided to conduct other laboratory

> > studies on whether carnitine could block lethal doses of certain

> > toxins. We evaluated primarily cardiovascular effects and

survival.

> > Some of these studies were conducted at other facilities.

> >

> > ly speaking, our hopes of success were not that high, but we

> > thought that, given carnitine's effect on protecting the heart

> > against a lack of oxygen, it was worth a try. We also had read

that

> > other investigators had demonstrated that carnitine protects

> against

> > lethal doses of diphtheria toxin in animals.

> >

> > Then came the unexpected surprise. Carnitine, when given as

> > treatment, after the toxicity process was in full swing, reversed

> the

> > toxicity of the lethal doses of E.coli bacterial toxin, 's

> > Viper venom, palytoxin and adriamycin in almost all of the

animals

> > and other laboratory experimental models such as isolated hearts.

> >

> > Excited by these findings, I contacted a number of pharmaceutical

> > companies about carnitine's potential for the treatment of sepsis

> and

> > septic shock which is increasingly common in hospitals. I ran

into

> a

> > stone wall mainly because of the absence of a strong carnitine

> > patent. Our colleagues in the government expressed interest, but

> the

> > opportunity somehow fell through the cracks. It was probably due

to

> > the fact that, because of urgency of the Vietnam war, almost

> > everybody in those days was trying mightily to find therapies to

> > counter malaria infection and radiation damage. The bioterrorism

> > threat was not yet a significant national issue.

> >

> > I had no choice but to set aside this project, but Major Vick

> > continued to conduct other laboratory studies with carnitine with

> > exciting results.

> >

> > I then decided to pursue carnitine for the medical condition of

> > myocardial ischemia where the animal data continued to be highly

> > promising. After communicating with approximately thirty U.S. and

> > international pharmaceutical companies, I met Dr. Claudio

Cavazza,

> > the proprietor of the privately held, research-oriented Italian

> > pharmaceutical company, Sigma-tau S.p.A.

> >

> > Based on biochemical as well as pharmacological data, he became

> > convinced of carnitine's broad medical potential, and invested,

and

> > has continued to invest, substantial amounts of money in basic

and

> > clinical research including the development of related molecules

> such

> > as l-acetylcarnitine and proprionylcarnitine.

> >

> > Time passed and we paused different paths for awhile. When,

> however,

> > the anthrax scare burst on the national scene and the real

> > possibility that bioterrorism agents which cause septic shock

could

> > be used as weapons of mass destruction, I became somewhat

alarmed.

> I

> > then called Dr. Cavazza to discuss this situation and was very

> happy

> > with what I heard.

> >

> > In the past, some preliminary laboratory studies in septic shock

> with

> > l-acetylcarnitine were conducted with promising results. For

> example,

> > one study reported that l-acetylcarnitine could significantly

block

> > the lethal dose of the bacterial endotoxin substance, LPS.

> >

> > In addition, two preliminary clinical studies were done in

patients

> > with septic shock with encouraging results.

> >

> > In the first study, l-acetylcarnitine was administered

> intravenously

> > and found to improve the metabolism of body fuel substrates such

as

> > fatty acids and branched-chain amino acids. In septic shock

> patients,

> > the mitochondria, the energy producing parts of the cell, are

> > compromised. Also, there is an increase in blood coagulation,

which

> > reduces the blood supply to body tissues and, therefore, much

> needed

> > oxygen to the cells. This further compromises mitochondrial

> function

> > leading to a decrease in the cells'

> > metabolic capacity to generate fuel not only to maintain normal

> > functioning cells but also to keep them alive. Despite the

> seriously

> > compromised mitochondria and significant decreased in energy

> output,

> > l-acetylcarnitine managed to increase cellular production of

> energy.1

> >

> > A preliminary double-blind clinical study was conducted in

patients

> > with septic shock. Both during and after the infusion of l-

> > acetylcarnitine both systolic and diastolic blood pressure were

> > significantly elevated. Also, the clinical investigations

reported

> > and improvement in blood oxygenation.2

> >

> > Now let's switch gears to some interesting recent findings

> regarding

> > the central nervous system, l-acetylcarnitine and septic shock

> > patients.

