Pain/Brain/Modulators

[Guest guest]

Since I used Ibuprofen (and my drug choices) becuase of addirional

mechanism besides antibacterial... here's a few more abstracts

Good description of microglia in the first one.

>

> all interesting abstracts on Mino at this addy:

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?SUBMIT=y

>

> all interesting abstracts on ibuprofen at this addy

> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?SUBMIT=y

>

> Arch Pharm Res. 2004 Mar;27(3):314-8. Related Articles, Links

>

>

> Inhibitory action of minocycline on lipopolysaccharide-induced

> release of nitric oxide and prostaglandin E2 in BV2 microglial

cells.

>

> Kim SS, Kong PJ, Kim BS, Sheen DH, Nam SY, Chun W.

>

> Department of Pharmacology, College of Medicine, Kangwon National

> University, Chunchon 200-701, Korea.

>

> Microglia are the major inflammatory cells in the central nervous

> system and become activated in response to brain injuries such as

> ischemia, trauma, and neurodegenerative diseases including

> Alzheimer's disease (AD). Moreover, activated microglia are known

to

> release a variety of proinflammatory cytokines and oxidants such

as

> nitric oxide (NO). Minocycline is a semisynthetic second-

generation

> tetracycline that exerts anti-inflammatory effects that are

> completely distinct form its antimicrobial action. In this study,

the

> inhibitory effects of minocycline on NO and prostaglandin E2

(PGE2)

> release was examined in lipopolysaccharides (LPS)-challenged BV2

> murine microglial cells. Further, effects of minocycline on

inducible

> nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)

expression

> levels were also determined. The results showed that minocycline

> significantly inhibited NO and PGE2 production and iNOS and COX-2

> expression in BV2 microglial cells. These findings suggest that

> minocycline should be evaluated as potential therapeutic agent for

> various pathological conditions due to the excessive activation of

> microglia.

>

> PMID: 15089037 [PubMed - indexed for MEDLINE

__________________________________________________________________

>

>

> : Neurobiol Dis. 2004 Jun;16(1):190-201. Related Articles, Links

>

>

> Minocycline reduces the lipopolysaccharide-induced inflammatory

> reaction, peroxynitrite-mediated nitration of proteins, disruption

of

> the blood-brain barrier, and damage in the nigral dopaminergic

system.

>

> Tomas-Camardiel M, Rite I, Herrera AJ, de Pablos RM, Cano J,

Machado

> A, Venero JL.

>

> Departamento de Bioquimica, Bromatologia, Toxicologia y Medicina

> Legal Facultad de Farmacia, Universidad de Sevilla, E-41012-

Seville,

> Spain.

>

> We have evaluated the potential neuroprotectant activity of

> minocycline in an animal model of Parkinson's disease induced by

> intranigral injection of lipopolysaccharide. Minocycline treatment

> was very effective in protecting number of nigral dopaminergic

> neurons and loss of reactive astrocytes at 7 days postlesion.

> Evaluation of microglia revealed that minocycline treatment highly

> prevented the lipopolysaccharide-induced activation of reactive

> microglia as visualized by OX-42 and OX-6 immunohistochemistry.

Short-

> term RT-PCR analysis demonstrated that minocycline partially

> prevented the lipopolysaccharide-induced increases of mRNA levels

for

> interleukin-1alpha and tumor necrosis factor-alpha. In addition,

> lipopolysaccharide highly induced protein nitration as seen by 3-

> nitrotyrosine immunoreactivity in the ventral mesencephalon.

> Minocycline treatment strongly diminished the extent of 3-

> nitrotyrosine immunoreactivity. We also found a direct correlation

> between location of IgG immunoreactivity-a marker of blood-brain

> barrier disruption-and neurodegenerative processes including death

of

> nigral dopaminergic cells and reactive astrocytes. There was also

a

> precise spatial correlation between disruption of blood-brain

barrier

> and 3-nitrotyrosine immunoreactivity. We discuss potential

> involvement of lipopolysaccharide-induced formation of

peroxynitrites

> and cytokines in the pathological events in substantia nigra in

> response to inflammation. If inflammation is proved to be involved

in

> the ethiopathology of Parkinson's disease, our data support the

use

> of minocycline in parkinsonian patients.

>

> PMID: 15207276 [PubMed - indexed for MEDLINE]

>

>

>

> ____________________________________________________________

> J Neurovirol. 2004 Oct;10(5):284-92. Related Articles, Links

>

>

> A novel action of minocycline: inhibition of human

immunodeficiency

> virus type 1 infection in microglia.

>

> Si Q, Cosenza M, Kim MO, Zhao ML, Brownlee M, Goldstein H, Lee S.

>

> Department of Pathology, Albert Einstein College of Medicine,

Bronx,

> New York 10461, USA.

>

> Human immunodeficiency virus type 1 (HIV-1) infection of the brain

> produces a characteristic disease called acquired immunodeficiency

> syndrome (AIDS) dementia in which productive infection and

> inflammatory activation of microglia and macrophages play a

central

> role. In this report, the authors demonstrate that minocycline

(MC),

> a second-generation tetracycline with proven safety and

penetration

> to the central nervous system, potently inhibited viral production

> from microglia. Inhibition of viral release was sustained through

the

> entire course of infection and even when the drug exposure was

> limited to the first day of infection.

>

> Minocycline was effective even at low viral doses, and against R5-

> and X4R5-HIV, as well as in single-cycle reporter virus assays.

>

> Electrophoretic mobility shift analysis showed that minocycline

> inhibited nuclear factor (NF)-kappaB activation in microglia.

>

> HIV-1 long terminal repeat (LTR)-promoter activity in U38 cells

was

> also inhibited. These results, combined with recently demonstrated

in

> vivo anti-inflammatory effects of MC on microglia, suggest a

> potential utility for MC as an effective adjunct therapy for AIDS

> dementia.

>

> PMID: 15385251 [PubMed - in process]