Lähettäjä: Soijuv Lähetetty: 5.5.2005 8:32
Seuraavan tutkimuksen mukaan antibioottihoito (Minosykliini) esti esim. HIV-virusten lisääntymisen ja laski tulehdusarvoja keskushermostossa. Yleisesti sanotaan että antibiooteista ei ole hyötyä virusten aiheuttamissa taudeissa - asiaa lienee syytä tarkastella uudelleen. Minosykliinihoitoa käytetään jonkin verran borrelioosin hoidossa eri maissa. Sen ajatellaan olevan tehokas keskushermostotulehdusten hoidossa.
http://jama.ama-assn.org/cgi/content/ab ... 93/16/2003
Neuroprotective and Anti?Human Immunodeficiency Virus Activity of Minocycline
M. Christine Zink, DVM, PhD; Jennifer Uhrlaub, BS; Jesse DeWitt, BS; Tauni Voelker, BS; Brandon Bullock, MS; Joseph Mankowski, DVM, PhD; Patrick 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 ({beta}-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.
ANTIBIOOTTEJA VIRUSTEN HOITOON
Valvojat: Jatta1001, Borrelioosiyhdistys, Bb
ANTIBIOOTTEJA VIRUSTEN HOITOON
Viimeksi muokannut Bb, Su Maalis 08, 2009 18:55. Yhteensä muokattu 1 kertaa.
Lähettäjä: Soijuv Lähetetty: 13.5.2005 13:10
Lisää minosykliinin käytöstä keskushermostoperäisissä virustaudeissa:
http://www.sciencedirect.com/science?_o ... 7%23579292!
Minocycline delays disease onset and mortality in reovirus encephalitis
Sarah M. Richardson-Burns and Kenneth L. Tyler
aNeuroscience Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA
bDepartments of Neurology, Medicine, Immunology, and Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
cDenver Veteran's Affairs Medical Center, Denver, CO 80220, USA
Received 7 September 2004; revised 2 November 2004; accepted 9 November 2004. Available online 16 February 2005.
Abstract
Minocycline is neuroprotective in many experimental models of neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of viral encephalitis. Experimental infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal encephalitis caused by neuronal apoptosis throughout the CNS. Minocycline significantly delayed death in mice to 11.6 ± 0.9 days post-infection vs. 8.6 ± 0.7 days post-infection in controls (P < 0.01). Virus-induced CNS injury, apoptosis, viral titer and antigen expression were significantly decreased in the brains of minocycline-treated mice on 6 and 8 days post-infection compared to controls. Virus-induced injury and viral titer in minocycline-treated infected mice at 11 days post-infection were similar to those seen in untreated T3D-infected mice at 8 days post-infection. Little microglial or astrocytic invasion of brain regions with viral injury was found at any time-point in untreated or minocycline-treated mice, suggesting that in this model system the neuroprotective effect exerted by minocycline is more likely due to its anti-apoptotic properties rather than its capacity to inhibit microglial activation and limit gliosis. These findings, similar to those reported for neurodegenerative diseases, indicate that minocycline does not prevent development of fatal reovirus encephalitis but delays disease onset and progression, suggesting that minocycline treatment may provide a useful adjunctive therapy in viral CNS infections.
Keywords: Apoptosis; Central nervous system; Microglia; Neurons; Mouse
Lisää minosykliinin käytöstä keskushermostoperäisissä virustaudeissa:
http://www.sciencedirect.com/science?_o ... 7%23579292!
Minocycline delays disease onset and mortality in reovirus encephalitis
Sarah M. Richardson-Burns and Kenneth L. Tyler
aNeuroscience Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA
bDepartments of Neurology, Medicine, Immunology, and Microbiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA
cDenver Veteran's Affairs Medical Center, Denver, CO 80220, USA
Received 7 September 2004; revised 2 November 2004; accepted 9 November 2004. Available online 16 February 2005.
Abstract
Minocycline is neuroprotective in many experimental models of neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of viral encephalitis. Experimental infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal encephalitis caused by neuronal apoptosis throughout the CNS. Minocycline significantly delayed death in mice to 11.6 ± 0.9 days post-infection vs. 8.6 ± 0.7 days post-infection in controls (P < 0.01). Virus-induced CNS injury, apoptosis, viral titer and antigen expression were significantly decreased in the brains of minocycline-treated mice on 6 and 8 days post-infection compared to controls. Virus-induced injury and viral titer in minocycline-treated infected mice at 11 days post-infection were similar to those seen in untreated T3D-infected mice at 8 days post-infection. Little microglial or astrocytic invasion of brain regions with viral injury was found at any time-point in untreated or minocycline-treated mice, suggesting that in this model system the neuroprotective effect exerted by minocycline is more likely due to its anti-apoptotic properties rather than its capacity to inhibit microglial activation and limit gliosis. These findings, similar to those reported for neurodegenerative diseases, indicate that minocycline does not prevent development of fatal reovirus encephalitis but delays disease onset and progression, suggesting that minocycline treatment may provide a useful adjunctive therapy in viral CNS infections.
Keywords: Apoptosis; Central nervous system; Microglia; Neurons; Mouse