Low Dose Mino

[Guest guest]

Jelly:

Here are some abstracts relating to low dose Mino.

low dose in these cases are 20 mg and above.

Do you know of anyone (inculding Marshall) that has cut down

Mino to <5mg. and had that sample analysed?

Barb

Gan To Kagaku Ryoho. 2005 Mar;32(3):345-9.

[intrathoracic infusion with a combination of low-dose minocycline,

OK-432 and cisplatin for malignant pleural effusion]

Ishimori S, Okada S, Yamagata S, Satoh S.

Dept. of Thoracic Medicine, Kamaishi Municipal Hospital.

We investigated the effectiveness and complications of intrathoracic

infusion with a combination of cisplatin, OK-432, and minocycline for

malignant pleural effusion. All patients were hospitalized with chest

tube drainage of pleural effusion until the daily drainage volume was

less than 100 ml.

Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of

cisplatin were instilled into the pleural space. The administration

was repeated until drainage effusion disappeared. Therapeutic effect

was evaluated according to the following criteria: (1) excellent, no

fluid reaccumulation for at least 4 weeks as determined by chest

radiogram and clinical evaluation; (2) effective, fluid

reaccumulation less than 50% of original effusion with no need of

thoracentesis for symptomatic relief within 4 weeks after treatment;

and (3) failure, reaccumulation of more than 50% of the original

effusion requiring thoracentesis to relieve symptoms within 4 weeks

of treatment. Twelve patients with malignant effusion received the

combination treatment; 11 patients had primary lung cancer and one

had metastatic lung tumor from cancer of the rectum. In all cases,

the histology or cytology revealed adenocarcinoma. Eleven of the 12

patients had an excellent response with relief of clinical symptoms.

The remaining case failed to show any improvement. Complications such

as local pain, fever, nausea, and vomiting were mild and transient.

We conclude that combination administration of low-dose minocycline,

OK-432, and cisplatin into the thoracic cavity for malignant effusion

is an effective alternative treatment with the potential for

improvement of the general condition and reduced morbidity.

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Pain. 2005 May;115(1-2):71-83.

Minocycline attenuates mechanical allodynia and proinflammatory

cytokine expression in rat models of pain facilitation.

Ledeboer A, Sloane EM, Milligan ED, MG, Mahony JH, Maier SF,

Watkins LR.

Department of Psychology and the Center for Neuroscience, University

of Colorado at Boulder, Campus Box 345, Boulder, CO 80309-0345, USA.

Activated glial cells (microglia and astroglia) in the spinal cord

play a major role in mediating enhanced pain states by releasing

proinflammatory cytokines and other substances thought to facilitate

pain transmission. In the present study, we report that intrathecal

administration of minocycline, a selective inhibitor of microglial

cell activation, inhibits low threshold mechanical allodynia, as

measured by the von Frey test, in two models of pain facilitation. In

a rat model of neuropathic pain induced by sciatic nerve inflammation

(sciatic inflammatory neuropathy, SIN), minocycline delayed the

induction of allodynia in both acute and persistent paradigms.

Moreover, minocycline was able to attenuate established SIN-induced

allodynia 1 day, but not 1 week later, suggesting a limited role of

microglial activation in more perseverative pain states. Our data are

consistent with a crucial role for microglial cells in initiating,

rather than maintaining, enhanced pain responses. In a model of

spinal immune activation by intrathecal HIV-1 gp120, we show that the

anti-allodynic effects of minocycline are associated with decreased

microglial activation, attenuated mRNA expression of interleukin-

1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-1beta-

converting enzyme, TNF-alpha-converting enzyme, IL-1 receptor

antagonist and IL-10 in lumbar dorsal spinal cord, and reduced IL-

1beta and TNF-alpha levels in the CSF. In contrast, no significant

effects of minocycline were observed on gp120-induced IL-6 and

cyclooxygenase-2 expression in spinal cord or CSF IL-6 levels. Taken

together these data highlight the importance of microglial activation

in the development of exaggerated pain states.

PMID: 15836971 [PubMed - indexed for MEDLINE]

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Cereb Blood Flow Metab. 2006 Jan 4

Dose-response effect of tetracyclines on cerebral matrix

metalloproteinase-9 after vascular endothelial growth factor

hyperstimulation.

Lee CZ, Yao JS, Huang Y, Zhai W, Liu W, Guglielmo BJ, Lin E, Yang GY,

Young WL.

[1] 1Department of Anesthesia and Perioperative Care, University of

California, San Francisco, California, USA [2] 2Center for

Cerebrovascular Research, University of California, San Francisco,

California, USA.

Brain arteriovenous malformations (BAVMs) are a potentially life-

threatening disorder. Matrix metalloproteinase (MMP)-9 activity was

greatly increased in BAVM tissue specimens. Doxycycline was shown to

decrease cerebral MMP-9 activities and angiogenesis induced by

vascular endothelial growth factor (VEGF). In the present study, we

determined the dose-response effects of doxycycline and minocycline

on cerebral MMP-9 using our mouse model with VEGF focal

hyperstimulation delivered with adenoviral vector (AdVEGF) in the

brain. Mice were treated with doxycycline or minocycline,

respectively, at 1, 5, 10, 30, 50, or 100 mg/kg/day through drinking

water for 1 week. Our results have shown that MMP-9 messenger

ribonucleic acid (mRNA) expression was inhibited by doxycycline

starting at 10 mg/kg/day (P<0.02). Minocycline showed more potent

inhibition on MMP-9 mRNA expression, starting at 1 (P<0.005) and

further at more than 30 (P<0.001) mg/kg/day. At the enzymatic

activity level, doxycycline started to suppress MMP-9 activity at 5

mg/kg/day (P<0.001), while minocycline had an effect at a lower dose,

1 mg/kg/day (P<0.02). The inhibition of cerebral MMP-9 mRNA and

activity were highly correlated with drug levels in the brain tissue.

We also assessed the potential relevant signaling pathway in vitro to

elucidate the mechanisms underlying the MMP-9 inhibition by

tetracyclines. In vitro, minocycline, but not doxycycline, inhibits

MMP-9, at least in part, via the extracellular signaling-related

kinase 1/2 (ERK1/2)-mediated pathway.

This study provided the evidence that the tetracyclines inhibit

stimulated cerebral MMP-9 at multiple levels and are effective at

very low doses, offering great potential for therapeutic use.Journal

of Cerebral Blood Flow & Metabolism advance online publication, 4

January 2006; doi:10.1038/sj.jcbfm.9600268.