> >

> > Because of promising scientific data, Dr. Cavazza decided to

> develop

> > acetyl-carnitine for medical conditions that involve the central

> > nervous system, or brain, as well as the peripheral nervous

system.

> > In addition to having the cardioprotective effects of carnitine,

l-

> > acetylcarnitine offers additional benefits by protecting nerve

> cells

> > when they are seriously challenged.

> >

> > Drs. Wesley Ely and other experts in shock management at the

> > Vanderbilt University Medical Center found that delirium, which

is

> > common in septic shock, is an indicator or prognosticator of

> certain

> > clinical outcomes or how well or poorly a patient does.3-4

> >

> > It is not commonly appreciated that septic shock patients who

> managed

> > to survive the life-threatening crisis have serious debilitating

> > clinical sequelae, including those involving the central nervous

> > system. They found that the degree of these debilitating central

> > nervous system effects were proportional to the severity and

> duration

> > of the delirium. Also, the more severe the delirium, the lower

the

> > survival rate and the duration in the hospital is significantly

> > longer.

> >

> > These data suggest that there is a real possibility that the

brain

> > may play a major role in septic shock.

> >

> > There are a number of laboratory studies that report that l-

> > acetylcarnitine is an active molecule in the brain. For example,

a

> > study was conducted in dogs to determine whether carnitine and l-

> > acetylcarnitine protected the dog brain after it was deprived of

> > oxygen by inducing cardiac arrest. It was found that l-

> > acetylcarnitine significantly reversed the neurologic deleterious

> > effects of oxygen deprival, while carnitine did not. The

> > investigators conclude that l-acetylcarnitine works by restoring

> the

> > brain's normal aerobic or oxygen-based metabolism, normalizing

the

> > production of ATP, or cell energy.5

> >

> > Similar brain protecting properties of l-acetylcaritine against

> > oxygen deprivation in rats has also been reported.

> >

> > The brain effects of l-acetylcarnitine have not yet been studied

in

> > septic shock animal models or patients. We do know, however, that

> it

> > crosses the blood-brain barrier in humans. It stimulates the

> > production of plasma cortisol and endorphins and increases

cerebral

> > blood flow to certain parts of the brain. It has also been

reported

> > to benefit patients with certain diseases of the nervous system.

> >

> > L-acetylcarnitine's combined cardiovascular and central nervous

> > system properties offer promise to septic shock patients. I have

> > consulted with a group of experts who, after evaluating all the

> > promising pieces of evidence, agreed that it is worthy of a

> clinical

> > trial in such patients.

> >

> > There are approximately 750,000 cases of severe sepsis a year,

with

> > about a thirty-three percent mortality rate. Septic shock now

kills

> > more patients per year than breast, colon, pancreatic and

prostate

> > cancers combined!

> >

> > It is important to note that bioterrorism toxic agents cause

septic

> > shock or damage the brain or do both. In my opinion, the

> possibility

> > that l-acetylcarnitine may counter some of these toxic effects

> should

> > be pursued either alone or in combination with other promising

> agents.

> >

> >

> > References:

> >

> > Gasparetto A., Corbucci G.G., DeBlasi R.A., Antonelli M.,

Baqiella

> > E., D'eddio S., Trevisani C.: Influence of acetyl-carnitine

> infusion

> > on haemodynamic parameters and survival of circulatory-shock

> > patients. INT.J. CLIN.

> > PHARM.RESX1(2)83-92 (1991)

> >

> > Nanni G., Pittiruti M., Giovannini I., Boldrini G., Ronconi P.,

> > Castagneto

> > M.: Plasma carnitine levels and urinary excretion during sepsis.

