Arsenic is widely distributed in nature in the form of either metalloids or chemical compounds, which cause a variety of pathologic conditions including cutaneous and visceral malignancies. Recently, reactive oxygen species have been hypothesized to be one of the causes of arsenic-induced carcinogenesis. 8-Hydroxy-2'-deoxyguanosine is one of the major reactive oxygen species-induced DNA base-modified products that is widely accepted as a sensitive marker of oxidative DNA damage. We studied the presence of 8-hydroxy-2'-deoxyguanosine by immunohistochemistry using N45.1 monoclonal antibody in 28 cases of arsenic-related skin neoplasms and arsenic keratosis as well as in 11 cases of arsenic-unrelated Bowen's diseases. The frequency of 8-hydroxy-2'-deoxyguanosine positive cases was significantly higher in arsenic-related skin neoplasms (22 of 28; 78%) than in arsenic-unrelated Bowen's disease (one of 11; 9%) (p < 0.001 by chi2 test). 8-Hydroxy-2'-deoxyguanosine was also detected in normal tissue adjacent to the arsenic-related Bowen's disease lesions. Furthermore, arsenic was detected by neutron activation analysis in the deparaffined skin tumor samples of arsenic-related disease (four of five; 80%), whereas arsenic was not detected in control samples. Our results strongly suggest the involvement of reactive oxygen species in arsenic-induced human skin cancer. Key word: neutron activation analysis.

Registered nurses (RNs) and care workers (CWs) have important roles in providing end-of-life care to older adults, but little is known about the attitudes of RNs and CWs in Japan. In this study, 464 RNs and CWs working in facilities in Japan were asked to complete a self-administered questionnaire that included the Frommelt Attitude Toward Care of the Dying Scale, Form B, Japanese version (FATCOD-Form B-J) and the Death Attitude Profile (DAP), Japanese version. A total of 388 (83.6%) questionnaires were returned, and 367 (79.1%) were fully completed. The final sample included 190 RNs and 177 CWs. Multiple regression analysis showed that better attitudes toward caring for the dying were positively associated with seminar attendance and negatively associated with fear of death.

The SAR of 4-hydroxybenzaldehyde inhibitors of the trypanosome alternative oxidase (TAO), a critical enzyme for the respiration of bloodstream forms of trypanosomes, was investigated. Replacing the aldehyde group with a methyl ester resulted in a 10-fold increase in TAO inhibition and activity against . Remarkably, two analogues containing the 2-hydroxy-6-methyl scaffold ( and ) displayed single digit nanomolar TAO inhibition, which constitute the most potent 4-alkoxybenzoic acid derivatives described to date. was 50-times more potent against TAO and 10-times more active against compared to its benzaldehyde analogue. The farnesyl derivative was as potent a TAO inhibitor as ascofuranone with IC = 3.1 nM. Similar to ascofuranone derivatives, the 2-hydroxy and 6-methyl groups seemed essential for low nanomolar TAO inhibition of acid derivatives, suggesting analogous binding interactions with the TAO active site.

No abstract

The thermal rate constants for the reactions of electronically excited nitrogen atoms, N(2D) and N(2P), with C2H4 and C2D4 have been measured by using a pulse radiolysis−atomic absorption method between 225 and 292 K. From the results of the kinetic isotope effect for the N(2D) reaction, a main reaction mechanism was assigned to be the N addition to the double bond. This conclusion is in accordance with the prediction of our previous ab initio calculations. Variational transition-state theory calculations were performed for the N(2D) reaction by using the results of ab initio molecular orbital calculations. It was suggested that correction of the “multiple surface coefficient” is necessary to interpret the measured rate constants. The ratio of the rate constant of N(2D) to that of N(2P) was found to be close to unity and was much smaller than those for the reactions with H2 and CH4. The deactivation process of N(2P) was determined to be the spin-allowed quenching process, N(2P) + C2H4(S0) → N(4S) + C2H4(T1).