A review of rectal toxicity following permanent low dose-rate prostate brachytherapy and the potential value of biodegradable rectal spacers.

Permanent radioactive seed implantation provides highly effective treatment for prostate cancer that typically includes multidisciplinary collaboration between urologists and radiation oncologists. Low dose-rate (LDR) prostate brachytherapy offers excellent tumor control rates and has equivalent rates of rectal toxicity when compared with external beam radiotherapy. Owing to its proximity to the anterior rectal wall, a small portion of the rectum is often exposed to high doses of ionizing radiation from this procedure. Although rare, some patients develop transfusion-dependent rectal bleeding, ulcers or fistulas. These complications occasionally require permanent colostomy and thus can significantly impact a patient's quality of life. Aside from proper technique, a promising strategy has emerged that can help avoid these complications. By injecting biodegradable materials behind Denonviller's fascia, brachytherpists can increase the distance between the rectum and the radioactive sources to significantly decrease the rectal dose. This review summarizes the progress in this area and its applicability for use in combination with permanent LDR brachytherapy.

The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells.

A direct correlation has been reported between the severity of symptoms associated with rhinovirus infection and the concentration of interleukin-8 in nasal secretions. The purpose of these studies was to examine the mechanism of rhinovirus-induced IL-8 elaboration. Rhinovirus infection induced oxidative stress in Beas-2b cells and the concentration of H2O2 in supernatant media from rhinovirus challenged cells was 12.5 +/- 6.1 microM 1 h after challenge compared to 0.7 +/- 0.3 microM in supernatant from control cells. N-acetyl cysteine inhibited RV-induced NF-kappaB activation and IL-8 elaboration. IL-8 concentrations were 36 +/- 2 pg/ml and 10 +/- 1 pg/ml 6 h after virus challenge in untreated and NAC-treated (30 mM NAC) cells, respectively. Despite the effects of NAC on IL-8 elaboration and NF-kappaB activation, RV stimulated increases in supernatant H2O2 were not altered by NAC. These data suggest that RV stimulation of IL-8 in respiratory epithelium is mediated through production of oxidative species and the subsequent activation of NF-kappaB.

Rhinovirus-induced oxidative stress and interleukin-8 elaboration involves p47-phox but is independent of attachment to intercellular adhesion molecule-1 and viral replication.

Virus-induced elaboration of proinflammatory cytokines is mediated by virus-induced oxidative stress. The purpose of these studies was to determine the source of the virus-induced oxidative stress. Inhibition of viral replication with antibody to intercellular adhesion molecule-1 had no effect on virus-induced oxidative stress or interleukin-8 (IL-8) response (597+/-88 vs. 668+/-78 pg/mL in control cells). Treatment of cells with diphenylene iodonium inhibited virus-induced oxidative stress and IL-8 elaboration, but allopurinol, ibuprofen, and rotenone had no effect. Studies in cell lines produced from a patient with gp91-phox deficiency revealed normal responses. In contrast, the oxidative response was decreased and the IL-8 concentration was 227+/-36 pg/mL in cells from a patient with p47-phox deficiency, compared with 664+/-48 pg/mL in control cells. These studies suggest that the stimulation of reactive oxygen species by viral challenge occurs at the cell surface even in the absence of viral replication and involves a flavoprotein that may act in concert with p47-phox.