Photoactive dye-enhanced tissue ablation for endoscopic laser prostatectomy.

BACKGROUND AND OBJECTIVE: Laser light has been widely used as a surgical tool to treat benign prostate hyperplasia (BPH) over 20 years. Recently, application of high laser power up to 200 W was often reported to swiftly remove a large amount of prostatic tissue. The purpose of this study was to validate the feasibility of photoactive dye injection to enhance light absorption and eventually to facilitate tissue vaporization with low laser power. MATERIALS AND METHODS: Chicken breast tissue was selected as a target tissue due to minimal optical absorption at the visible wavelength. Four biocompatible photoactive dyes, including amaranth (AR), black dye (BD), hemoglobin powder (HP), and endoscopic marker (EM), were selected and tested in vitro with a customized 532 nm laser system with radiant exposure ranging from 0.9 to 3.9 J/cm(2) . Light absorbance and ablation threshold were measured with UV-Vis spectrometer and Probit analysis, respectively, and compared to feature the function of the injected dyes. Ablation performance with dye-injection was evaluated in light of radiant exposure, dye concentration, and number of injection. RESULTS: Higher light absorption by injected dyes led to lower ablation threshold as well as more efficient tissue removal in the order of AR, BD, HP, and EM. Regardless of the injected dyes, ablation efficiency principally increased with radiant exposure, dye concentration, and number of injection. Among the dyes, AR created the highest ablation rate of 44.2 ± 0.2 µm/pulse due to higher absorbance and lower ablation threshold. High aspect ratios up to 7.1 ± 0.4 entailed saturation behavior in the tissue ablation injected with AR and BD, possibly resulting from plume shielding and increased scattering due to coagulation. Preliminary tests on canine prostate with a hydraulic injection system demonstrated that 80 W with dye injection yielded comparable ablation efficiency to 120 W with no injection, indicating 33% reduced laser power with almost equivalent performance. CONCLUSION: Due to efficient coupling of optical energy, pre-injection of photoactive dyes promoted the degree of tissue removal during laser irradiation. Further studies will investigate spatial distribution of dyes and optimal injecting pressure to govern the extent of dye-assisted ablation in a predictable manner. In-depth comprehension on photoactive dye-enhanced tissue ablation can help accomplish efficient and safe laser vaporization for BPH with low power application.

DNA damage induced by red food dyes orally administered to pregnant and male mice.

We determined the genotoxicity of synthetic red tar dyes currently used as food color additives in many countries, including JAPAN: For the preliminary assessment, we treated groups of 4 pregnant mice (gestational day 11) once orally at the limit dose (2000 mg/kg) of amaranth (food red No. 2), allura red (food red No. 40), or acid red (food red No. 106), and we sampled brain, lung, liver, kidney, glandular stomach, colon, urinary bladder, and embryo 3, 6, and 24 h after treatment. We used the comet (alkaline single cell gel electrophoresis) assay to measure DNA damage. The assay was positive in the colon 3 h after the administration of amaranth and allura red and weakly positive in the lung 6 h after the administration of amaranth. Acid red did not induce DNA damage in any sample at any sampling time. None of the dyes damaged DNA in other organs or the embryo. We then tested male mice with amaranth, allura red, and a related color additive, new coccine (food red No. 18). The 3 dyes induced DNA damage in the colon starting at 10 mg/kg. Twenty ml/kg of soaking liquid from commercial red ginger pickles, which contained 6.5 mg/10 ml of new coccine, induced DNA damage in colon, glandular stomach, and bladder. The potencies were compared to those of other rodent carcinogens. The rodent hepatocarcinogen p-dimethylaminoazobenzene induced colon DNA damage at 1 mg/kg, whereas it damaged liver DNA only at 500 mg/kg. Although 1 mg/kg of N-nitrosodimethylamine induced DNA damage in liver and bladder, it did not induce colon DNA damage. N-nitrosodiethylamine at 14 mg/kg did not induce DNA damage in any organs examined. Because the 3 azo additives we examined induced colon DNA damage at a very low dose, more extensive assessment of azo additives is warranted.

