Prevention of urinary bladder cancer in the FHIT knock-out mouse with Rofecoxib, a Cox-2 inhibitor.

OBJECTIVES: Aberrant or increased expression of cyclooxygenase-2 (COX-2) has been implicated in the pathogenesis of many diseases, including cancer. However, the exact mechanism by which COX-2 may influence tumorigenesis has yet to be described. To investigate the chemopreventive role of a COX-2 inhibitor, rofecoxib, in the development of urinary bladder cancer, we studied the effect of this drug in heterozygous and nullizygous fragile histidine triad (FHIT) gene-deficient mice in a chemically induced carcinogenesis model. MATERIALS AND METHODS: Two-hundred eight mice consisting of 50 FHIT +/+, 63 FHIT +/- and 95 FHIT -/-, were divided into five treatment groups and followed up for 15 weeks. Mice were treated with freshly prepared solution of 0.1% or 0.01% N-butyl-N-(-4-hydroxybutyl)-nitrosamine (BBN) in their drinking water and rofecoxib was administered in mouse chow at 150 parts per million concentration. Mice were sacrificed, and accurate histological analysis of the bladder was performed. RESULTS: Rofecoxib treatment significantly reduced the incidence of preneoplastic lesions/bladder tumors (P = 0.016). Comparing the incidence of neoplastic lesions in mice treated with rofecoxib and BBN (22/56, 39.3%) and mice treated only with BBN (32/57, 56.1%), a protective role of rofecoxib on the BBN tumor induction has been observed (P = 0.024). A similar result (P = 0.002) has been reached observing the incidence of mild and moderate dysplasia in mice treated with a lower concentration of BBN (8/16, 50.0% vs. 20/24, 83.3%).Moreover, as previously observed, a significant increase in neoplastic lesions in the FHIT +/- and FHIT -/- vs. FHIT +/+ mice after BBN treatment has been observed (P = 0.003). CONCLUSIONS: These findings suggest that rofecoxib provides a therapeutic defense against bladder carcinogenesis in our model and confirmed that the FHIT knock-out mouse is a suitable system to study in vivo bladder carcinogenesis.

Determination of methyl isothiocyanate in air downwind of fields treated with metam-sodium by subsurface drip irrigation.

Air concentrations of methyl isothiocyanate (MITC) were determined near two fields treated with metam-sodium (MS) by subsurface drip irrigation. The two study fields showed measurable airborne MITC residues during application of MS and for periods up to 48 h postapplication. Using a Gaussian plume dispersion model, flux values were estimated for all of the sampling periods. On the basis of the flux estimates, the amount of MITC that volatilized within the 48 h period was about 1.4% of the applied material. Compared to other studies, MITC residues in air measured during application by subsurface drip irrigation were up to four orders-of-magnitude lower than those previously published for applications involving delivery through surface irrigation water. Our measured concentrations of MITC in field air were at levels below current regulatory guidance and thresholds for adverse human health effects.

Effectiveness of high-frequency holmium:YAG laser stone fragmentation: the "popcorn effect".

PURPOSE: To demonstrate the validity of non-contact holmium:yttrium-aluminum-garnet laser stone fragmentation in an in-vitro model and to characterize the optimal laser settings to perform this technique. MATERIALS AND METHODS: A caliceal model consisting of a glass test tube filled with 0.9% normal saline was created. Into this system, a 365-mum laser fiber was inserted after stabilization 2 mm above the surface of the stones. Laser experiments were conducted using tubes that contained four soda limestone phantoms with a total stone burden of approximately 0.2 g per tube. The laser energy was varied between 1.0 and 1.5 J, with a firing frequency of 20, 30, or 40 Hz. Ten tubes were tested at each setting combination for a duration of 2 minutes. Thus, 60 tubes were tested. The contents of each tube were filtered through a 2-mm sieve after treatment, and all remaining fragments were dried for 5 days. The fragments were weighed, and the difference from pretreatment was calculated. Differences in weights and laser settings were compared using one-tailed and two-sample t testing. RESULTS: Each experiment resulted in a significant decrease in stone burden from prelaser weight (all P values = 0.00). Laser settings were manipulated between combinations of 1.0 J at a frequency of 20, 30, and 40 Hz, and an energy of 1.5 J and 20, 30, and 40 Hz. This resulted in a respective mean weight loss of -42%, -58%, and -47% at 1.0 J, and -24%, -56%, and -63% at 1.5 J. The t tests were performed to detect differences between weight loss and to determine the optimal settings. Laser settings of 1.5 J and 40 Hz for 2 minutes produced the greatest mean decrease in stone burden (63%). This loss was significantly different from that of all settings at 1.0 J and the setting of 1.5 and 20 Hz (P < 0.05). The mean percentage weight loss for each setting was then normalized to the total energy used. Settings of 1.0 J and 20 Hz were the most efficient, with a change in weight of -18% per kJ. CONCLUSIONS: We duplicated the "popcorn effect" of non-contact laser use in vitro. In this model, the technique results in a significant decrease in stone burden (up to 63%) in just 2 minutes. Adequate energy and high frequency seemed to optimize the effectiveness of the method, but excessive energy and frequency produced diminishing returns.