Anthony Barnett

Regulation of plasma ceramide levels with fatty acid oversupply : evidence that the liver detects and secretes de novo synthesised ceramide

Aims/hypothesisPlasma ceramide concentrations correlate with insulin sensitivity, inflammation and atherosclerotic risk. We hypothesised that plasma ceramide concentrations are increased in the presence of elevated fatty acid levels and are regulated by increased liver serine C-palmitoyltransferase (SPT) activity.MethodsLean humans and rats underwent an acute lipid infusion and plasma ceramide levels were determined. One group of lipid-infused rats was administered myriocin to inhibit SPT activity. Liver SPT activity was determined in lipid-infused rats, and obese, insulin resistant mice. The time and palmitate dose-dependent synthesis of intracellular and secreted ceramide was determined in HepG2 liver cells.ResultsPlasma ceramide levels were increased during lipid infusion in humans and rats, and in obese, insulin-resistant mice. The increase in plasma ceramide was not associated with changes in liver SPT activity, and inhibiting SPT activity by ∼50% did not alter plasma ceramide levels in lipid-infused rats. In HepG2 liver cells, palmitate incorporation into extracellular ceramide was both dose- and time-dependent, suggesting the liver cells rapidly secreted the newly synthesised ceramide.Conclusions/interpretationElevated systemic fatty acid availability increased plasma ceramide but this was not associated with changes in hepatic SPT activity, suggesting that liver ceramide synthesis is driven by substrate availability rather than increased SPT activity. This report also provides evidence that the liver is sensitive to the intracellular ceramide concentration, and an increase in liver ceramide secretion may help protect the liver from the deleterious effects of intracellular ceramide accumulation.

When the Brain Leaves the Scanner and Enters the Clinic: The Role of Neuroscientific Discourses in Producing the Problem of “Addiction”

Addiction neuroscience promises to uncover the neural basis of addiction by mapping changes in the “diseased brains” of people with “drug addictions.” It hopes to offer revolutionary treatments for addiction and reduce the stigma experienced by those seeking treatment for a medical, rather than moral, condition. While the promises of addiction neuroscience have received considerable attention, relatively few studies have examined how neuroscientific discourses and promises play out in drug treatment settings. Instead of asking how neuroscience might measure or treat a preexisting addiction “problem,” we draw on poststructuralist ideas to trace how neuroscientific discourses produce addiction as a certain type of “problem” and the effects of these particular problematizations. Based on interviews with a range of different types of treatment providers working in Victoria, Australia, we discuss three themes that reveal neuroscientific discourses at work: (1) constituting pathological subjects, (2) neuroplasticity and “recovery,” and (3) the alleviation of guilt and shame via references to the “diseased brain.” On the basis of our analysis, we argue that dominant neuroscientific discourses produce patients as pathologized subjects, requiring medical treatment. We also contend that the intersection of neuroscientific and recovery discourses enacts “recovery” in terms of brain “recovery” through references to neuroplasticity. Further, when neuroscientific and moral discourses intersect, addicted subjects are absolved from the guilt associated with immoral behavior emerging from a “hijacked brain.” We conclude by emphasizing the need for future critical work to explore the complex ways in which neuroscientific discourses operate in localized care ecologies.

Substance Use Terminology

quantity of reviews that would accurately relay the experience of care with that physician. Given the demand by consumers for information about physicians, other methods for publishing patient feedback are being developed,5 and some health systems are beginning to report quantitative reviews and narratives drawn from patient experience surveys.6 Because of the scarcity of reviews on commercial sites, one of these other methods of publishing patient feedback may emerge as the dominant route by which patients seek reviews about physicians. Methods that use systematic data collection (eg, surveys) may have a greater chance of amassing a sufficient quantity and quality of reviews to allow patients to make inferences about patient experience of care.

An Ethical Reevaluation: Where Are the Voices of Those With Anorexia Nervosa and Their Families?

The review by M€ uller and colleagues (2015) of published case studies of neurosurgical treatment of anorexia nervosa (AN) is generally sound. However, we believe that their, somewhat surprising, provisionally positive risk– benefit evaluation of deep brain stimulation (DBS) and ablative neurosurgery is unduly optimistic, and does not reflect the evidence presented. First, their review illustrates how few case reports have been published. As they note, these reports are likely to be subject to severe publication bias in which only positive case reports are published. The possible extent of this bias is exemplified in the textbook chapter that they cite (Sun et al. 2015) in which only four of 150 cases have been published in the peer-reviewed literature. Second, the scientific value of the data from these studies is doubtful. The procedures were conducted on patients who had not received treatments for which there is evidence of efficacy in AN. Outcome was assessed only by short-term monitoring of limited measures, primarily related to weight gain. There were limited data on depression and quality of life. Patient outcomes were assessed by the team conducting the surgical procedures, rather than by independent assessors. There was limited assessment of serious side effects. M€ uller and colleagues’ provisional overall judgment on the risks and benefits depends in part on the reports of Sun et al. (2015) that have not been subject to peer review. Third, very few of the case reports reviewed by M€ uller and colleagues met anything like the minimum ethical standards that they suggest for future trials of neurosurgical approaches to the treatment of AN. There are serious doubts about the extent to which consent has been informed and about whether the procedures have been treatments of last resort in intractable disorders: a standard approach for invasive experimental procedures such as neurosurgery. Fourth, M€ uller and colleagues give minimal attention to a number of important ethical considerations discussed in the treatment of addiction with DBS (Carter, Bell, Racine, and Hall 2011). Their positive assessment of the technology may increase patients’ expectation of benefit should they choose to undergo the intervention. Their assertion that the cause of a person’s disorder is due to