Infusion of HIV-1 Nef-expressing astrocytes into the rat hippocampus induces enteropathy and interstitial pneumonitis and increases blood-brain-barrier permeability.

Even though HIV-1 replication can be suppressed by combination antiretroviral therapy (cART) inflammatory processes still occur, contributing to comorbidities. Comorbidities are attributed to variety of factors, including HIV-1 mediated inflammation. Several HIV-1 proteins mediate central nervous system (CNS) inflammation, including Nef. Nef is an early HIV-1 protein, toxic to neurons and glia and is sufficient to cause learning impairment similar to some deficits observed in HIV-1 associated neurocognitive disorders. To determine whether hippocampal Nef expression by astrocytes contributes to comorbidities, specifically peripheral inflammation, we infused Sprague Dawley rats with GFP- (control) or Nef-transfected astrocytes into the right hippocampus. Brain, lung, and ileum were collected postmortem for the measurement of inflammatory markers. Increased blood-brain-barrier permeability and serum IL-1β levels were detected in the Nef-treated rats. The lungs of Nef-treated rats demonstrated leukocyte infiltration, macrophage upregulation, and enhanced vascular permeability. Ileal tissue showed reactive follicular lymphoid hyperplasia, increased permeability and macrophage infiltration. The intracerebroventricular application of IL-1 receptor antagonist reduced infiltration of immune cells into ileum and lung, indicating the important role of IL-1β in mediating the spread of inflammation from the brain to other tissues. This suggests that localized expression of a single viral protein, HIV-1 Nef, can contribute to a broader inflammatory response by upregulation of IL-1β. Further, these results suggest that Nef contributes to the chronic inflammation seen in HIV patients, even in those whose viremia is controlled by cART

The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops

The topic of this book is dedicated to the analysis, fate, metabolism, effects, and remediation of pharmaceutically active compounds in water-soil-biota systems. While the majority of readers are likely to already have a broad understanding of potential entry points, flows, transformation pathways, and temporary and permanent sinks of drugs in the environment, the objectives of this first chapter are fourfold: (a) to provide a concise overview of the journey a drug takes from its inception at the laboratory bench to the desk of the reviewer at the regulatory agency; (b) to understand the biological and physiological processes a drug undergoes from administration to humans – or to the animal in case of veterinary medicines – to their excretion and ultimately discharge into wastes; (c) to describe the physico-chemical space small-molecule drugs reside in as this characteristic largely governs their later environmental fate; (d) to review their presence, fate, and metabolism in crops and plants determined using innovative analytical methods; as well as (e) to evaluate the effects and remediation of drugs in crops and biota.Peer reviewe