> > JPEN9: 483-490, 1985

> >

> > Ely, E.W., , J., Shinitani, G.S., May, L., Truman, B.,

> Dittus,

> > B., Gautam. S., Bernard, G., Speroff, T., Hart R. Long-term

> > neuropsychological deficits following delirium in mechanically

> > ventilated ICU patients. Am. J.

> > Respir. Crit. Care Med. 165(8):A30, 2002. (now in press at Crit

> Care

> > Medicine after peer review)

> >

> > Ely, E.W., Shintani, A., Bernanrd, G., ., J., Gordon, S.,

> May,

> > L., Truman, B., Gautam, S., Inouye, S., Dittus, B., Speroff, T.

> > Delirium in the ICU is associated with prolonged length of stay

in

> > the hospital and higher mortality. Am J. Respir. Crit Care Med.

165

> > (8):A23, 2002. (now under review at NEJM)

> >

> > Rosenthal, R.E., , R., Wells W., Fiskum, G., Post-

ischemic

> > administration of acetyl-l-carnitine (ALCAR) prevents

neurological

> > injury following prolonged cardiac arrest in dogs, Abstract No.

> DV9,

> > Pharm. Of Cerebral Ischemia '92, Marburg, Germany (1992).

> >

> >

> >

> >

> >

> > 1: Infection. 1993 Mar-Apr;21(2):83-8. Related Articles, Links

> >

> >

> >

> > Azithromycin versus doxycycline for treatment of erythema

> migrans:

> >

> > clinical and microbiological findings.

> >

> >

> >

> > Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V,

> Jereb

> > M.

> >

> >

> >

> > Department of Infectious Diseases, University Medical Center,

> > Ljubljana, Slovenia.

> >

> >

> >

> > The effectiveness of azithromycin and doxycycline in the

> > treatment of erythema migrans was compared in a prospective

> > randomized trial. One hundred seven adult patients with typical

> > erythema migrans, examined in the Lyme Borreliosis Outpatients'

> > Clinic, University Department of Infectious Diseases in

Ljubljana,

> > were included in the study. Fifty-five patients received

> azithromycin

> > (500 mg twice daily for the first day, followed by 500 mg once

> daily

> > for four days) and 52 patients received doxycycline (100 mg twice

> > daily for 14 days). The mean duration of skin lesions after the

> > beginning of treatment was 7.5 +/- 5.9 days (median value 5,

range

> 2-

> > 28

> >

> > days) in the azithromycin group and 11.4 +/- 7.8 days (median

value

> > 9, range

> >

> > 2 days--8 weeks) in the doxycycline group (p < 0.05). Borrelia

> > burgdorferi was isolated from erythema migrans in 28 patients

> before

> > therapy: in 13 out of 52 in the doxycycline group and in 15 out

of

> 55

> > in the azithromycin group. Three months after therapy, the

culture

> > was positive in four out of

> >

> > 13 patients treated with doxycycline and in one of the 15

patients

> > who received azithromycin. A biopsy was repeated in all the

> patients

> > with a positive isolation from the first skin specimen. During

the

> > first 12 months'

> >

> > follow-up, three patients treated with doxycycline but none in

the

> > azithromycin group developed major manifestations of Lyme

> > borreliosis, while

> >

> > 15 doxycycline recipients and 10 azithromycin recipients

developed

> > minor consecutive manifestations.

