Other sequences corresponding to potential pathogenicity factors
were identified in the highly aggressive isolate. This work indicates that, in combination with functional genomics, proteomics-based analyses can provide additional insights into pathogenesis and potential management strategies for this disease.”
“Evidence suggests that depression is associated with an increase in the high-affinity conformation of the alpha 2-adrenoceptors in human brain. Such enhanced alpha 2-adrenoceptor activity could explain the deficit in central noradrenergic transmission described in the aetiology of depression. Thus, administration Angiogenesis inhibitor of alpha 2-adrenoceptor antagonists augments noradrenaline levels and provides an effective therapeutic approach for the treatment of depressive disorders.
In previous studies, we have characterized three new synthesized guanidine and 2-aminoimidazoline aromatic derivatives (8b, 17b and 20b) as alpha 2-adrenoceptor antagonists that
are able to increase extracellular concentration of noradrenaline in rat brain.
The purpose of the present study was to evaluate the in vivo antidepressant-like properties of these three new alpha 2-adrenoceptor antagonists. For that aim, compounds were tested on the tail suspension test (TST) and forced swim test (FST), two classically widely-used behavioural paradigms for the evaluation of antidepressant-like activity. Compound 8b significantly reduced the immobility time at 10, 20 and Evofosfamide clinical trial 40 mg/kg doses in both TST and FST. Compound 17b reduced the immobility time at 40 mg/kg in both Captisol in vitro TST and FST. Compound 20b showed a significant decrease in the immobility time at 20 mg/kg in the TST. As drugs of reference, fluoxetine induced a significant
antidepressant-like effect in both TST and FST, while mirtazapine induced a significant antidepressant-like effect only in the FST. Additionally, none of the tested compounds increased locomotor activity or displayed anxiolytic-like properties.
These results suggest that these new synthesized alpha 2-adrenoceptor antagonists may be useful as potential antidepressant drugs. (C) 2012 Elsevier Ltd. All rights reserved.”
“The screening for treatment-induced enzyme activities offers the opportunity to discover important regulatory mechanisms and the identification of potential targets for anti-cancer therapies. A novel screening technique was applied to screen substrate peptide sequences for proteolytic activities up- or down-regulated by ionizing radiation in tumor cells. One specific substrate sequence was cleaved in control cell extracts but to a smaller extent in irradiated cell extracts and investigated in detail. Based on protease-class-specific inhibitory studies and cleavage site analysis a potent warhead-inhibitor was synthesized and used to identify the proteasome as the protease of interest.