Fwd: Alternative AIDS Therapy from Cheap Generics

[Guest guest]

(I am posting this to show the difference between hype, spin and reality

concerning drugs purported to be newer, better, more effective by big pharma. I

am not posting this to promote these oother drugs listed. If you take drugs, it

is your responsibility to really understand what they really are, what they do

and what damage they will/may cause.

 

Frank)

 

 

2 Apr 2004 17:31:00 -0000

Alternative AIDS Therapy from Cheap Generics

press-release

 

 

The Institute of Science in Society Science Society

Sustainability http://www.i-sis.org.uk

 

General Enquiries sam Website/Mailing List

press-release ISIS Director m.w.ho

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

 

Alternative AIDS Therapy from Cheap Generics

 

*************************************

 

 

Conventional combination treatments for HIV/AIDS cost $22

000 per patient per year in the US. Do cheaper and less

toxic drugs exist? Sam Burcher and Dr Mae-Wan Ho report

 

 

A fully referenced version of this report is posted on ISIS

member's website.

www.i-sis.org.uk/AlternativeAids.php

www.i-sis.org.uk/membership.php

 

 

A quintet of older drugs could make a cheap and safe alternative to current

anti-HIV

drug cocktails, claim Drs Aldar Bourinbaiar and Vichai

Jirathitikal of Immunitor Corporation in Thailand, which

created the V1 AIDS vaccine (see “Pink Panacea, an AIDS

vaccine?” this series).

 

 

In a paper published in Current Pharmaceutical Design in

2003, the two scientists review evidence suggesting that

these old, widely available conventional drugs may have

anti-retroviral and immune modulating properties, which

could help recover the immune system of HIV/AIDS patients.

 

Warfarin

 

*******

 

Warfarin is a synthetic drug derived from the naturally

occurring coumarins found in a wide variety of plants

species worldwide. Coumarins are the parent organic

compounds that work as natural pesticides in plants such as

lavender, grasses like sweet clover and food plants like

strawberries and lemons. In 1868, courmarins were

synthesised in the laboratory to make perfumes and

flavouring. When combined with glucose they produce

glycosides, which are anti-cancer, anti-fungus and anti-

coagulant. All structurally related courmarins show potent

anti-HIV activity. The use of coumarins as an immune support

accompanying standard chemotherapy treatment has

significantly improved survival rates of colon cancer

patients. More recently, warfarin is used as an anti-

coagulating drug in the treatment of heart disease and

stroke.

 

 

There is some anecdotal evidence suggesting that a small

daily dose of 2mg of warfarin do not affect the

“prothrombin-time”, a lab test to monitor blood coagulation

in HIV patients, but does significantly lower viral loads.

 

 

Warfarin possesses four essential properties for fighting

HIV: inhibition of serine protease, aspartyl protease,

reverse transcriptase and integrase, all of which are

central to the virus’s ability to replicate.

 

 

An average PI (protease inhibitor) used in triple-drug

treatments of HIV cost between $10-$20 per day, in contrast

to a daily dose of 2 mg warfarin which costs as little as 10

cents.

 

 

Reverse transcriptase (RT) inhibitors are also essential in

the successful treatment of HIV/AIDS. By far the most

prescribed RT is AZT, which has side effects in up 75% of

patients with HIV/AIDS.

 

 

Warfarin is of further value in the treatment of cognitive

functions in HIV/AIDS patients. A daily dose of warfarin

appears to improve the fluency of speech and mental aptitude

of patients suffering from progressive dementia associated

with the full-blown AIDS disease.

 

 

Bourinbair and Jirathitikal found that a combination of

warfarin with anti-HIV compounds discovered by them, such as

cimetidine and lavamisole seem to enhance the beneficial

immune effect.

 

Cimetidine

 

********

 

Cimetidine is an over the counter ant-acid or anti-ulcer

drug otherwise known as Tagamet, and as such inhibits

gastric acid secretion via histamine type (H2) receptors on

parietal cells (in the stomach.) Cimetidine was developed as

part of a research effort led by Nobel laureate Sir James

Black, and was the first H2-antagonist to receive approval

from the FDA (Food and Drug Administration) in 1977. On

account of its excellent safety record, it is now widely

available as an over the counter drug.

 

 

Cimetidine first came to the attention of Bourinbaiar and

Jirathitikal when they observed the inhibition of human T

cells leukaemia virus (HTLV-1) secretion from chronically

infected cells. This led them to the idea that viral release

is regulated in the same way as gastric acid secretion, and

to discover that cimetidine has broad anti-retroviral

activity.