> >

> >

> >

> > Publication Types:

> >

> >

> >

> > * Clinical Trial

> >

> > * Randomized Controlled Trial

> >

> >

> >

> >

> >

> > PMID: 8387966 [PubMed - indexed for MEDLINE]

> >

>

[Guest guest]

a PAULA paullllaaaa,

I got your message loud and clear. I was just peeeved at the

carnitine factoid.. I just thought that if the medical

establishemnt, which is a trillion dollar business, thought carnitine

would be as GREAT as they claimed it would be, 'the miracle

supplement', that they would make huge bugggs out of it.

tony

> > >

> > > Azithromycin in Chronic Fatigue Syndrome (CFS)

> > > ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

> > > an analysis of clinical data

> > >

> > > Authors: Ruud CW Vermeulen and Hans R Scholte

> > >

> > > Journal of Translational Medicine 2006, 4:34

> > > doi:10.1186/1479-5876-4-34

> > >

> > > Published 15 August 2006

> > >

> > >

> > > Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of

> > > clinical data

> > >

> > > Ruud C.W. Vermeulen*1 and Hans R. Scholte2

> > > Address: 1CFS and Pain Research Center Amsterdam, Waalstraat 25-

> 31,

> > > 1078 BR Amsterdam, The Netherlands, 2Department of

Biochemistry,

> > > Erasmus MC-University Medical Center Rotterdam, Rotterdam, The

> > > Netherlands.

> > >

> > > E-mail: Ruud CW Vermeulen* - rv@;

> > > Hans R Scholte h.scholte@

> > > * Corresponding author

> > >

> > >

> > > Abstract

> > >

> > > Background: CFS is a clinical state with defined symptoms, but

> > > undefined cause. The patients may show a chronic state of

immune

> > > activation and treatment with an antibiotic in this subgroup

has

> > been

> > > suggested.

> > >

> > > Methods:

> > >

> > > In a retrospective study, the response of CFS patients to

> > > azithromycin, an antibiotic and immunomodulating drug, has been

> > > scored from the patients records and compared with clinical and

> > > laboratory data. Azithromycin was not the first choice therapy,

> but

> > > offered when the effect of counseling and L-carnitine was

> > considered

> > > insufficient by the patient and the clinician.

> > >

> > > Results:

> > >

> > > Of the 99 patients investigated, 58 reported a decrease in the

> > > symptoms by the use of azithromycin. These responding patients

> had

> > > lower levels of plasma acetylcarnitine.

> > >

> > > Conclusion:

> > >

> > > The efficacy of azithromycin in the responsive patients could

be

> > > explained by the modulating effect on a chronic primed state of

> the

> > > immune cells of the brain, or the activated peripheral immune

> > system.

> > > Their lower acetylcarnitine levels may reflect a decreased

> > > antioxidant defense and/or an increased consumption of

> > > acetylcarnitine caused by oxidative stress.

> > >

> > >

> > >

> > > Background

> > >

> > > In 1994 Fukuda et al. [1] defined CFS as a chronic persistent

> > fatigue

> > > that is present for over 6 months, is not caused by activity

nor

> > > alleviated by rest and accompanied with at least 4 other

> > > symptoms: cognitive impairment, pain in joints, muscles or

head,

> > > unrefreshing sleep, soar throat, tender lymph nodes and

> > > postexertional malaise with slow recovery. Nevertheless, CFS

> > remained

> > > subject to debate and even the mere existence of the syndrome

was

> > > still questioned by some. The presentation of the results of

> > > quantitative morphology of the brain in CFS patients by Okada

et

> al

> > > [2], later confirmed by De Lange et al [3] may change this

> opinion.

> > > The loss of grey matter in the brain, especially in Brodmanns

> area

> > > 9, was related to physical impairment, but not to the duration

of

> > the

> > > symptoms. Although other explanations were considered as well,

> this

> > > may indicate the occurrence of a major trauma to the brain at

the

> > > start of the disease. This could also explain the low recovery

> rate

> > > in adults, because repair in adult brain is limited [4].

> > >

> > >

> > > The severity of the sickness, both the symptoms and the lowered

> > > adaptation to physical stress, may fluctuate whenever

infections

> > and

> > > stress come and go. The Th1 to Th2 cytokine shift in CFS

patients

> > > will make them more vulnerable to infections [5] and it has

been

> > > suggested that they have more often chronic infections [6-8].

