Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients

Elevated plasma lipopolysaccharide (LPS), an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD). To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL) assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP) levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV) co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes

Lipopolysaccharide-induced blood-brain barrier disruption: roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit

Background: Disruption of the blood-brain barrier (BBB) occurs in many diseases and is often mediated by inflammatory and neuroimmune mechanisms. Inflammation is well established as a cause of BBB disruption, but many mechanistic questions remain. Methods: We used lipopolysaccharide (LPS) to induce inflammation and BBB disruption in mice. BBB disruption was measured using 14C-sucrose and radioactively labeled albumin. Brain cytokine responses were measured using multiplex technology and dependence on cyclooxygenase (COX) and oxidative stress determined by treatments with indomethacin and N-acetylcysteine. Astrocyte and microglia/macrophage responses were measured using brain immunohistochemistry. In vitro studies used Transwell cultures of primary brain endothelial cells co- or tri-cultured with astrocytes and pericytes to measure effects of LPS on transendothelial electrical resistance (TEER), cellular distribution of tight junction proteins, and permeability to 14C-sucrose and radioactive albumin. Results: In comparison to LPS-induced weight loss, the BBB was relatively resistant to LPS-induced disruption. Disruption occurred only with the highest dose of LPS and was most evident in the frontal cortex, thalamus, pons-medulla, and cerebellum with no disruption in the hypothalamus. The in vitro and in vivo patterns of LPS-induced disruption as measured with 14C-sucrose, radioactive albumin, and TEER suggested involvement of both paracellular and transcytotic pathways. Disruption as measured with albumin and 14C-sucrose, but not TEER, was blocked by indomethacin. N-acetylcysteine did not affect disruption. In vivo, the measures of neuroinflammation induced by LPS were mainly not reversed by indomethacin. In vitro, the effects on LPS and indomethacin were not altered when brain endothelial cells (BECs) were cultured with astrocytes or pericytes. Conclusions: The BBB is relatively resistant to LPS-induced disruption with some brain regions more vulnerable than others. LPS-induced disruption appears is to be dependent on COX but not on oxidative stress. Based on in vivo and in vitro measures of neuroinflammation, it appears that astrocytes, microglia/macrophages, and pericytes play little role in the LPS-mediated disruption of the BBB

A study of preferred and natural memory colours across different ethnic groups

A psychophysical experiment was carried out to specify the preferred and natural memory colours corresponding to 24 familiar objects on mobile displays. These objects were selected to cover a large colour gamut in CIELAB space. One hundred and six observers from five different ethnic groups participated. Forty-nine colours for each object were rendered three-dimensionally to cover a large colour range. The results showed inter-observer variations are small between different ethnic groups, about 1.4 and 1.3 CIEDE2000 colour difference units for naturalness and preference, respectively. Comparing the preference and the naturalness colour centres, the preferred colours are brighter and more colourful than naturalness colours, by 1 and 2 units in L* and C*ab attributes, respectively. Both sets of data show a great hue consistency. The results showed that different ethnic groups agreed well on the objects studied. It was found that the best-agreed objects are strawberry, green apple, tomato, corn and purple grape, and the worst-agreed objects are blueberry, broccoli, smurf, green pepper and blue sky

Synthesis and Characterization of Organic/Inorganic Hybrid Star Polymers of 2,2,3,4,4,4-Hexafluorobutyl Methacrylate and Octa(aminophenyl)silsesquioxane Nano-Cage Made via Atom Transfer Radical Polymerization

Well-defined organic/inorganic hybrid fluorinated star polymers were synthesized via atom transfer radical polymerization (ATRP) of 2,2,3,4,4,4-hexafluorobutyl methacrylate (HFBMA) using octa(aminophenyl)silsesquioxane (OAPS) nano-cage as initiator. For this purpose, OAPS was transformed into ATRP initiator by reacting with 2-bromoisobutyrylbromide. ATR polymerization of HFBMA was carried out in trifluorotoluene at 75 degrees C using CuCl/2,2-bipyridine or N,N,N',N",N"-pentamethyldi-ethylenetriamine as catalyst system. GPC and H-1 NMR data confirmed the synthesis of OAPS/PHFBMA hybrid star polymer. Kinetics of the ATR polymerization of HFBMA using OAPS nano-cage initiator was also investigated. The OAPS/PHFBMA hybrid stars were found to be molecularly dispersed in solution (THF); however, TEM micrographs revealed the formation of spherical particles of similar to 120-180 nm by the OAPS/PHFBMA hybrid star polymer after solvent evaporation. Thermal characterization of the nanocomposites by differential scanning calorimetry (DSC) revealed a slightly higher glass transition temperature (T-g) (when compared with the linear PRFBMA) of higher molecular weight OAPS/PHFBMA hybrid star polymers. In contrast, lower T-g than the linear PHFBMA was observed for OAPS/PHFBMA of relatively lower molecular weight (but higher than the linear PHFBMA). Thermal gravimetric analysis (TGA) showed a significant retardation (by similar to 60 degrees C) in thermal decomposition of nanocomposites when compared with the linear PHFBMA. Additionally, surface properties were evaluated by measuring the contact angles of water on polymer surfaces. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym, Chem 46: 7287-7298, 200

Metal ion Exchange in Dinuclear Macrocyclic Complexes Identified by Electrospray Mass Spectrometry

Dicopper(I) complexes of a two-compartment 34-membered bis-dithiadiimine macrocycle (1) in solution in the presence of silver(I) ion display in electrospray mass spectrometry experiments the presence of AgCu(1)(2+) and Ag-2(1)(2+) in addition to the original Cu-2(1)(2+), consistent with metal ion exchange in this helical complex occurring without fragmentation. (C) 1999 Elsevier Science S.A. All rights reserved.</p