Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.

The decomposition of hypochlorous acid in the neutral pH region was studied in 1.0 M NaC104 from 15 to 50 °C. The pAa of HOC1 was also determined under these conditions. Hypochlorous acid has a maximum decomposition rate at pH 6.89. The decomposition is a third-order process. The values of AH* and AS* are 64.0 ± 0.6 kJ/mol and -67 ± 2 J/mol K, respectively. A mechanism for the decomposition of HOC1 is proposed involving C120-H20 and C102~a s intermediates. Rate constants for the rate-determining steps of the mechanism are presented. Above pH 6, the rate-determining step is proposed to be as follows: OCh + C120-H20 -HC1202~+ HOC1. Below pH 6, this process is proposed to be in competition with a parallel pathway: HOC1 + 020• 20 -» H2C1202 + HOC1.The proposed mechanism was tested by mathematical simulation of the experimental data using the GEAR algorithm. The simulation gives additional support for the proposed mechanism.

A low-loss and highly birefringent polarization maintaining photonic crystal fiber has been fabricated. The fiber loss and modal birefringence at 1550 nm were 1.3 dB/km and 1.4x10 -3 , respectively.

Urinary retention is a common complication after anorectal surgery. It is linked to several risk factors, including increased intravenous fluids and postoperative pain. Perioperative fluid restriction and adequate pain relief appear to be effective in preventing urinary retention in a significant number of patients after anorectal surgery.

In three alternative splice variants of Homer 1 transcripts, Homer 1a mRNA has been shown to be upregulated selectively and rapidly by neural stimulation and represents a member of the immediate early gene (IEG) family. We investigated the mechanism underlying Homer 1a mRNA induction in cerebellar granule cell culture. All Homer 1 variants were expressed in cultured granule cells as analyzed by RNA blotting and immunochemical characterization. Glutamate stimulation of granule cells selectively upregulated Homer 1a mRNA via NMDA receptor-mediated influx of extracellular calcium. The induction of Homer 1a mRNA was much slower (peaked at 4 hr) and sustained longer than that of the typical IEG c-fos mRNA. Actinomycin D and cycloheximide experiments have revealed that, despite the presence of the mRNA-destabilizing AU-rich motif, transcriptional activation is a main determinant for selective Homer 1a mRNA induction. Inhibitor analysis as well as immunochemical characterization has indicated that the MEK (MAPK/ERK kinase)-ERK (extracellular signal-regulated kinase) cascade plays an indispensable role in glutamate-stimulated induction of Homer 1a mRNA. Consistent with this observation, brain-derived neurotrophic factor, which is known to activate the ERK cascade, similarly upregulated Homer 1a mRNA. These results demonstrate that MAPK (mitogen-activated protein kinase) is a key mediator that links distinct extracellular stimuli to the transcriptional activation of Homer 1a mRNA.