Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia.

In the present study, experiments were performed to explore the action of quercetin, the most widely distributed flavonoids, and its major metabolite, quercetin-3'-sulfate, on lipopolysaccharide (LPS)- and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) production in BV-2 microglia. Quercetin could suppress LPS- and IFN-gamma-induced NO production and inducible nitric oxide synthase (iNOS) gene transcription, while quercetin-3'-sulfate had no effect. LPS-induced IkappaB kinase (IKK), nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation, and IFN-gamma-induced NF-kappaB, signal transducer and activator of transcription-1 (STAT1) and interferon regulatory factor-1 (IRF-1) activation were reduced by quercetin. Moreover quercetin was able to induce heme oxygenase-1 expression. To address the involvement of heme oxygenase-1 induction in iNOS inhibition, heme oxygenase-1 antisense oligodeoxynucleotide was used. Quercetin-mediated inhibition of NO production and iNOS protein expression were partially reversed by heme oxygenase-1 antisense oligodeoxynucleotide, but was mimicked by hemin, a heme oxygenase-1 inducer. The involvement of signal pathways in quercetin-induced heme oxygenase-1 gene expression was associated with tyrosine kinase and mitogen-activated protein kinases activation. All these results suggest quercetin should provide therapeutic benefits for suppression of inflammatory-related neuronal injury in neurodegenerative diseases.

Usefulness of Tc-99m HMPAO-labeled WBC heart scan to predict impaired ventricular function and coronary artery dilation in children with Kawasaki disease.

Forty-nine children with Kawasaki disease were included in this study. Based on the severity of carditis as determined by Tc-99m HMPAO-labeled WBC heart scan, the children were separated into two groups. Group A (n=24) had significant carditis and group B (n=25) did not have significant carditis. The left and right ventricular ejection fractions (LVEF and RVEF) were evaluated by equilibrium multigated blood pooling ventriculography. Diameters of the left and right coronary arteries (LCA and RCA) were measured by two-dimensional echocardiography. The results showed that group A had lower LVEF and RVEF, but larger diameters of the LCA and RCA than those of group B patients. The sensitivity of significant carditis to predict left ventricular dysfunction, right ventricular dysfunction, LCA dilation and RCA dilation was 88.9, 70.6, 75, and 71.4%, respectively; the specificities were 100, 100, 100, and 67.9%, respectively. Our findings suggest that significant carditis determined by Tc-99m HMPAO-labeled WBC heart scan can accurately predict impaired ventricular function and coronary artery dilation.

Technetium-99m tetrofosmin myocardial perfusion single photon emission computed tomography in syndrome X: a preliminary report.

Syndrome X is used to describe patients with chest pain and a normal coronary angiogram. We reviewed technetium-99m tetrofosmin (Tc-99m TF) myocardial perfusion single photon emission computed tomography (SPECT) results and clinical data of 43 syndrome X patients and 30 healthy controls with normal left ventricular ejection fraction and no cardiac abnormalities. The Tc-99m TF myocardial perfusion SPECT results showed 12 (27.9%) syndrome X patients had normal myocardial perfusion and 31 (72.1%) had abnormal myocardial perfusion, including 6 (14.0%) patients with fixed defects. 20 (46.5%) patients with transient defects, and 5 (11.6%) patients with reverse defects. The results of exercise ECG were not related to perfusion defects in Tc-99m TF myocardial perfusion SPECT. In contrast, all of the 30 (100.0%) healthy controls had normal myocardial perfusion SPECT results. We conclude that abnormal Tc-99m TF myocardial perfusion SPECT is common in syndrome X and does not correlate well with the exercise ECG. However, further studies with larger case numbers and long term follow up in patients with myocardial events are necessary to support our findings.

Single photon emission computed tomography of technetium-99m tetrofosmin myocardial perfusion imaging in patients with systemic lupus erythematosus--a preliminary report.

The purpose of this study was to evaluate the utility of single-photon emission computed tomography (SPECT) of technetium-99m tetrofosmin (Tc-99m TF) myocardial perfusion imaging to detect myocardial involvement in patients with systemic lupus erythematosus (SLE). Three groups of subjects-group 1: 25 SLE female patients with non-specific cardiac symptoms and signs, group 2: 25 female SLE patients without any cardiac symptoms and signs, and group 3: 25 female healthy controls-were evaluated by comparing rest and dipyridamole-stress Tc-99m TF myocardial perfusion SPECT. Tc-99m TF myocardial perfusion SPECT revealed perfusion defects in 88% and 40% of the cases in groups 1 and 2. respectively. However, no cases in group 3 demonstrated myocardial perfusion defects. Tc-99m TF myocardial perfusion SPECT is a useful noninvasive imaging modality to detect cardiac involvement in SLE patients with or without cardiac symptoms and signs.