Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme

NADPH oxidase is a superoxide (O₂^•−)-generating enzyme first identified in phagocytes, essential for their bactericidal activities. Later, in non-phagocytes, production of O₂^•− was also demonstrated in an NADPH-dependent manner. In the last decade, several non-phagocyte-type NADPH oxidases have been identified. The catalytic subunit of these oxidases, NOX, constitutes the NOX family. There are five homologs in the family, NOX1 to NOX5, and two related enzymes, DUOX1 and DUOX2. Transgenic or gene-disrupted mice of the NOX family have also been established. NOX/DUOX proteins possess distinct features in the dependency on other components for their enzymatic activities, tissue distributions, and physiological functions. This review summarized the characteristics of the NOX family proteins, especially focused on their functions clarified through studies using gene-modified mice.     

Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia

We investigated whether the mobilization of endothelial progenitor cells (EPCs) by exogenous erythropoietin (Epo) promotes the repair of injured endothelium. Recombinant human Epo was injected (1000 IU/kg for the initial 3 days) after wire injury of the femoral artery of mice. Neointimal formation was inhibited by Epo to 48% of the control (P<0.05) in an NO-dependent manner. Epo induced a 1.4-fold increase in reendothelialized area of day 14 denuded vessels, 55% of which was derived from bone marrow (BM) cells. Epo increased the circulating Sca-1(+)/Flk-1(+) EPCs (2.0-fold, P<0.05) with endothelial properties NO dependently. BM replacement by GFP- or beta-galactosidase-overexpressing cells showed that Epo stimulated both differentiation of BM-derived EPCs and proliferation of resident ECs. BM-derived ECs increased 2.2- to 2.7-fold (P<0.05) in the Epo-induced neoendothelium, where the expression of Epo receptor was upregulated. Epo induced Akt/eNOS phosphorylation and NO synthesis on EPCs and exerted an antiapoptotic action on wire-injured arteries. In conclusion, Epo treatment inhibits the neointimal hyperplasia after arterial injury in an NO-dependent manner by acting on the injured vessels and mobilizing EPCs to the neo-endothelium.     

Quantitative assessment of image noise and streak artifact on CT image: Comparison of z-axis automatic tube current modulation technique with fixed tube current technique

The purpose of our study is to quantitatively assess the effects of z-axis automatic tube current modulation technique on image noise and streak artifact, by comparing with fixed tube current technique. Standard deviation of CT-values was employed as a physical index for evaluating image noise, and streak artifact was quantitatively evaluated using our devised Gumbel evaluation method. z-Axis automatic tube current modulation technique will improve image noise and streak artifact, compared with fixed tube current technique, and will make it possible to significantly reduce radiation doses at lung levels while maintaining the same image quality as fixed tube current technique.     

Endoscopic tumor ablation for laryngotracheal intraluminal invasion secondary to advanced thyroid cancer

CONCLUSIONS: Endoscopic tumor ablation is a valuable option for inoperable postoperative laryngotracheal intraluminal invasion of well-differentiated thyroid carcinoma (DTC). OBJECTIVES: To investigate whether DTC invasion to the laryngotracheal mucosa can be controlled by 'simple' tumor ablation considering its relatively slow-growing nature. PATIENTS AND METHODS: Twenty-two consecutive patients underwent endoscopic tumor ablation caused by DTC for local control of intraluminal lesions with no significant extrinsic laryngotracheal compression in symptomatic or asymptomatic patients in whom radical operations were contraindicated. Debulking by Nd:YAG laser was followed by electrocoagulation and microwave coagulation for the residual tumor base. RESULTS: The critical complication, post-treatment supraglottic stenosis, was managed by prophylactic minitracheotomy. During the follow-up period of up to 125 months, 6 of 22 patients died (median survival 50 months), mainly of lung metastases, but all had a patent airway at death. Post-surgical extraluminal lesion growth is indolent and since relapse of the intraluminal lesion is the main cause of symptoms, satisfactory local control could be obtained by re-ablation of the mucosal lesion every few years. Lesions requiring retreatment within 1 year after initial treatment usually have high-grade malignancy, causing extrinsic compression, and prognosis is unfavorable.     

