Minocycline, Jelly, 4 mg and minocycline

[Guest guest]

This

is a curious article for a couple of reasons. One is that HIV is probably not

the cause of sickness in AIDS but the facilitator. Mycoplasma and other opportunistic

bacteria are probably what really make the patient die. Thus the reason why

minocycline works.

But what

is really curious is that these little guys were given 4 mg/kg of minocycline.

I know, I know, they were just little monkeys. If they weighed about 25 lbs.

that would be about 40 mg of minocycline a day – not a very high dose.

Another

thing that has crossed my mind – watch out – what if Jelly’s

minocycline pill was a coated time release version and she is cutting it up?

Would she be getting a higher dose than she thinks all at once?

Jelly,

there are some good studies other than MP showing that pulsing minocycline may

be effective. There is an ideal point at which bacteria get zapped, and it may

not be the highest body concentration. One study suggests that as the concentration

lowers the bacteria, far from mutating, come back out to play, only to find

that the antibiotic is still there and still able to kill them. Do not assume

that any of us on this list know all there is to know. Hey, if you are getting

better and feel like you are herxing STICK WITH IT.

a Carnes

http://jama.ama-assn.org/cgi/content/abstract/293/16/2003

Neuroprotective

and Anti–Human Immunodeficiency Virus Activity of Minocycline

M. Zink, DVM, PhD; Uhrlaub, BS; DeWitt,

BS; Tauni Voelker, BS; Bullock, MS; ph Mankowski, DVM, PhD;

Tarwater, PhD; Janice Clements, PhD; Sheila Barber, PhD

JAMA. 2005;293:2003-2011.

Context The prevalence of human immunodeficiency virus (HIV)

central nervous system (CNS) disease has not decreased despite

highly active antiretroviral therapy. Current antiretroviral drugs

are expensive, have significant adverse effects including neurotoxicity,

and few cross the blood-brain barrier.

Objective To examine the ability of minocycline, an antibiotic with

potent anti-inflammatory and neuroprotective properties, to protect

against encephalitis and neurodegeneration using a rapid, high viral

load simian immunodeficiency virus (SIV) model of HIV-associated CNS

disease that constitutes a rigorous in vivo test for potential

therapeutics.

Design and Subjects Five SIV-infected pigtailed macaques were treated with

4 mg/kg per day of minocycline beginning at early asymptomatic

infection (21 days after inoculation). Another 6 macaques were

inoculated with SIV but remained untreated. Blood and cerebrospinal

fluid (CSF) samples were taken on days 7, 10, 14, 21, 28, 35, 43,

56, 70, 77, and 84, and all macaques were humanely killed at 84 days

after inoculation, a time that corresponds to late-stage infection

in HIV-infected individuals.

Main Outcome Measures Blood and CSF samples were tested for viral load by

real-time reverse transcription–polymerase chain reaction and

levels of monocyte chemoattractant protein 1 were quantitated by

enzyme-linked immunosorbent assay. The presence and severity of

encephalitis was determined by microscopic examination of tissues.

Central nervous system inflammation was further assessed by

measuring infiltration and activation of macrophages, activation of

p38 mitogen-activated protein kinase and expression of amyloid

precursor protein by quantitative immunohistochemistry.

Results Minocycline-treated macaques had less severe encephalitis (P = .02), reduced CNS expression

of neuroinflammatory markers (major histocompatibility complex class

II, P = .03; macrophage

marker CD68 , P = .07;

T-cell intracytoplasmic antigen 1, P = .03;

CSF monocyte chemoattractant protein 1, P = .001), reduced activation of p38

mitogen-activated protein kinase (P<.001),

less axonal degeneration (-amyloid precursor

protein, P = .03), and

lower CNS virus replication (viral RNA, P = .04; viral antigen, P = .04). In in vitro analysis,

minocycline suppression of HIV and SIV replication in cultured primary

macrophages did not correlate with suppression of activation of

p38-mitogen-activated protein kinase pathways, whereas suppression

in primary lymphocytes correlated with suppression of p38

activation.

Conclusions In this experimental SIV model of HIV CNS disease,

minocycline reduced the severity of encephalitis, suppressed viral

load in the brain, and decreased the expression of CNS inflammatory

markers. In vitro, minocycline inhibited SIV and HIV replication.

These findings suggest that minocycline, a safe, inexpensive, and

readily available antibiotic should be investigated as an anti-HIV

therapeutic.