The

> > > predisposition for acquiring CFS may be genetically determined

> [9,

> > > 10], the occurrence is influenced by the severity of the

immune

> > > response [11]. The result is a chronic hyper-oxidative state of

> > > sickness [12, 13], in the brain itself [14] that cannot be

> stopped

> > > [15]. Preliminary evidence of a relation between post-

infectious

> > > fatigue and mitochondrial dysfunction indicates a complex

> response

> > > involving acetylcarnitine [16].

> > >

> > >

> > > The clinical presentation of the symptoms and chances for

> recovery

> > > will depend on the balance between the irreversible loss of

grey

> > > cells and activation of the immune system.

> > > According to De Meirleir et al, the presence of RNase-L and

> > elastase

> > > may offer an indication for this balance [17-19].

> > > Several treatment protocols to counteract the immune activation

> in

> > > CFS were presented [18, 20, 21], but the results were never

> > validated

> > > in a double blind study. Such proof is required as a rationale

> for

> > > treatment and provides a basis to understand the

pathophysiology

> of

> > > the disease. Comparing the outcome of clinical treatment

> protocols

> > > might add to our knowledge of CFS and its treatment until

double

> > > blind studies are available [22] .

> > >

> > >

> > > Azithromycin is an antibiotic with immunomodulatory effects [23-

> > 25].

> > > This antibiotic has been successfully used during periods of

six

> > > months of more in other chronic diseases [26-28].

> > > The side-effects are known for long term use and mainly limited

> to

> > > gastro-intestinal cramps. The chances for resistance limit its

> use

> > to

> > > individual patients under close supervision [28]. The drug is

> > > relatively inexpensive and extensive laboratory tests for side

> > > effects are not necessary. The result of a study in 10 CFS

> patients

> > > during 1 to 2 months was positive [26]. We studied the medical

> > > records of CFS patients for clinical and laboratory data

related

> to

> > > the outcome of the treatment with azithromycin.

> > >

> > >

> > >

> > >

http://www.fimdefelice.org/archives/arc.comment3_13_03bioter.html

> > >

> > >

> > >

> > >

> > >

> > > 411 North Avenue East, Cranford, New Jersey 07016-2436

Telephone

> > > (908) 272-2967 - Fax (908) 272-4589 www.fimdefelice.org

> > >

> > > March 13, 2003

> > >

> > >

> > > Bioterrorism: The Potential Role of L-Acetylcarnitine in the

> > > Treatment of Sepsis and Septic Shock

> > >

> > >

> > > L. DeFelice M.D.

> > >

> > > During the Vietnam war, Major Vick, a cardiovascular

> > > pharmacologist, and I conducted a series of laboratory studies

at

> > the

> > > Walter Army Institute of Research (WRAIR) which

demonstrated

> > > that carnitine dramatically prevented or reversed myocardial

> > > ischemia, a lack of oxygen to the heart.

> > >

> > > Following these studies, we decided to conduct other laboratory

> > > studies on whether carnitine could block lethal doses of

certain

> > > toxins. We evaluated primarily cardiovascular effects and

> survival.

> > > Some of these studies were conducted at other facilities.

> > >

> > > ly speaking, our hopes of success were not that high, but

we

> > > thought that, given carnitine's effect on protecting the heart

> > > against a lack of oxygen, it was worth a try. We also had read

> that

> > > other investigators had demonstrated that carnitine protects

> > against

> > > lethal doses of diphtheria toxin in animals.

> > >

> > > Then came the unexpected surprise. Carnitine, when given as

> > > treatment, after the toxicity process was in full swing,

reversed

> > the

> > > toxicity of the lethal doses of E.coli bacterial toxin,

's

> > > Viper venom, palytoxin and adriamycin in almost all of the

> animals

> > > and other laboratory experimental models such as isolated

hearts.

