These findings suggest that a chloride channel inhibitor can control IL-13-mediated airway features at least by suppressing JAK/STAT6 activation.

Neuromedin U (NMU) is a neuropeptide expressed not only in the central nervous system but also in various organs, including the gastrointestinal tract and lungs. NMU interacts with two G protein-coupled receptors, NMU-R1 and NMU-R2. Although NMU-R2 is expressed in a specific region of the brain, NMU-R1 is expressed in various peripheral tissues, including immune and hematopoietic cells. Our recent study demonstrated an important role of NMU in mast cell-mediated inflammation. In this study, we showed that airway eosinophilia was reduced in NMU-deficient mice in an allergen-induced asthma model. There were no differences in the antigen-induced Th2 responses between wild-type and NMU knockout mice. NMU-R1 was highly expressed in the eosinophil cell line, and NMU directly induced Ca(2+) mobilization and extracellular/signal-regulated kinase phosphorylation. NMU also induced cell adhesion to components of the extracellular matrix (fibronectin and collagen type I), and chemotaxis in vitro. Furthermore, NMU-R1 was also expressed in human peripheral blood eosinophils, and NMU induced cell adhesion in a dose-dependent manner. These data indicate that NMU promotes eosinophil infiltration into inflammatory sites by directly activating eosinophils. Our study suggests that NMU receptor antagonists could be novel targets for pharmacological inhibition of allergic inflammatory diseases, including asthma.

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Abstract. We investigated the chronic functional and histopathological changes in the sciatic nerve and lens of streptozotocin (STZ)-diabetic rats and evaluated the preventive effects of ranirestat (AS-3201), a potent aldose reductase inhibitor, on these changes. Sorbitol levels in the sciatic nerve and lens, motor nerve conduction velocity (MNCV), and development of cataracts were measured in STZ-diabetic rats given a ranirestat-admixed diet (0.0005%) for 35 weeks. Ranirestat reduced sorbitol accumulation in the sciatic nerve and improved the decrease in MNCV of STZ-diabetic rats. Morphological and morphometric examination of changes in sural nerve revealed that treatment with ranirestat prevented both the deformity of myelinated fibers and the decrease in their axonal and myelin areas (atrophy). Ranirestat also averted the changes in the size frequency histogram of myelinated fibers. Finally, STZ-diabetic rats developed early lens opacities 8 weeks after STZ injection and had cataract by the end of the experimental period. However, in the ranirestat-treated diabetic rats, no lens opacity was observed in any rat throughout the entire experimental period. This study suggests that the polyol pathway plays an important role in the progress of diabetic neuropathy and cataract formation in STZ-diabetic rats. Ranirestat should be a promising agent for the treatment of complications associated with diabetes, especially neuropathy.

The authors recently succeeded in growing two-dimensional ZnO nanowalls on sapphire substrates using high-pressure pulsed laser deposition (PLD) without any catalysts. Depending on the PLD growth conditions and the composition of the target, ZnO nanowalls with thickness of tens of nanometers and dimension of several micrometers were synthesized reproducibly. Most of the nanowalls were vertically epitaxial on the c-cut sapphire substrates with a preferred c-axis orientation as confirmed with X-ray diffraction and transmission electron microscopy. The room temperature photoluminescence spectrum of such a ZnO nanowall exhibited a strong intrinsic UV emission and a week defect-related visible emission. It was found that the ZnO nanowalls showed stable field emission properties with low threshold field and a big field enhancement factor. Photocurrent measurements also indicated that these ZnO nanowall films showed a high sensitivity to UV light, which can be used as a UV photodetector.