 

 

Further studies revealed that cimeditine, unlike AZT, which

was used as a control, produced no cytotoxicity even at the

highest dose tested (1mM). According to the authors, this is

an exceptional drug index that cannot be matched by any

drugs currently used in the treatment of HIV/AIDS. Twice

daily doses of 200mg of cimetidine will suffice to provide

steady IC50 levels (concentration producing 50% inhibition)

for HIV replication.

 

 

It appears that the success of H2 antagonists tested for

anti-viral activity depends on the imidazole nucleus. Some,

though not all non-nucleoside reverse transcriptase

inhibitors (NNRTIs) possess imidazole rings. It is thus

likely that cimetidine acts like an NNRTI and has the

ability to treat HIV infection.

 

 

NNRTIs have a reputation for rapidly eliciting resistance

due to mutations of the amino acids surrounding the NNRTIs’

binding site. So emerging strains of resistant HIV can be

confronted if the NNRTIs are combined with other anti-HIV

agents.

 

 

The combination of warfarin and cimeditine was previously

thought to be incompatible, but there have been no reports

of adverse reactions at low doses of cimetidine and 2mg of

warfarin in more than a hundred available references in the

TOXLINE database. In fact, the cases of anaemia caused by

cimetidine is 2.3 per 100 000 as opposed to 70% in patients

treated with AZT.

 

 

In trials, cimeditine significantly enhanced a variety of

immune functions both in vivo and in vitro and was

successful in partially restoring the immune function in 33

AIDS patients.

 

 

Cimeditine sells over the counter for 20 cents per 400mg

pill, while in China bulk buying the pills may cost as

little as $18 per kilo.

 

 

Levamisole

 

*********

 

Levamisole was synthesised in the early 1960s and used

primarily for the treatment of intestinal worms in animals.

In the 1990s, Levamisole was approved for human medicinal

use to provide immune support for colon cancer patients.

Bourinbair and colleagues, aware that it contained the same

imidazole ring as cimeditine surmised that it might also

have anti-HIV activity. They found that the IC50 of

Levamisole to be around 0.1mM, and there was no toxicity at

the highest dose of 1mM. The drug was effective against

several lab strains and primary isolates of HIV-1.

 

 

However, chronic daily doses of Levamisole appeared to have

an accumulated toxic effect, usually severe nausea and

granulocytopenia (a reduction of granulocytes, a kind of

white blood cells in the blood). In general, once weekly low

doses of the drug are well tolerated.

 

 

Interestingly, levamisole can either enhance or suppress the

immune system depending on the administered dose. Many

studies have found beneficial effects of levamisole in

various immune deficiency disorders. Similarly, the drug

used alone, or in combination with interferon and other

anti-inflammatory drugs significantly improves the healing

of eye and skin lesions caused by herpes simplex and zoster

virus. Levamisole is also strikingly effective against auto-

immune diseases such as rheumatoid arthritis and systemic

lupus erythematosus.

 

 

Other studies, however, have found no benefit from

levamisole.

 

 

Since 1985, Levamisole has undergone sporadic tests with

AIDS patients with conflicting results. Some trials report

no effect, while others found beneficial effects.

 

 

Bourinbair and Jirathitikal conclude that levamisole may

have both immune modulating and antiviral activities. But

caution must be exercised in using this drug because “the

dosage, administration schedule, gender and many other

variables seem to have a serious influence on the outcome of

the therapy.”

 

 

For human use, it cost $6 per pill, but the same pill for

animal use costs just 6 cents. So the cost for treating a

sheep for one year is $1, but treating a human for one year

would cost $1,200.

 

Acetaminophen

 

************

 

Acetaminophen was first synthesised in 1878 as an

intermediary compound in the manufacture of synthetic

aniline dyes. Some fifteen years later, its analgesic or

pain- killing property was identified. But its clinical

application did not come until 1949 when a study by Nobel

laureates Brodie and Axelrod was published, and by the

1960s, it was made available as an over the counter drug.

Brand names ascribed to acetaminophen are Paracetamol,

Panadol, and Tylenol etc, as a non-toxic broad-spectrum pain

reliever with few or no side effects at therapeutic doses.

It is thought to cause fewer side effects than aspirin, a

non-common non-steroidal, anti-inflammatory (NSAID) drug.

 

 

It is not fully understood how acetaminophen works, but it

is believed to inhibit prostaglandin synthesis or the

actions of chemical mediators or other substances that

sensitise the pain receptors to mechanical or chemical

stimulation. During a study by Bourinbair & Jirantikal to

identify a serine protease for use in contraceptive creams,

they discovered that acetaminophen displayed significant

anti-HIV activity while it was used as a negative control.