> > >

> > > Excited by these findings, I contacted a number of

pharmaceutical

> > > companies about carnitine's potential for the treatment of

sepsis

> > and

> > > septic shock which is increasingly common in hospitals. I ran

> into

> > a

> > > stone wall mainly because of the absence of a strong carnitine

> > > patent. Our colleagues in the government expressed interest,

but

> > the

> > > opportunity somehow fell through the cracks. It was probably

due

> to

> > > the fact that, because of urgency of the Vietnam war, almost

> > > everybody in those days was trying mightily to find therapies

to

> > > counter malaria infection and radiation damage. The

bioterrorism

> > > threat was not yet a significant national issue.

> > >

> > > I had no choice but to set aside this project, but Major Vick

> > > continued to conduct other laboratory studies with carnitine

with

> > > exciting results.

> > >

> > > I then decided to pursue carnitine for the medical condition of

> > > myocardial ischemia where the animal data continued to be

highly

> > > promising. After communicating with approximately thirty U.S.

and

> > > international pharmaceutical companies, I met Dr. Claudio

> Cavazza,

> > > the proprietor of the privately held, research-oriented Italian

> > > pharmaceutical company, Sigma-tau S.p.A.

> > >

> > > Based on biochemical as well as pharmacological data, he became

> > > convinced of carnitine's broad medical potential, and invested,

> and

> > > has continued to invest, substantial amounts of money in basic

> and

> > > clinical research including the development of related

molecules

> > such

> > > as l-acetylcarnitine and proprionylcarnitine.

> > >

> > > Time passed and we paused different paths for awhile. When,

> > however,

> > > the anthrax scare burst on the national scene and the real

> > > possibility that bioterrorism agents which cause septic shock

> could

> > > be used as weapons of mass destruction, I became somewhat

> alarmed.

> > I

> > > then called Dr. Cavazza to discuss this situation and was very

> > happy

> > > with what I heard.

> > >

> > > In the past, some preliminary laboratory studies in septic

shock

> > with

> > > l-acetylcarnitine were conducted with promising results. For

> > example,

> > > one study reported that l-acetylcarnitine could significantly

> block

> > > the lethal dose of the bacterial endotoxin substance, LPS.

> > >

> > > In addition, two preliminary clinical studies were done in

> patients

> > > with septic shock with encouraging results.

> > >

> > > In the first study, l-acetylcarnitine was administered

> > intravenously

> > > and found to improve the metabolism of body fuel substrates

such

> as

> > > fatty acids and branched-chain amino acids. In septic shock

> > patients,

> > > the mitochondria, the energy producing parts of the cell, are

> > > compromised. Also, there is an increase in blood coagulation,

> which

> > > reduces the blood supply to body tissues and, therefore, much

> > needed

> > > oxygen to the cells. This further compromises mitochondrial

> > function

> > > leading to a decrease in the cells'

> > > metabolic capacity to generate fuel not only to maintain normal

> > > functioning cells but also to keep them alive. Despite the

> > seriously

> > > compromised mitochondria and significant decreased in energy

> > output,

> > > l-acetylcarnitine managed to increase cellular production of

> > energy.1

> > >

> > > A preliminary double-blind clinical study was conducted in

> patients

> > > with septic shock. Both during and after the infusion of l-

> > > acetylcarnitine both systolic and diastolic blood pressure were

> > > significantly elevated. Also, the clinical investigations

> reported

> > > and improvement in blood oxygenation.2

> > >

> > > Now let's switch gears to some interesting recent findings

> > regarding

> > > the central nervous system, l-acetylcarnitine and septic shock

> > > patients.

> > >

> > > Because of promising scientific data, Dr. Cavazza decided to

> > develop

> > > acetyl-carnitine for medical conditions that involve the

central

> > > nervous system, or brain, as well as the peripheral nervous

> system.

> > > In addition to having the cardioprotective effects of

carnitine,

> l-

> > > acetylcarnitine offers additional benefits by protecting nerve

> > cells

> > > when they are seriously challenged.