Dengue virus (DV) belongs to the family Flaviviridae, and its infection is characterized by dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. Some flaviviruses, such as Japanese encephalitis, St. Louis encephalitis, Murray Valley encephalitis, and West Nile viruses, have the common feature of neurovirulence in the human CNS, including poliomyelitis-like syndrome. 1 We report a patient with dengue fever who developed gray matter myelitis.Case report. A 42-year-old Japanese man working in Indonesia was admitted to a local hospital because of fever (38°C). Three days after admission, he had weakness in both legs and retained urine, and he was transferred to Singapore General Hospital. On admission, he was febrile and had a generalized macular rash. There was flaccid paralysis of the lower limbs with absent knee and ankle jerks. Sensation to pinprick was decreased below T6 segment. Laboratory examination revealed thrombocytopenia. Results of CSF examination were as follows: cells, 201/mm 3 (mononuclear cell dominant); glucose, 1.6 mmol/L; and protein, 100 mg/dL (normal, Ͻ45). The antibody index (normal, Ͻ1.00) ratio of anti-DV immunoglobulin (Ig) M to IgG was 3.32/1.64 in serum and was 6.02/1.37 in CSF. Results of plague neutralization assays indicated the presence of antibodies to DV type 1. The following serologies were all negative: antinuclear antibody, anti-doublestranded DNA, antiganglioside antibody, Venereal Disease Research Laboratory tests, poliovirus, HIV, human T-cell leukemia virus I, measles, mumps, rubella, yellow fever, enterovirus, herpes simplex virus, cytomegalovirus, and Epstein-Barr virus. CSF was negative for herpes simplex virus and enterovirus by PCR and culture and negative for a panel of neurotropic viruses (e.g., yellow fever, measles, mumps, and Japanese encephalitis virus) by complement fixation. CSF was also negative for oligoclonal bands, myelin basic protein, and fungi, mycobacteria, and bacteria by culture. MRI of the spine revealed swelling and an extensive high T2-weighted signal from the cervical spine to the conus medullaris. The patient was started on IV methylprednisolone and antibiotics. Two days after transfer, he developed respiratory distress and was intubated. He was normally alert but had complete tetraplegia and bilateral facial weakness. Further deterioration was evidenced by loss of upper limb reflexes and the ability only to grimace. He was started on IVIg, followed by plasmapheresis. Muscle weakness in face and neck gradually improved. He was transferred to Tokushima University Hospital during the third week of his illness. There was complete tetraplegia and mild sensory disturbance below the C7 segment. Routine blood examination was normal. CSF examination was as follows: 5 cells/mm 3 ; protein, 530 mg/dL; and IgG-albumin index, 0.958 (normal, Ͻ0.7). EMG showed moderate numbers of fibrillations in four extremities, indicating active denervation. Results of motor nerve conduction velocities were normal, but compound muscle action potential (CMAP) ampl...

The mechanism of the unique dynamic electron polarization of the quartet (S = 3/2) high-spin state via a doublet-quartet quantum-mixed state and detail theoretical calculations of the population transfer are reported. By the photo-induced electron transfer, the quantum-mixed charge-separate state is generated in acceptor-donor-radical triad (A-D-R). This mechanism explains well the unique dynamic electron polarization of the quartet state of A-D-R. The generation of the selectively populated quantum-mixed state and its transfer to the strongly coupled pure quartet and doublet states have been treated both by a perturbation approach and by exact numerical calculations. The analytical solutions show that generation of the quantum-mixed states with the selective populations after de-coherence and/or accompanying the (complete) dephasing during the charge-recombination are essential for the unique dynamic electron polarization. Thus, the elimination of the quantum coherence (loss of the quantum information) is the key process for the population transfer from the quantum-mixed state to the quartet state. The generation of high-field polarization on the strongly coupled quartet state by the charge-recombination process can be explained by a polarization transfer from the quantum-mixed charge-separate state. Typical time-resolved ESR patterns of the quantum-mixed state and of the strongly coupled quartet state are simulated based on the generation mechanism of the dynamic electron polarization. The dependence of the spectral pattern of the quartet high-spin state has been clarified for the fine-structure tensor and the exchange interaction of the quantum-mixed state. The spectral pattern of the quartet state is not sensitive towards the fine-structure tensor of the quantum-mixed state, because this tensor contributes only as a perturbation in the population transfer to the spin-sublevels of the quartet state. Based on the stochastic Liouville equation, it is also discussed why the selective population in the quantum-mixed state is generated for the "finite field" spin-sublevels. The numerical calculations of the elimination of the quantum coherence (de-coherence and/or dephasing) are demonstrated. A new possibility of the enhanced intersystem crossing pathway in solution is also proposed.

Objectives Cancer Risk and SurveillancePatients with longstanding extensive ulcerative colitis are at increased risk of developing colorectal cancer. Colonoscopic surveillance is recommended by most authorities in an attempt to reduce the associated mortality. Surveillance relies on the detection of premalignant dysplastic tissue, and where dysplasia is detected, proctocolectomy has historically been and currently remains the management of choice, although there is increasing evidence that adenoma-like dysplastic lesions may safely be resected endoscopically. Detection of Dysplasia in Ulcerative ColitisIn patients without ulcerative colitis, the premalignant dysplastic lesion, the adenoma, usually occurs as a clearly delineated macroscopically visible abnormality. However, in ulcerative colitis there is no clear-cut adenoma±carcinoma sequence. Dysplasia can occur in polypoid lesions, but often appears as a more subtle mucosal irregularity, or may be macroscopically invisible. Because of this, most endoscopists worldwide take multiple random biopsies of flat mucosa. It has been estimated that 33 biopsies are required to provide a 90 % chance of finding the highest degree of dysplasia present [1]. It has been recommended that four random biopsies per site over nine sites throughout the colon be undertaken, with increased sampling from the rectosigmoid and with additional biopsies from raised or suspicious lesions [2]. However, it is time-consuming to take 30 ± 50 nontargeted random biopsies throughout the colon, and dysplastic lesions might still be overlooked.Recent improvements in endoscopic equipment and technique, particularly the use of dyesprays (chromoendoscopy), have improved dysplasia detection in ulcerative colitis [3 ± 5],