The anti-viral effect was specific and almost 100%

inhibition was observed at 1mM (150mg/ml), while IC50 was

20mg/ml, which is satisfied by the standard dosage of a

650mg pill every six hours.

 

 

Studies of acetaminophen have shown it to be non-toxic even

in the highest dose of 1mM tested, and it has been used to

counteract toxicity in AIDS patients treated with AZT. No

further toxicity occurred in these patients, but the anti-

HIV activity in acetaminophen was not studied in these

cases.

 

 

It is not yet clear how acetaminophen affects HIV

replication, but it its thought to behave in a similar way

to reverse transcriptase inhibitors (RT) that inhibit the

synthesis of DNA from RNA.

 

 

As far as cost is concerned, these familiar painkillers may

well turn out to be the cheapest of all currently available

reverse transcriptase (RT) drugs.

 

Gramicidin

 

*********

 

Gramicidin D was the first ever clinically identified

antibiotic predating penicillin by one year. It was isolated

from the soil bacterium Bacillis brevis by Rene Dubois,

hence “D”, in 1939. Gramicidins are short peptides of 15

alternating L- and D- amino acids that are synthesized

outside the genetic coding route. The D-amino acids are

unnatural in that they do not occur in proteins encoded in

the genome of organisms. There are several kinds of

gramicidins, differing in the amino acid sequence. They

usually exist as molecular complexes of two peptides. These

linear gramicidins are related to the cyclic (ring-shaped)

gramicidin S discovered later in the former Soviet Union.

 

 

Gramicidin acts by causing potassium to flow out from the

target cell, thus killing it. And because of its unique

construction it has never been implicated in the emergence

of resistant bacteria like so many younger antibiotics.

 

 

It was first used in the USA for the treatment of gram-

positive infections and was also widely used in over the

counter throat lozenges, dentifrices and mouthwashes.

Nowadays, it is available by prescriptions only as a

treatment for skin and eye infections. In Russia Gramicidin

S is available over the counter as a prophylactic

spermicide, which can be used in combination with condoms

and diaphragms. It can be applied topically as an anti-

microbial to treat skin infections caused by other viral or

fungal sexually transmitted diseases and also burns.

 

 

Gramicidin has been in clinical use for over 60 years and it

is non-toxic when administered topically or orally. However,

some medical opinions suggest toxicity in systemic use. This

may have been because gramicidin was used in combination

with other drugs, which caused side effects. More recent

studies have shown that systemic doses of gramicidin are

well tolerated and efficacious in the treatment of

experimental malaria in mice. Gramicidin injections cleared

the malaria parasite in mice in four days. It is hoped that

gramicidin can be a potent treatment for both AIDS and

malaria particularly in Africa where both diseases are

endemic.

 

 

Due to the presence of unnatural D-amino acids, gramicidin

has a remarkable resistance to peptide cleaving proteases

found in the body, such as blood, pus, urine and saliva. It

has a broad PH range (acid to alkaline) and remains active

for ten years at room temperature.

 

 

Bourinbaiar and Jirathitikal have shown that gramicidin is

highly effective against HIV and herpes simplex viruses at

non-toxic nanogram doses. The IC50 of gramicidin against 3

herpes simplex isolates was 0.3mg/ml. At an even lower dose

of 10ng/ml, it was active against both lab strains of HIV

and clinical isolates. When gramicidin was compared with the

most popular anti-HIV spermicide “N9”, it was found to be

1000 times more effective. “N9” could only display anti-

viral activity in doses that were toxic to cells. Despite

N9’s equivalence to household bleach, a toxic substance not

normally topically applied to skin, it continues to be

evaluated as a spermicide in clinical trials.

 

 

Thus, gramicidin may be a safe and more efficient

microbicide and spermicide than N9. Its use as a vaginal

suppository would make an extremely cheap and efficient

prophylactic or “barrier method” against HIV and other STDs.

A supply of 3kg would be sufficient for one year’s use, and

the cost is negligible. Gramicidin D already has US FDA

(Food and Drug Administration) approval for topical use, and

cyclic gramicidin S has been used in Russia as a spermicidal

preparation.

 

 

Gramicidin possesses a formidable list of attractive

properties, all of which are relevant against emerging

diseases. It is anti-STD, anti-fungal, anti-protozoan

(malaria) and is poorly absorbed by the skin, reducing the

risk of irritation. It enhances skin tissue healing and

resists and inhibits proteolytic enzymes, which break down

proteins in the body.

 

 

This 60 year-old drug has now come of age and its anti-viral

properties need to be confirmed in clinical trials.

 

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