> > >

> > > Drs. Wesley Ely and other experts in shock management at the

> > > Vanderbilt University Medical Center found that delirium, which

> is

> > > common in septic shock, is an indicator or prognosticator of

> > certain

> > > clinical outcomes or how well or poorly a patient does.3-4

> > >

> > > It is not commonly appreciated that septic shock patients who

> > managed

> > > to survive the life-threatening crisis have serious

debilitating

> > > clinical sequelae, including those involving the central

nervous

> > > system. They found that the degree of these debilitating

central

> > > nervous system effects were proportional to the severity and

> > duration

> > > of the delirium. Also, the more severe the delirium, the lower

> the

> > > survival rate and the duration in the hospital is significantly

> > > longer.

> > >

> > > These data suggest that there is a real possibility that the

> brain

> > > may play a major role in septic shock.

> > >

> > > There are a number of laboratory studies that report that l-

> > > acetylcarnitine is an active molecule in the brain. For

example,

> a

> > > study was conducted in dogs to determine whether carnitine and

l-

> > > acetylcarnitine protected the dog brain after it was deprived

of

> > > oxygen by inducing cardiac arrest. It was found that l-

> > > acetylcarnitine significantly reversed the neurologic

deleterious

> > > effects of oxygen deprival, while carnitine did not. The

> > > investigators conclude that l-acetylcarnitine works by

restoring

> > the

> > > brain's normal aerobic or oxygen-based metabolism, normalizing

> the

> > > production of ATP, or cell energy.5

> > >

> > > Similar brain protecting properties of l-acetylcaritine against

> > > oxygen deprivation in rats has also been reported.

> > >

> > > The brain effects of l-acetylcarnitine have not yet been

studied

> in

> > > septic shock animal models or patients. We do know, however,

that

> > it

> > > crosses the blood-brain barrier in humans. It stimulates the

> > > production of plasma cortisol and endorphins and increases

> cerebral

> > > blood flow to certain parts of the brain. It has also been

> reported

> > > to benefit patients with certain diseases of the nervous system.

> > >

> > > L-acetylcarnitine's combined cardiovascular and central nervous

> > > system properties offer promise to septic shock patients. I

have

> > > consulted with a group of experts who, after evaluating all the

> > > promising pieces of evidence, agreed that it is worthy of a

> > clinical

> > > trial in such patients.

> > >

> > > There are approximately 750,000 cases of severe sepsis a year,

> with

> > > about a thirty-three percent mortality rate. Septic shock now

> kills

> > > more patients per year than breast, colon, pancreatic and

> prostate

> > > cancers combined!

> > >

> > > It is important to note that bioterrorism toxic agents cause

> septic

> > > shock or damage the brain or do both. In my opinion, the

> > possibility

> > > that l-acetylcarnitine may counter some of these toxic effects

> > should

> > > be pursued either alone or in combination with other promising

> > agents.

> > >

> > >

> > > References:

> > >

> > > Gasparetto A., Corbucci G.G., DeBlasi R.A., Antonelli M.,

> Baqiella

> > > E., D'eddio S., Trevisani C.: Influence of acetyl-carnitine

> > infusion

> > > on haemodynamic parameters and survival of circulatory-shock

> > > patients. INT.J. CLIN.

> > > PHARM.RESX1(2)83-92 (1991)

> > >

> > > Nanni G., Pittiruti M., Giovannini I., Boldrini G., Ronconi P.,

> > > Castagneto

> > > M.: Plasma carnitine levels and urinary excretion during sepsis.

> > > JPEN9: 483-490, 1985

> > >

> > > Ely, E.W., , J., Shinitani, G.S., May, L., Truman, B.,

> > Dittus,

> > > B., Gautam. S., Bernard, G., Speroff, T., Hart R. Long-term

> > > neuropsychological deficits following delirium in mechanically

> > > ventilated ICU patients. Am. J.

