HepG2 cells develop polarity over time, resulting in the formation and remodeling of bile canalicular (BC) structures. HepG2 cells expressing CD81 provide a model system to study the effects of hepatic polarity on HCV infection. We found an inverse association between HepG2-CD81 polarization and HCV pseudoparticle entry. As HepG2 cells polarize, discrete pools of claudin-1 (CLDN1) at the TJ and basal/lateral membranes develop, consistent

with the pattern of receptor staining observed in liver tissue. The TJ and nonjunctional pools of CLDN1 show an altered association with CD81 and localization in response to the PKA antagonist Rp-8-Br-cyclic AMPs (cAMPs). Rp-8-Br-cAMPs reduced CLDN1 expression at the basal membrane and inhibited HCV infection, supporting a model where the nonjunctional Citarinostat cell line pools of CLDN1 DMXAA mouse have a role in HCV entry. Treatment of HepG2 cells with proinflammatory cytokines, tumor necrosis factor alpha and gamma interferon,

perturbed TJ integrity but had minimal effect(s) on cellular polarity and HCV infection, suggesting that TJ integrity does not limit HCV entry into polarized HepG2 cells. In contrast, activation of PKC with phorbol ester reduced TJ integrity, ablated HepG2 polarity, and stimulated HCV entry. Overall, these data show that complex hepatocyte-like polarity alters CLDN1 localization and limits HCV entry, suggesting that agents which disrupt hepatocyte polarity may promote HCV infection and transmission within the liver.”
“Active compounds in cannabis such as tetrahydrocannabinol

(THC) interact with the inhibitory neurotransmitter delta-aminobutyric acid (GABA) but little is known about the functional effects of cannabis on human cortical brain processes. Therefore, the aim of the study was to investigate whether patients with chronic cannabis use Quisqualic acid demonstrate abnormalities in cortical inhibition or excitability. In all, 42 chronic cannabis using subjects (divided into heavy and light using subjects) and 19 controls were included in the study. Single and paired pulse transcranial magnetic stimulation were used to assess a number of parameters of cortical inhibition and cortical excitability. In addition, psychomotor function and THC plasma levels were measured. Both cannabis using groups (heavy and light use) demonstrated a reduction in short interval cortical inhibition compared with healthy controls, but there was no difference in other measures of cortical inhibition or cortical excitability. There was also no difference between the two groups on measures of psychomotor performance. Chronic cannabis use is associated with a reduction in cortical inhibition potentially related to activity at the GABA(A) receptors.