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1. 女性における慢性骨盤痛の治療 treatment of chronic pelvic pain in women
2. 癌疼痛のマネージメント：介入的治療 cancer pain management interventional therapies

English Journal

Sera from patients with seropositive neuromyelitis optica spectral disorders caused the degeneration of rodent optic nerve.

Matsumoto Y1, Kanamori A2, Nakamura M1, Takahashi T3, Nakashima I3, Negi A1.Author information 1Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.2Division of Ophthalmology, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Electronic address: kanaaki@med.kobe-u.ac.jp.3Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.AbstractNeuromyelitis optica (NMO) is an autoimmune inflammatory, neurodestructive disease primarily targeting the optic nerve and spinal cord. An autoantibody against water channel protein aquaporin-4 (AQP4), which is expressed at endofeet of astrocytes has been implicated in the pathogenesis of NMO. We evaluated the impact of sera of seropositive patients with NMO spectrum disorders (NMOSDs) on the rodent optic nerve and retina. Serum was obtained either from patients with seropositive NMOSD (AQP4+), seronegative patient with idiopathic optic neuritis (AQP4-), and healthy volunteers (control). Anti-AQP4 antibody in a serum was measured by a previously established cell-based assay. The patients' sera were applied on the optic nerve after de-sheathed. Immunohistochemistry showed that at 7 days after the treatment, the area of the optic nerve exposed to the AQP4+ sera lost expression of both AQP4 and glial fibrillary acidic protein. Also, Human-IgG immunoreactivity and marked invasion of inflammation cells were observed in the optic nerve treated with AQP4+ serum. Immnoreactivity of neurofilament was reduced at 14 days after the treatment, not 7 days. Real-time polymerase chain reaction revealed the reduced gene expression of neurofilament in retina from the eye that was exposed to the AQP4+ sera at 14 days. Retrograde fluorogold-labeling on the retinal flatmount disclosed the significantly reduced number of retinal ganglion cells when the AQP4+ sera were applied. The present model has demonstrated that the sera from patients with seropositive NMOSDs led to the regional astrocytic degeneration and inflammatory cell invasion in the optic nerve, resulting in the ultimate loss of RGCs and their axons at areas beyond the injury site.
Experimental eye research.Exp Eye Res.2013 Dec 24;119C:61-69. doi: 10.1016/j.exer.2013.12.010. [Epub ahead of print]
Neuromyelitis optica (NMO) is an autoimmune inflammatory, neurodestructive disease primarily targeting the optic nerve and spinal cord. An autoantibody against water channel protein aquaporin-4 (AQP4), which is expressed at endofeet of astrocytes has been implicated in the pathogenesis of NMO. We ev
PMID 24374258

The crystal structure of human quinolinic acid phosphoribosyltransferase in complex with its inhibitor phthalic acid.

Malik SS, Patterson DN, Ncube Z, Toth EA.Author information Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201.AbstractQuinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step of the de novo NAD+ biosynthesis pathway. This puts QPRT at the junction of two different pathways, that is, de novo NAD+ biosynthesis and the kynurenine pathway of tryptophan degradation. Thus, QPRT is an important enzyme in terms of its biological impact and its potential as a therapeutic target. Here, we report the crystal structure of human QPRT bound to its inhibitor phthalic acid (PHT) and kinetic analysis of PHT inhibition of human QPRT. This structure, determined at 2.55 Å resolution, shows an elaborate hydrogen bonding network that helps in recognition of PHT and consequently its substrate QA. In addition to this hydrogen bonding network, we observe extensive van der Waals contacts with the PHT ring that might be important for correctly orientating the substrate QA during catalysis. Moreover, our crystal form allows us to observe an intact hexamer in both the apo- and PHT-bound forms in the same crystal system, which provides a direct comparison of unique subunit interfaces formed in hexameric human QPRT. We call these interfaces "nondimeric interfaces" to distinguish them from the typical dimeric interfaces observed in all QPRTs. We observe significant changes in the nondimeric interfaces in the QPRT hexamer upon binding PHT. Thus, the new structural and functional features of this enzyme we describe here will aid in understanding the function of hexameric QPRTs, which includes all eukaryotic and select prokaryotic QPRTs. Proteins 2013; © 2013 Wiley Periodicals, Inc.
Proteins.Proteins.2013 Aug 28. doi: 10.1002/prot.24406. [Epub ahead of print]
Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step of the de novo NAD+ biosynthesis pathway. This puts QPRT at the junction of two different pathways, that is, de novo NAD+ biosynthesis and
PMID 24038671

The impact of neuroimmune changes on development of amyloid pathology; relevance to Alzheimer's disease.

Lynch MA.Author information Trinity College Institute for Neuroscience, Trinity College, Dublin 2, Ireland.AbstractNeuroinflammatory changes are a characteristic of several, if not all, neurodegenerative diseases including Alzheimer's disease (AD) and are typified by increased microglial activation. Microglia express several receptors making them highly reactive and plastic cells, and, at least in vitro, they adopt different phenotypes in a manner analogous to their peripheral counterparts, macrophages. Microglia also express numerous cell surface proteins enabling them to interact with cells and the evidence indicates that maintenance of microglia in a quiescent state relies, at least to some extent, on an interaction with neurons by means of specific ligand-receptor pairs for example CD200-CD200R. It is clear that microglia also interact with T cells and recent evidence indicates that co-incubation of microglia with Th1 cells markedly increase their activatioñ Under normal conditions, small numbers of activated T cells gain entry to the brain and are involved in immune surveillance but infiltration of significant numbers of T cells occurs in disease and following injury. The consequences of T cell infiltration appear to depend on the conditions, with descriptions of both neurodestructive and neuroprotective effects in animal models of different diseases. This review will discuss the modulatory effect of T cells on microglia and impact of infiltration of T cells into the brain with a focus on AD and will propose that infiltration of interferon (IFN)-γ-producing cells may be an important factor in triggering inflammation that is pathogenic and destructive. This article is protected by copyright. All rights reserved.
Immunology.Immunology.2013 Jul 23. doi: 10.1111/imm.12156. [Epub ahead of print]
Neuroinflammatory changes are a characteristic of several, if not all, neurodegenerative diseases including Alzheimer's disease (AD) and are typified by increased microglial activation. Microglia express several receptors making them highly reactive and plastic cells, and, at least in vitro, they ad
PMID 23876085