Biodistribution of gold nanoparticles in mouse lung following intratracheal instillation

<p>Abstract</p> <p>Background</p> <p>The fate of gold nanoparticles, 2, 40 and 100 nm, administered intratracheally to adult female mice was examined. The nanoparticles were traced by autometallography (AMG) at both ultrastructural and light microscopic levels. Also, the gold content was quantified by inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA). The liver is the major site of deposition of circulating gold nanoparticles. Therefore the degree of translocation was determined by the hepatic deposition of gold. Mice were instilled with 5 intratracheal doses of gold nanoparticles distributed over a period of 3 weeks and were killed 24 h after the last dose. One group of mice were given a single intratracheal dose and were killed after 1 h.</p> <p>Results</p> <p>The instilled nanoparticles were found in lung macrophages already 1 h after a single instillation. In mice instilled treated repeatedly during 3 weeks, the load was substantial. Ultrastructurally, AMG silver enhanced gold nanoparticles were found in lysosome-/endosome-like organelles of the macrophages and analysis with AMG, ICP-MS and NAA of the liver revealed an almost total lack of translocation of nanoparticles. In mice given repeated instillations of 2 nm gold nanoparticles, 1.4‰ (by ICP-MS) to 1.9‰ (by NAA) of the instilled gold was detected in the liver. With the 40 nm gold, no gold was detected in the liver (detection level 2 ng, 0.1‰) except for one mouse in which 3‰ of the instilled gold was found in the liver. No gold was detected in any liver of mice instilled with 100 nm gold (detection level 2 ng, 0.1‰) except in a single animal with 0.39‰ of the dose in the liver.</p> <p>Conclusion</p> <p>We found that that: (1) inert gold nanoparticles, administered intratracheally are phagocytosed by lung macrophages; (2) only a tiny fraction of the gold particles is translocated into systemic circulation. (3) The translocation rate was greatest with the 2 nm gold particles.</p

Recent sexual violence exposure is associated with immune biomarkers of HIV susceptibility in women

Problem: HIV/AIDS and sexual violence act synergistically and compromise women\u27s health. Yet, immuno-biological mechanisms linking sexual violence and increased HIV susceptibility are poorly understood. Methods: We conducted a cross-sectional pilot study of HIV-uninfected women, comparing 13 women exposed to forced vaginal penetration within the past 12 weeks (Exposed) with 25 Non-Exposed women. ELISA assays were conducted for 49 biomarkers associated with HIV pathogenesis in plasma and cervicovaginal lavage (CVL). Differences between Exposed and Non-Exposed were analyzed by linear and logistic regression, using propensity score weighting to control for age, race, socioeconomic status, menstrual cycle, and contraceptive use. Results: In CVL, Exposed women had significantly reduced chemokines MIP-3α (p \u3c.01), MCP-1 (p \u3c.01), and anti-HIV/wound-healing thrombospondin-1 (p =.03). They also had significantly increased inflammatory cytokine IL-1α (p \u3c 0.01) and were more likely to have detectable wound-healing PDGF (p =.02). In plasma, Exposed women had reduced chemokines MIP-3α (p \u3c.01) and IL-8 (p \u3c.01), anti-inflammatory cytokine TGF-β (p =.02), anti-HIV/antimicrobial HBD–2 (p =.02), and wound-healing MMP-1 (p = 0.02). They also had increased thrombospondin-1 (p \u3c.01) and Cathepsin B (p =.01). After applying the stringent method of false discovery rate adjustment, differences for IL-1α (p =.05) and MCP-1 (p =.03) in CVL and MIP-3α (p =.03) in plasma remained significant. Conclusions: We report systemic and mucosal immune dysregulation in women exposed to sexual violence. As these biomarkers have been associated with HIV pathogenesis, dysregulation may increase HIV susceptibility