Concentrations of Pro-Inflammatory Cytokines Are Not Associated with Senescence Marker p16INK4a or Predictive of Intracellular Emtricitabine/Tenofovir Metabolite and Endogenous Nucleotide Exposures in Adults with HIV Infection

As the HIV-infected population ages, the role of cellular senescence and inflammation on co-morbid conditions and pharmacotherapy is increasingly of interest. p16INK4a expression, a marker for aging and senescence in T-cells, is associated with lower intracellular concentrations of endogenous nucleotides (EN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs). This study expands on these findings by determining whether inflammation is contributing to the association of p16INK4a expression with intracellular metabolite (IM) exposure and endogenous nucleotide concentrations

A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine

Background. A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic (PK) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP)

Complex flow in the nasal region of guitarfishes

Scent detection in an aquatic environment is dependent on the movement of water. We set out to determine the mechanisms for moving water through the olfactory organ of guitarfishes (Rhinobatidae, Chondrichthyes) with open nasal cavities. We found at least two. In the first mechanism, which we identified by observing dye movement in the nasal region of a life-sized physical model of the head of Rhinobatos lentiginosus mounted in a flume, olfactory flow is generated by the guitarfish's motion relative to water, e.g. when it swims. We suggest that the pressure difference responsible for motion-driven olfactory flow is caused by the guitarfish's nasal flaps, which create a region of high pressure at the incurrent nostril, and a region of low pressure in and behind the nasal cavity. Vortical structures in the nasal region associated with motion-driven flow may encourage passage of water through the nasal cavity and its sensory channels, and may also reduce the cost of swimming. The arrangement of vortical structures is reminiscent of aircraft wing vortices. In the second mechanism, which we identified by observing dye movement in the nasal regions of living specimens of Glaucostegus typus, the guitarfish's respiratory pump draws flow through the olfactory organ in a rhythmic (0.5-2 Hz), but continuous, fashion. Consequently, the respiratory pump will maintain olfactory flow whether the guitarfish is swimming or at rest. Based on our results, we propose a model for olfactory flow in guitarfishes with open nasal cavities, and suggest other neoselachians which this model might apply to

Models for Predicting Effective HIV Chemoprevention in Women

Model systems which rapidly identify tissue drug concentrations protective of HIV infection could streamline the development of chemoprevention strategies. Tissue models are promising, but limited concentration targets exist, and no systematic comparison to cell models or clinical studies has been performed