> > > Respir. Crit. Care Med. 165(8):A30, 2002. (now in press at Crit

> > Care

> > > Medicine after peer review)

> > >

> > > Ely, E.W., Shintani, A., Bernanrd, G., ., J., Gordon,

S.,

> > May,

> > > L., Truman, B., Gautam, S., Inouye, S., Dittus, B., Speroff, T.

> > > Delirium in the ICU is associated with prolonged length of stay

> in

> > > the hospital and higher mortality. Am J. Respir. Crit Care Med.

> 165

> > > (8):A23, 2002. (now under review at NEJM)

> > >

> > > Rosenthal, R.E., , R., Wells W., Fiskum, G., Post-

> ischemic

> > > administration of acetyl-l-carnitine (ALCAR) prevents

> neurological

> > > injury following prolonged cardiac arrest in dogs, Abstract No.

> > DV9,

> > > Pharm. Of Cerebral Ischemia '92, Marburg, Germany (1992).

> > >

> > >

> > >

> > >

> > >

> > > 1: Infection. 1993 Mar-Apr;21(2):83-8. Related Articles,

Links

> > >

> > >

> > >

> > > Azithromycin versus doxycycline for treatment of erythema

> > migrans:

> > >

> > > clinical and microbiological findings.

> > >

> > >

> > >

> > > Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V,

> > Jereb

> > > M.

> > >

> > >

> > >

> > > Department of Infectious Diseases, University Medical

Center,

> > > Ljubljana, Slovenia.

> > >

> > >

> > >

> > > The effectiveness of azithromycin and doxycycline in the

> > > treatment of erythema migrans was compared in a prospective

> > > randomized trial. One hundred seven adult patients with typical

> > > erythema migrans, examined in the Lyme Borreliosis Outpatients'

> > > Clinic, University Department of Infectious Diseases in

> Ljubljana,

> > > were included in the study. Fifty-five patients received

> > azithromycin

> > > (500 mg twice daily for the first day, followed by 500 mg once

> > daily

> > > for four days) and 52 patients received doxycycline (100 mg

twice

> > > daily for 14 days). The mean duration of skin lesions after the

> > > beginning of treatment was 7.5 +/- 5.9 days (median value 5,

> range

> > 2-

> > > 28

> > >

> > > days) in the azithromycin group and 11.4 +/- 7.8 days (median

> value

> > > 9, range

> > >

> > > 2 days--8 weeks) in the doxycycline group (p < 0.05). Borrelia

> > > burgdorferi was isolated from erythema migrans in 28 patients

> > before

> > > therapy: in 13 out of 52 in the doxycycline group and in 15 out

> of

> > 55

> > > in the azithromycin group. Three months after therapy, the

> culture

> > > was positive in four out of

> > >

> > > 13 patients treated with doxycycline and in one of the 15

> patients

> > > who received azithromycin. A biopsy was repeated in all the

> > patients

> > > with a positive isolation from the first skin specimen. During

> the

> > > first 12 months'

> > >

> > > follow-up, three patients treated with doxycycline but none in

> the

> > > azithromycin group developed major manifestations of Lyme

> > > borreliosis, while

> > >

> > > 15 doxycycline recipients and 10 azithromycin recipients

> developed

> > > minor consecutive manifestations.

> > >

> > >

> > >

> > > Publication Types:

> > >

> > >

> > >

> > > * Clinical Trial

> > >

> > > * Randomized Controlled Trial

> > >

> > >

> > >

> > >

> > >

> > > PMID: 8387966 [PubMed - indexed for MEDLINE]

> > >

> >

>

[Guest guest]

This is probably my fault. I did get your main point of course, but I

picked up on the carnitine part anyway because I was interested in it.

- Kate

On Aug 19, 2006, at 3:30 PM, pjeanneus wrote:

> Tony,Tony,Tony, you missed my point. I was pushing Zithromax, as

> usual, and trying to demonstrate that it was probably killing

> bacteria in the brain, not just somehow raising carnitine levels.

> Hey, you know I am not a supplement pusher.

>

> a

>