Selenoprotein P Modulates Methamphetamine Enhancement of Vesicular Dopamine Release in Mouse Nucleus Accumbens Via Dopamine D2 Receptors.

Dopamine (DA) transmission plays a critical role in processing rewarding and pleasurable stimuli. Increased synaptic DA release in the nucleus accumbens (NAc) is a central component of the physiological effects of drugs of abuse. The essential trace element selenium mitigates methamphetamine-induced neurotoxicity. Selenium can also alter DA production and turnover. However, studies have not directly addressed the role of selenium in DA neurotransmission. Selenoprotein P (SELENOP1) requires selenium for synthesis and transports selenium to the brain, in addition to performing other functions. We investigated whether SELENOP1 directly impacts (1) DA signaling and (2) the dopaminergic response to methamphetamine. We used fast-scan cyclic voltammetry to investigate DA transmission and the response to methamphetamine in NAc slices from C57/BL6J SELENOP1 KO mice. Recordings from SELENOP1 KO mouse slices revealed reduced levels of evoked DA release and slower DA uptake rates. Methamphetamine caused a dramatic increase in vesicular DA release in SELENOP1 KO mice not observed in wild-type controls. This elevated response was attenuated by SELENOP1 application through a selenium-independent mechanism involving SELENOP1-apolipoprotein E receptor 2 (ApoER2) interaction to promote dopamine D2 receptor (D2R) function. In wild-type mice, increased vesicular DA release in response to methamphetamine was revealed by blocking D2R activation, indicating that the receptor suppresses the methamphetamine-induced vesicular increase. Our data provide evidence of a direct physiological role for SELENOP1 in the dopaminergic response to methamphetamine and suggest a signaling role for the protein in DA transmission.

Management of oncological emergencies on the acute take.

In 2008, recommendations from the National Confidential Enquiry into Patient Outcome and Death identified large variations in the quality and safety of delivery of systemic anti-cancer therapy. In 49% of cases it was felt there was room for improvement and in 27% of cases treatment actually caused or hastened death. Every hospital with an emergency department and/or specialist oncology beds should therefore have a fully functioning acute oncology service to align acute oncology with urgent care. Many patients will still present via the acute take and therefore acute physicians need to be aware of the role of the acute oncology teams and management of oncology emergencies. This article discusses the role of the acute oncology team, management of acute oncology emergencies, namely neutropenic sepsis, metastatic spinal cord compression and superior vena cava obstruction, and important points for acute teams to consider.

Factors involved in treatment preference in patients with renal cancer: pazopanib versus sunitinib.

The last decade has seen a surge in the treatment options for metastatic renal cell carcinoma and life expectancies are now approaching 3 years from diagnosis. There is some suggestion that, for now at least, we may have reached a plateau in efficacy. Patients are often stable and on treatment for years rather than months. Attention has therefore shifted to a focus on patient preference rather than reported frequency of toxicities. The standard first-line treatment for metastatic clear-cell renal cancer is either sunitinib or pazopanib. The COMPARZ trial has shown that sunitinib and pazopanib have similar efficacy. The PISCES trial, with its unique design, has evaluated patient preference between pazopanib and sunitinib. This review explores the factors involved in treatment preference in patients with renal cancer and in particular the choice between pazopanib and sunitinib.