Zhang et al. (Research Articles, 13 March 2009, p. 1448) reported that synaptic vesicles usually release neurotransmitter through a kiss-and-run mechanism occurring within 1 second but that full collapse of the vesicles becomes more prevalent with repeated stimuli. We report that the kinetics of vesicle retrieval do not change during a stimulus train, with endocytosis occurring in 10 to 15 seconds.
Clofarabine, a next-generation deoxyadenosine analogue, was developed on the basis of experience with cladribine and fludarabine in order to achieve higher efficacy and avoid extramedullary toxicity. During the past decade this is the only drug granted approval for treatment of pediatric acute leukemia. Recent clinical studies have established the efficacy of clofarabine in treating malignancies with a poor prognosis, such as adult, elderly, and relapsed pediatric leukemia. The mechanisms of its anti-cancer activity involve a combination of direct inhibition of DNA synthesis and ribonucleotide reductase and induction of apoptosis. Due to this broad cytotoxicity, this drug is effective against various subtypes of leukemia and is currently being tested as an oral formulation and for combination therapy of both leukemias and solid tumors. In this review we summarize current knowledge pertaining to the molecular mechanisms of action and pharmacological properties of clofarabine, as well as clinical experiences with this drug with the purpose of facilitating the evaluation of its efficacy and the development of future therapies.
In this commentary, we discuss the implications of the findings by Berger, Hohl, and Casper (this issue) together with the emerging database on the effects of Internet treatment for social anxiety disorder (social phobia). Their article is the third independent replication of guided Internet treatment of social anxiety disorder, and in this article, we comment on future research challenges and if Internet treatment now can be regarded as ready for dissemination into regular clinical settings.