Arteriomenterial compression.

High density lipoprotein (HDL) is the major carrier of lipid hydroperoxides in plasma, but it is not yet established whether HDL proteins are damaged by reactive nitrogen species in the circulation or artery wall. One pathway that generates such species involves myeloperoxidase (MPO), a major constituent of artery wall macrophages. Another pathway involves peroxynitrite, a potent oxidant generated in the reaction of nitric oxide with superoxide. Both MPO and peroxynitrite produce 3-nitrotyrosine in vitro. To investigate the involvement of reactive nitrogen species in atherogenesis, we quantified 3-nitrotyrosine levels in HDL in vivo. The mean level of 3-nitrotyrosine in HDL isolated from human aortic atherosclerotic intima was 6-fold higher (619 +/- 178 micromol/mol Tyr) than that in circulating HDL (104 +/- 11 micromol/mol Tyr; p < 0.01). Immunohistochemical studies demonstrated striking colocalization of MPO with epitopes reactive with an antibody to 3-nitrotyrosine. However, there was no significant correlation between the levels of 3-chlorotyrosine, a specific product of MPO, and those of 3-nitrotyrosine in lesion HDL. We also detected 3-nitrotyrosine in circulating HDL, and linear regression analysis demonstrated a strong correlation between the levels of 3-chlorotyrosine and levels of 3-nitrotyrosine. These observations suggest that MPO promotes the formation of 3-chlorotyrosine and 3-nitrotyrosine in circulating HDL but that other pathways also produce 3-nitrotyrosine in atherosclerotic tissue. Levels of HDL isolated from plasma of patients with established coronary artery disease contained twice as much 3-nitrotyrosine as HDL from plasma of healthy subjects, suggesting that nitrated HDL might be a marker for clinically significant vascular disease. The detection of 3-nitrotyrosine in HDL raises the possibility that reactive nitrogen species derived from nitric oxide might promote atherogenesis. Thus, nitrated HDL might represent a previously unsuspected link between nitrosative stress, atherosclerosis, and inflammation.

Arteries↗

PubMed2004

Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma.

AIM: To evaluate the therapeutic efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chemoembolization (TACE) on the patients with hepatocellular carcinoma (HCC). METHODS: Between 1998 and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63 patients had a Okuda stage I lesion and 31 patients had stage II. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver cirrhosis was present in all the patients. There were 43 cases of class A and 51 class B. TACE was performed using lipiodol, 5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d). RESULTS: The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overall survival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 mo. On univariate analysis, age (P=0.026), Child-Pugh classification for cirrhosis of liver (P=0.010), Okuda stage (P=0.026), tumor size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose (P=0.000) proved to be significant factors for survival. On multivariate analysis, age (P=0.024), radiation dose (P=0.001), and tumor size (P=0.000) were the significant factors. CONCLUSION: 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy.

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