Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.

[Energy transfer between electric polymer PVK and terbium complex and its transmission electronmicroscope (TME) study].

A chloroform-soluble terbium complex, which is confirmed to be Tb(aspirin)3 phen using element analysis and FT-IR spectroscopy, was synthesized. Photoluminescent investigation on the terbium complex and PVK-terbium complex composite was conducted. Förster energy transfer occurred between the terbium complex and the PVK matrix. There are no overlap between UV spectrum of the complex and the emission spectrum of PVK, however, overlap is observed between the excitation spectrum of the complex and the emission spectrum of PVK. Therefore, we suggest that the necessary condition of Förster energy transfer should be overlap between the excitation (not UV) spectrum of one complex and the emission spectrum of polymer matrix. Further investigation indicates that the emission of PVK can be suppressed at different extents by doping various amount of Tb(aspirin)3 phen into PVK films. The ratio of Tb(aspirin)3 phen: PVK = 1:2 (wt%) are regarded as an optimized ratio for limiting the emission of PVK. TEM images of PVK/Tb(aspirin)3 phen films reveal that nanoparticles of the Tb complex are dispersed in the PVK matrix. The size of the aggregated complex in PVK matrix is 20-30 nm. The film is not homogeneous as dark regions co-exist with light region in the TEM images. This phenomenon may be related to the short lifetime of electroluminescent devices.

Active oxygen scavengers during cold acclimation of Scots pine seedlings in relation to freezing tolerance.

Freezing injury of plants may be caused by the deleterious reactions of active oxygen species, and free-radical scavenging systems may be important in the alleviation of freezing stress. To test the feasibility of this hypothesis, enzymes and metabolites that cooperatively scavenge O2 and H2O2 were analyzed in Scots pine (Pinus sylvestris L.) seedlings during a stepwise cold acclimation procedure. Elevated levels of enzymatic scavengers such as ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase were found, along with increased freezing tolerance during cold acclimation, supporting the hypothesis. Induction of the scavenging systems during acclimation is discussed in relation to freezing tolerance.