Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility Part 1

The reported selective serotonin Re-uptake Inhibitor Litoxetine was used as the starting point in the design of a range of potential SSRIs with high ease of synthetic accessibility. Preparation and subsequent optimization yielded a range of potent and highly selective SSRIs.     

Drosophila DBT Autophosphorylation of Its C-Terminal Domain Antagonized by SPAG and Involved in UV-Induced Apoptosis

Drosophila DBT and vertebrate CKIε/δ phosphorylate the period protein (PER) to produce circadian rhythms. While the C termini of these orthologs are not conserved in amino acid sequence, they inhibit activity and become autophosphorylated in the fly and vertebrate kinases. Here, sites of C-terminal autophosphorylation were identified by mass spectrometry and analysis of DBT truncations. Mutation of 6 serines and threonines in the C terminus (DBT^C/ala) prevented autophosphorylation-dependent DBT turnover and electrophoretic mobility shifts in S2 cells. Unlike the effect of autophosphorylation on CKIδ, DBT autophosphorylation in S2 cells did not reduce its in vitro activity. Moreover, overexpression of DBT^C/ala did not affect circadian behavior differently from wild-type DBT (DBT^WT), and neither exhibited daily electrophoretic mobility shifts, suggesting that DBT autophosphorylation is not required for clock function. While DBT^WT protected S2 cells and larvae from UV-induced apoptosis and was phosphorylated and degraded by the proteasome, DBT^C/ala did not protect and was not degraded. Finally, we show that the HSP-90 cochaperone spaghetti protein (SPAG) antagonizes DBT autophosphorylation in S2 cells. These results suggest that DBT autophosphorylation regulates cell death and suggest a potential mechanism by which the circadian clock might affect apoptosis.     

Suction lipoplasty: biohazardous aerosols and exhaust mist--the clouded issue

With the increased popularity of suction lipoplasty procedures, attention has been focused on their safety. One significant concern involves the rotary vane aspirators used to provide the suction required for the procedure. A series of experiments was carried out to determine whether aerosols are produced during the use of a rotary vane aspirator, since aerosols are known to be hazardous under appropriate conditions. Using a viable strain of Pseudomonas aeruginosa, we challenged the system through the suction port, and the exhaust from the aspirator was then cultured in a particle sampler. Results indicate that viable pathogens are released from the exhaust in physiologically significant particles capable of penetrating to the level of the alveolus in the normal human lung. These infectious particles were produced for 3 hours after the initial challenge. When an appropriate filtration device was attached to the aspirator outflow, the aspirator pump and environment were protected. In the absence of an appropriate filtration device, the aerosolized particles may constitute a hazard to patients or medical workers in the vicinity of the aspirator.