Investigations on organ-specific metabolism and genotoxic effects of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine (BCPN) and its analogs N-nitrosodibutylamine (NDBA) and N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA)

N-Nitrosodibutylamine (NDBA) and its omega-oxidized metabolites N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA) and N-nitrosobutyl-3-carboxypropylamine (BCPN) are potent urinary bladder carcinogens. To study putative organ specific activation of BCPN, its alpha-oxidation by liver and urinary bladder microsomal fractions was investigated in comparison to NDBA and 4-OH-NDBA. Additionally, induction of DNA single strand breaks (SSB) was monitored in hepatocytes and in a human lymphoblastoid cell line (Namalva) in the presence and absence of external metabolic activation, including N-nitroso-t-butyl-n-butylamine as a negative control. BCPN was alpha-hydroxylated and dealkylated at both alkyl chains in small rates (about 1 nmol x mg protein-1 x 60 min-1) by microsomes from rat liver and pig urinary bladder epithelium. NDBA and 4-OH-NDBA were dealkylated at similarly low rates by pig urinary bladder microsomes, in strong contrast to the high debutylation rates observed for rat liver microsomes. Correspondingly, SSB induction by NDBA and 4-OH-NDBA was observed in Namalva cells with NDBA and 4-OH-NDBA in the presence of PB-induced rat liver microsomes but not with urinary bladder microsomes or without external activation. BCPN did not induce DNA-damage in Namalva cells (with or without external activation) or in rat hepatocytes. Significant induction of sister chromatid exchanges (SCEs) and micronuclei, however, was observed in Namalva cells after incubation with NDBA and BCPN. Our data suggest activation of BCPN via alpha-oxidation in the urinary bladder, even though activation rate in-vitro is so low that a positive response is not detectable by several short-term tests.     

Plasma tenoxicam concentrations after single and multiple oral doses

The pharmacokinetics of single- and multiple-dose administration of tenoxicam 20 mg were evaluated in 8 healthy males. Maximum plasma concentration (Cmax) after the first dose was 2.76 +/- 0.48 micrograms/ml (mean +/- s.d.) and the time to reach Cmax (Tmax) was 5.0 +/- 3.0 h. The area under the plasma concentration-time curve (AUC0-infinity) after a single administration of tenoxicam was 242.5 +/- 73.5 micrograms x h/ml. The elimination half-life (t1/2) was 66.3 +/- 15.8 h and the plasma concentration at 24 hours after dosing (Cmin) was 1.84 +/- 0.33 micrograms/ml. Steady-state plasma concentrations of tenoxicam were virtually reached after 10 consecutive daily doses. At steady-state, Cmax averaged 13.63 +/- 3.33 micrograms/ml and Tmax remained 5.0 +/- 3.0 hours. AUC within a dosing interval at steady-state was 262.2 +/- 67.0 micrograms x h/ml, Cminss was 9.67 +/- 3.25 micrograms/ml, and t1/2 averaged 74.2 +/- 13.3 h. The average fluctuation during multiple-dose administration was 26.8 +/- 8.0% and the accumulation ratio was 5.82 +/- 0.60. Steady-state pharmacokinetic parameters predicted from the first-dose data slightly underestimated observed values, but the results supported the assumption of linear pharmacokinetics during multiple-dose tenoxicam administration.     

Advances in light curing units and curing techniques: a literature review.

There exists a constant need for a dental curing light that works reliably and conveniently in the general practitioner's office and can be used effectively for all the different curing procedures. Due to the need for improved physical properties of resin based composites (RBCs) and less stress at the marginal interface, light curing units (LCUs) experienced significant advances in the past years. The dental industry has focused on reducing the curing time by developing higher intensity curing lights and by altering the resin composition and photo-initiator concentration. As a result the dentist can now choose from a vast variety of curing lights, light intensities and curing methods. This article presents a review of the advances in light curing units and curing techniques, as well as the scientific principles that guided past developments and that will influence future advances.     

Implementing a simpler approach to mission-based planning in a medical school.

Changes in the education, research, and health care environments have had a major impact on the way in which medical schools fulfill their missions, and mission-based management approaches have been suggested to link the financial information of mission costs and revenues with measures of mission activity and productivity. The authors describe a simpler system, termed Mission-Aligned Planning (MAP), and its development and implementation, during fiscal years 2002 and 2003, at the School of Medicine at the University of Texas Health Science Center at San Antonio, Texas. The MAP system merges financial measures and activity measures to allow a broad understanding of the mission activities, to facilitate strategic planning at the school and departmental levels. During the two fiscal years mentioned above, faculty of the school of medicine reported their annual hours spent in the four missions of teaching, research, clinical care, and administration and service in a survey designed by the faculty. A financial profit or loss in each mission was determined for each department by allocation of all departmental expenses and revenues to each mission. Faculty expenses (and related expenses) were allocated to the missions based on the percentage of faculty effort in each mission. This information was correlated with objective measures of mission activities. The assessment of activity allowed a better understanding of the real costs of mission activities by linking salary costs, assumed to be related to faculty time, to the missions. This was a basis for strategic planning and for allocation of institutional resources.