Resonant spectra of highly charged ions are evaluated numerically in the presence of super intense high-frequency laser pulses up to 1022W/cm2. The associated field strengths are still small compared to those inherent in highly charged ions, restricting us to the relativistic multiphoton regime. We predict the emission of hard X-ray radiation due to near-resonant multiphoton interaction with clear relativistic signatures for the one-electron ions Xe53+ and U91+.
Controlled-release formulations of atypical antipsychotics have recently been introduced into clinical practice. Clinical studies have indicated that these new therapies induce meaningful improvements in the functioning and quality of life of schizophrenic individuals.The present analysis makes an attempt to address the clinical relevance of these studies and their contribution to the understanding of the mechanisms of action of these new drugs. A Medline search was done using the keywords 'antipsychotic', 'plasma level', 'quality of life' and 'functioning'.After reviewing the literature, it seems that symptom control and side effects may play a role in modulating the functioning and quality of life of schizophrenic individuals treated with controlled-release formulations of atypical antipsychotics. The analysis also highlights that these new drugs may possess peculiarities and similarities in regulating patient functioning. However, the low number of clinical analyses that have focused on these aspects of antipsychotic therapy limits the interpretation of the results. Additional comparative clinical trials are needed to evaluate how the pharmacokinetic/pharmacodynamic properties of antipsychotic drugs may modulate the functioning and quality of life of schizophrenic individuals, as well as to establish whether new clinical benefits may come from the use of these drugs in schizophrenia therapy.
The search for new disease-modifying drugs for Parkinson's disease is a slow and highly expensive process, and the repurposing of drugs already approved for different medical indications is becoming a compelling alternative option for researchers. Genetic variables represent a predisposing factor to the disease and mutations in Leucine-rich repeat kinase 2 (LRRK2) locus have been correlated to late-onset autosomal-dominant PD. The common fruit fly Drosophila melanogaster carrying the mutation LRRK2 loss-of-function in the WD40 domain (LRRK2WD40), is a simple in vivo model of PD and is a valid tool to first evaluate novel therapeutic approaches to the disease. Recent studies have suggested a neuroprotective activity of immunomodulatory agents in PD models. Here the immunomodulatory drug Pomalidomide (POM), a Thalidomide derivative, was examined for the first time in the drosophila LRRK2WD40 genetic model of PD. Mutant and wild type flies received increasing POM doses (1, 0.5, 0.25 mM) through their diet from day 1 post eclosion, until post-natal day (PN) 7 or 14, when POM's actions were evaluated by quantifying changes in climbing behavior as a measure of motor performance, the number of brain dopaminergic neurons and mitochondria integrity. LRRK2WD40 flies displayed a spontaneous age-related impairment of climbing activity, and POM significantly and dose-dependently improved climbing performance both at PN 7 and PN 14. LRRK2WD40 fly motor disability was underpinned by a progressive loss of dopaminergic neurons in posterior clusters of the protocerebrum, which are involved in the control of locomotion, and by a low number of T-bars density in the presynaptic bouton active zones. POM treatment fully rescued the cell loss in all posterior clusters at PN 7 and PN 14, and significantly increased the T-bars density. Moreover, several damaged mitochondria with dilated cristae were observed in LRRK2WD40 flies treated with vehicle but not following POM. This study demonstrates, for the first time, the neuroprotective activity of the immunomodulatory agent POM in a genetic model of PD. POM is an FDA-approved clinically available and well tolerated drug used for the treatment of multiple myeloma. If further validated in mammalian models of PD, POM could rapidly be clinically tested in humans.