Determination of reference intervals for vibratory perception thresholds of the lower extremities in normal subjects

The assessment of vibratory perception thresholds (VPTs) is important for evaluating human somatosensory functions and provides new aspects in clinical practice and research. However, there has been little information concerning determinants of the VPT in normal individuals, and there has been no investigation to determine the reference intervals for the lower extremities by vibrometers using appropriate statistical analysis. We determined reference intervals for the VPT in lower extremities of 377 healthy subjects (241 males, 136 females; ages 11–74 years) using Suzuki-Matsuoka vibrometer-5 according to the National Committee for Clinical Laboratory Standards guidelines. The VPT was measured at 12 points: ulnar styloids, patellae, medial and lateral malleoli and the tip of the great toes, dorsal aspect of the distal phalanx of the fifth toes. The effects of age, sex, height, weight, alcohol consumption, and smoking on the VPTs were also investigated. The VPTs of normal subjects increased significantly with age. The difference between the two sides was negligible for determining reference intervals of the VPT. The average VPT was higher in men than in women at the lateral malleolus, the great toe, the patella, and the ulnar styloid but not significantly different at the fifth toe or the medial malleolus. There were no significant differences in the VPTs among the four sites of the foot. The reference interval for the VPT of the lower extremity is less than 13 × 10⁻² G. The influence of body mass index, smoking, and alcohol consumption on the VPT was not significant. We provide the reference interval for the VPT of lower extremities in normal subjects. This information can serve as a basis for future clinical applications of VPT measurements.An erratum to this article can be found at     

Antioxidants suppress plasma levels of lectinlike oxidized low-density lipoprotein receptor-ligands and reduce atherosclerosis in watanabe heritable hyperlipidemic rabbits

Oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. In this study, we investigated the effects of antioxidants including probucol, vitamin E, and fluvastatin, an HMG-CoA (hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor with antioxidative property, on plasma levels of oxidized LDL (OxLDL) during the progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. OxLDL were measured as ligand for lectin-like OxLDL receptor-1 (LOX-1). LOX-1-ligand was higher in WHHL rabbits than in control rabbits as early as 2 months of age and was sustained throughout the experimental period. Supplementation of probucol (1%) and vitamin E (0.5%) to the diet reduced LOX-1-ligand but had little effect on total cholesterol (T-CHO). Fluvastatin (0.03%) significantly reduced both LOX-1-ligand and T-CHO. The extent of reduction in T-CHO was less prominent than in the case of LOX-1-ligand. All of the agents reduced the atherosclerotic lesion area and lipid contents of aortic arches. These parallel results indicate that oxidatively modified LDL elevated in the early stages of atherogenesis is of functional importance in the progression of the disease and can be suppressed by antioxidant treatment. Furthermore, fluvastatin may reduce the evolution of atherosclerosis, not only by lowering plasma cholesterol but also by reducing oxidative modification of LDL.     

Inhibitory effect of orally administered aldose reductase inhibitor SNK-860 on corneal polyol accumulation in galactose-fed rats

· Background: Diabetic keratopathy, frequently observed after vitreous surgery, has been thought to be related to the aldose reductase-catalyzed reaction. However, few reports have been published on the chronological changes in polyol accumulation and the effect of the aldose reductase inhibitor in the corneal epithelium or endothelium of galactosemic rats. Consequently, the polyol accumulation in corneal epithelium and endothelium with stroma of 50% galactose-fed rats and the preventive effect of an aldose reductase inhibitor, SNK-860, were biochemically analyzed. · Methods: Four-week-old male Sprague-Dawley rats were fed a 50% galactose diet without supplement or supplemented with a low (3 mg/kg b.w.) or high (30 mg/kg b.w.) dose of SNK-860 (Sanwa Kagaku Kenkyusho, Japan), or a normal diet. Polyol contents in the corneal epithelium or endothelium with stroma were individually measured using gas-liquid chromatography. · Results: Polyol in corneal epithelia accumulated quickly in the 1st week, reached a maximum at the 3rd week of feeding and then gradually decreased. Low- and high-dose SNK-860 treatment significantly inhibited polyol accumulation in the epithelium and endothelium with stroma, respectively. Changing to the normal or SNK-860 supplemented diets significantly inhibited polyol accumulation. · Conclusion: This finding indicates that oral administration of a new aldose reductase inhibitor, SNK-860, or systematic treatment of diabetes may be effective in preventing polyol pathway-induced corneal damage by quickly reducing the polyol level. Received: 17 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998