Reproductive and neurobehavioral effects of amaranth administered to mice in drinking water.

The color additive amaranth was given in the drinking water at levels of 0 (control), 0.025, 0.075, and 0.225% from 5 weeks of age in F0 generation until F1 generation mice were weaned, with selected reproductive, developmental and behavioral parameters being measured. Amaranth had little adverse effect upon litter size, litter weight and sex ratio. Average body weight in both sexes of the F1 mice was significantly increased in the 0.025% group in both sexes. Survival index at postnatal day (PND) 21 was reduced in the 0.025% amaranth group. For the neurobehavioral parameters, surface righting at PND 4 in female offspring and olfactory orientation in both sexes were significantly affected by treatment. Several parameters of movement activity of male offspring at 3 weeks of age were affected in amaranth 0.075% group, but those of female offspring were similar in all groups. The dose levels of amaranth in this study produced a little adverse effect on behavioral development in mice.

Effect of feeding amaranth (food red no. 2) on the jejunal sucrase and digestion-absorption capacity of the jejunum in rats.

To clarify the effect of feeding 5% amaranth (Food Red No. 2, Am) alone or with 5% dietary fiber on jejunal mucosal integrity, change in jejunal sucrase activity before and after the feeding was compared between rats fed and fasted previously. Digestion-absorption capacity of the jejunum was also examined by perfusing 15 mmol/liter sucrose and 30 mmol/liter glycylglycine through the anesthetized rat jejunum after 14 days of feeding Am. Gobo dietary fiber (GDF) was prepared from the roots of edible burdock (Arctium lappa L.). At the end of 3 days' fasting, rats had 20% less body weight, 30% less mucosal protein and 50% less jejunal sucrase activity per unit length than those before fasting. Although rats fed Am showed severe diarrhea and growth retardation as observed in previous reports, initial sucrase level was not changed by feeding Am for 3 days even in the fasted rats. When sucrase activity on day 3 after feeding was compared among inter-groups, however, rats fed Am showed sucrase activity lower than that of rats fed either the basal diet or the basal diet containing Am plus GDF only when they had been fasted previously. After 14 days of feeding, rats fed Am after 3 days' fasting regained sucrase activity up to that of rats fed the basal diet despite the remarkable growth retardation. Jejunal perfusion in situ showed that digestion-absorption capacity for sucrose and glycylglycine in rats fed 5% Am for 14 days was also the same as that in rats fed the basal diet. These results suggest that feeding Am can reduce neither jejunal sucrase nor digestion-absorption capacity of epithelial cells of the jejunum, but retards the regain of the lowered sucrase level at earlier stage of feeding when rats have been fasted before the feeding, and that concurrent feeding of GDF promotes catch-up of the sucrase level lowered by the fasting.

Mechanisms of adverse effect of amaranth feeding in the rat.

In order to clarify the mechanism of the adverse effects of dietary amaranth, trisodium 1-(4-sulfo-1-naphthylazo)-2-naphthyl-3,6 disulfonic acid, the effects of amaranth in vitro and in a jejunum perfusion in vivo on intestinal sucrase were investigated in rats. The inhibitory effect of amaranth in vitro on the sucrase activity was not detected even at the concentration of 1%, whereas the remarkable release of intestinal sucrase from intestine was observed with the jejunum perfusion of Ringer bicarbonate solution (RBS) containing amaranth at the 1% level. On the other hand, the perfusion of RBS containing tris(hydroxymethyl)-aminomethane, a strong inhibitor of intestinal disaccharidase activities, did not produce the release of intestinal alkaline phosphatase. These findings suggest that the toxicity of dietary amaranth is due to the exfoliating or solubilizing effects of amaranth on the brush border membrane of the small intestine.

Teratological evaluation of FD&C red no.2-a collaborative government-industry study. I Introduction, experimental materials, and procedures.

Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red. No 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD*C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.