James Allen

Cocaine and human immunodeficiency virus type 1 gp120 mediate neurotoxicity through overlapping signaling pathways.

Although it has been well documented that drugs of abuse such as cocaine cause enhanced progression of human immunodeficiency virus (HIV)-associated neuropathological disorders, the underlying mechanisms mediating these effects remain poorly understood. The present study demonstrated that exposure of rat primary neurons to both cocaine and gp120 resulted in increased cell toxicity compared to cells treated with either factor alone. The combinatorial toxicity of cocaine and gp120 was accompanied by an increase in both caspase-3 activity and expression of the proapoptotic protein Bax. Furthermore, increased neurotoxicity in the presence of both the agents was associated with a concomitant increase in the production of intracellular reactive oxygen species and loss of mitochondrial membrane potential. Increased neurotoxicity mediated by cocaine and gp120 was ameliorated by NADPH oxidase inhibitor apocynin, thus underscoring the role of oxidative stress in this cooperation. Signaling pathways including c-jun N-teminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK)/ mitogen-activated protein kinases (MAPK), and nuclear factor (NF)-κB were also identified to be critical in the neurotoxicity induced by cocaine and gp120. These findings thus underscore the role of oxidative stress, mitochondrial and MAPK signal pathways in cocaine and HIV gp120-mediated neurotoxicity.

Management of Barrett's esophagus with low-grade dysplasia

Barretts esophagus progresses to esophageal adenocarcinoma in a stepwise histological fashion of no dysplasia, low grade dysplasia, high grade dysplasia and cancer. Hence the progression to cancer from various histological stages is different. Progression to cancer from low grade dysplasia is highly variable in the literature due to high inter-observer variability between pathologists in diagnosing it. Studies have shown the utility of having confirmation of low grade dysplasia by expert pathologists or documenting its persistence on two subsequent endoscopies in order to unify the diagnosis. The treatment of low grade dysplasia is variable. In this article we summarize the diagnosis, evaluation and management of low grade dysplasia in Barretts Esophagus.