Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury.

We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not met-hemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.

Performance of a helical undulator of the UVSOR.

A helical undulator was installed in the 0.75 GeV storage ring of the UVSOR facility of the Institute for Molecular Science. The undulator was designed to produce the fundamental of the circularly polarized undulator radiation in the energy range 2-43 eV, and the higher harmonics with elliptical polarization in the energy range up to 300 eV. Recently, the first spectrum from the undulator was observed. The performance of the undulator and the obtained spectrum are reported.

Cardiotoxicity of combined administration of adriamycin and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rats-with special reference to 125I-MIBG cardioautoradiography and histopathological findings.

We studied whether adriamycin(ADM)-induced myocardial disorder in rats is advanced when recombinant human granulocyte colony-stimulating factor (rhG-CSF) is administered. Rats were divided into three groups (15 rats/group), i.e. the ADM group, the ADM+rhG-CSF group, and the vehicle-treated control group. ADM (2 mg/kg, i.p.) was administered for the first 2 days in each cycle and 10 days of administration of rhG-CSF (50 micrograms/kg, s.c.) was started two days after the second dose of ADM was given in each cycle. The dosing cycle was repeated 3 times. One day after the last dose, the following parameters were analyzed: peripheral blood and bone marrow cells, electrocardiogram (ECG) and histopathological findings. Four hours after intravenous administration of 125I-metaiodobenzylguanidine (125I-MIBG), accumulation of 125I-MIBG in some organs and findings from autoradiography (ARG) of the heart were examined. ECG revealed an extended ventricular activation (VAT) time in the ADM and ADM+rhG-CSF groups. In histopathological analysis, vacuolar degeneration of the myocardium was observed in both the ADM and ADM+rhG-CSF groups. The degree of change was the same for both groups. The accumulation of 125I-MIBG in the heart was lower in both the ADM and ADM+rhG-CSF groups than in the control group. The same tendency was observed in ARG, but the difference between the ADM group and the ADM+rhG-CSF group was not significant. These results suggest that administration of rhG-CSF at the standard clinical dose does not aggravate ADM-induced myocardial disorder. However, because this disorder may be more clearly manifested by treatment with higher doses of ADM, it is necessary to conduct further studies on the methods of dosing and administration.