Platelet inhibitory effects of the Phase 3 anticancer and normal tissue cytoprotective agent, RRx-001.

The platelet inhibitory effects of the Phase 3 anticancer agent and nitric oxide (NO) donor, RRx-001, (1-bromoacetyl-3,3-dinitroazetidine) were examined ex vivo and compared with the diazeniumdiolate NO donor, diethylenetriamine NONOate (DETA-NONOate), which spontaneously releases nitric oxide in aqueous solution. In the absence of red blood cells and in a dose-dependent manner, DETA-NONOate strongly inhibited platelet aggregation induced by several stimuli (ADP, epinephrine and collagen) whereas RRx-001 only slightly inhibited platelet aggregation under the same conditions in a dose-dependent manner; these antiaggregant effects were blocked when both DETA-NONOate and RRx-001 were co-incubated with carboxy-PTIO (CPTIO 0.01-100 micromol), a widely accepted NO scavenger. However, in the presence of red blood cells from healthy human donors, RRx-001, which binds covalently to haemoglobin (Hb) and catalyses the production of NO from endogenous nitrite, more strongly inhibited the aggregation of platelets than DETA-NONOate in a dose-dependent manner likely because haemoglobin avidly scavenges nitric oxide and reduces its half-life; the RRx-001-mediated platelet inhibitory effect was increased in the presence of nitrite. The results of this study suggest that RRx-001-bound Hb (within RBCs) plays an important role in the bioconversion of NO2- to NO. , which makes RRx-001 a more physiologically relevant inhibitor of platelet aggregation than other nitric oxide donors, whose effects are attenuated in the presence of red blood cells. Therefore, RRx-001-mediated platelet inhibition is a potentially useful therapeutic property, especially in hypercoagulable cancer patients that are at an increased risk of thrombotic complications

Examining Librarians’ Rights in the Philippine Copyright Law: The Academic Law Librarians\u27 Standpoint

Academic law librarians have two primary responsibilities in the profession: to be faithful to the fundamental law of library science, and to be the frontrunners in implementing the law of the land. The Philippine copyright law tests the academic law librarians\u27 purpose in accomplishing both responsibilities. In this pandemic, when most library services are on online modality, the academic law librarians’ duty of providing information the fastest way possible may slow down due to their obligation to abide by the copyright law. To avoid this scenario and provide recommendations when this happens, the researchers of this study examines the overall perception of academic law librarians on the following: (1) the degree of which the copyright law in the country affects the librarians\u27 provision of information service in this time of online modality; (2) the copyright law’s impacts in fulfilling librarians\u27 mission of carrying out the first fundamental law of library science; and (3) the extent of support the copyright law is providing the librarians while performing their tasks. Results are gathered using a 3-part survey questionnaire that tackles the demographics, perceptions, and concerns, and suggestions of the respondents. These are analyzed using percentages, weighted mean, and Spearman’s Rank Correlation Coefficient. Salient results such as the low level of support the academic law librarians perceive they can get from the Philippine copyright law, and their conviction that the prevailing law needs additional provisions to protect librarians in providing information services while adhering to the fundamental law of librarianship, are significantly discussed in this study