'Special K' and a loss of cell-to-cell adhesion in proximal tubule-derived epithelial cells: modulation of the adherens junction complex by ketamine

Ketamine, a mild hallucinogenic class C drug, is the fastest growing ‘party drug’ used by 16–24 year olds in the UK. As the recreational use of Ketamine increases we are beginning to see the signs of major renal and bladder complications. To date however, we know nothing of a role for Ketamine in modulating both structure and function of the human renal proximal tubule. In the current study we have used an established model cell line for human epithelial cells of the proximal tubule (HK2) to demonstrate that Ketamine evokes early changes in expression of proteins central to the adherens junction complex. Furthermore we use AFM single-cell force spectroscopy to assess if these changes functionally uncouple cells of the proximal tubule ahead of any overt loss in epithelial cell function. Our data suggests that Ketamine (24–48 hrs) produces gross changes in cell morphology and cytoskeletal architecture towards a fibrotic phenotype. These physical changes matched the concentration-dependent (0.1–1 mg/mL) cytotoxic effect of Ketamine and reflect a loss in expression of the key adherens junction proteins epithelial (E)- and neural (N)-cadherin and β-catenin. Down-regulation of protein expression does not involve the pro-fibrotic cytokine TGFβ, nor is it regulated by the usual increase in expression of Slug or Snail, the transcriptional regulators for E-cadherin. However, the loss in E-cadherin can be partially rescued pharmacologically by blocking p38 MAPK using SB203580. These data provide compelling evidence that Ketamine alters epithelial cell-to-cell adhesion and cell-coupling in the proximal kidney via a non-classical pro-fibrotic mechanism and the data provides the first indication that this illicit substance can have major implications on renal function. Understanding Ketamine-induced renal pathology may identify targets for future therapeutic intervention

Effects of stellar collisions on star cluster evolution and core collapse

We systematically study the effects of collisions on the overall dynamical evolution of dense star clusters using Monte Carlo simulations over many relaxation times. We derive many observable properties of these clusters, including their core radii and the radial distribution of collision products. We also study different aspects of collisions in a cluster taking into account the shorter lifetimes of more massive stars, which has not been studied in detail before. Depending on the lifetimes of the significantly more massive collision products, observable properties of the cluster can be modified qualitatively; for example, even without binaries, core collapse can sometimes be avoided simply because of stellar collisions.Comment: 5 pages, 4 figures, Submitted for the IAU symposium, 246 in Capri, Ital

Barnett Says Delay Degree To Meredith

Governor Ross Barnett claims that the awarding of James Meredith\u27s degree should be deferred pending an investigation that Meredith violated a directive given to students to refrain from giving press releases or public statements; Source: Clarion-Ledger (Jackson, Miss.)https://egrove.olemiss.edu/jws_clip/1128/thumbnail.jp

Affairs of State: Rebel Underground

Column written in support of the Rebel Underground, a pro-segregation underground newspaper published at the University of Mississippi and Millsaps College; Source: Clarion-Ledger (Jackson, Miss.)https://egrove.olemiss.edu/jws_clip/1067/thumbnail.jp

Affairs of State

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Gov. Barnett On National Radio Circuit

Article describing Governor Ross Barnett\u27s radio broadcast, in which he told a nationwide audience about economic and industrial progress being made in the state of Mississippi; Source: Clarion-Ledger (Jackson, Miss.)https://egrove.olemiss.edu/jws_clip/1324/thumbnail.jp