Conclusion:Antioxidant consumption can acutely restore endothelial dysfunction in elderly patients.Summary: Endothelial dysfunction likely contributes to atherosclerosis through a reduction in bioavailability of nitrite oxide (NO). There is also an age-related increase in plasma free radical concentration that contributes to a decrease in the bioavailability of NO. The authors investigated whether acute antioxidant treatment would result in a reversal of the decrease in endothelial function in elderly patients. As markers of endothelial function, the authors used flow-mediated vasodilatation and reactive hyperemia, which were evaluated after the individual consumed placebo or an oral antioxidant cocktail consisting of 1000 mg of vitamin C, 600 IU of vitamin E, and 600 mg of ␣-lipoic acid. This study was performed in 87 healthy volunteers, pairing 42 younger volunteers (25 Ϯ 1 years) with 45 older volunteers (71 Ϯ 1 years). This was a double-blind, crossover, designed study. Blood velocity and brachial artery diameter, as measured with ultrasound imaging, were assessed before and after 5 minutes of forearm circulatory arrest. Serum markers of lipid peroxidation, total antioxidant capacity, endogenous antioxidant activity, vitamin C, plasma nitrite, nitrate, and 3-nitrotyrosine were also determined. With placebo, there was an agerelated reduction of brachial artery vasodilatation in young (7.4% Ϯ 0.6%) vs older (5.2% Ϯ 0.4%) patients. Antioxidant consumption improved flowmediated vasodilatation in older participants (placebo, 5.2% Ϯ 0.4%; antioxidant, 8.2% Ϯ 0.6%). Flow-mediated vasodilatation declined after antioxidant therapy in younger participants (placebo, 7.4% Ϯ 0.6%; antioxidant, 5.8% Ϯ 0.6%). Age was associated with a reduction in reactive hyperemia, but antioxidants did not alter the response in the younger or older groups.Comment: The data demonstrate that antioxidant consumption can acutely restore some elements of endothelial function in older patients. Antioxidants, however, apparently disrupt normal endothelial-dependent vasodilatation in younger individuals. The data must be rectified with clinical trials that have failed to demonstrate a beneficial effect of long-term antioxidant administration on cardiovascular health (Kris-Etherton PM et al, Circulation 2004;110:637-41). There are, however, certainly marked differences in study design between short-term interventional studies, such as in this report, and longer-term clinical trials of antioxidant therapy on cardiovascular health. The current study suggests some link between endothelial dysfunction and oxidative stress in older patients. The authors note the assay used in this study reflects peroxynitrite and that peroxynitrite may originate from multiple sources. The data cannot therefore be directly translated to imply potential benefits of long-term antioxidant therapy. Additional background work will be required before consideration of designing clinical trials evaluating the oral antioxidant cocktail used in this report.
Carbon nanotubes bound to tumor specific antibodies offer specific treatment for cancer cells without affecting surrounding tissue. The present study seeks to affirm the initial results of CNTs in cancer therapy by investigating the toxicological effect in mice injected with CNT-Ab followed by microwave hypothermia. We were particularly interested in evaluating the biodistribution, toxicity, and immune response that may be elicited from CNT-Ab exposure in mice. 4–5 week old mice (C57BL/6) were injected with various concentrations and combinations of multiwalled carbon nanotubes (MWCNT) conjugated with specific prostate-specific membrane antigen (PMSA) antibodies. After 1-week post-injection, mice were sacrificed followed by the collection of blood separated into serum, liver, kidney and other tissues for further analysis. Serum total protein concentration across the treatment groups was varied. No significant changes in albumin levels were detected when compared to the control group (No Treatment). Group YE (.125 mg/ml anti-PSMA-MWCNT + Microwave) was found to have consistently high blood serum analyte levels, indicating impaired liver and kidney function. Likewise, groups YB (Microwave only), YF [.5 mg/ml anti-PSMA-MWCNT (No Microwave)], and YG (.5 mg/ml plain MWCNT + Microwave) seemed to show indications of impaired liver function. Analysis of gene expression revealed a significant impact on the NF-KB inflammatory response pathway. NF-KB gene was up-regulated relative to controls in all treatment groups. These results seem to suggest marginal toxicity from the injection of CNT-Ab followed by microwave hyperthermia in mice subjects.
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