Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells

One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood–brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment

Evaluation of annoyance from the wind turbine noise: A pilot study

Objectives: The overall aim of this study was to evaluate the perception of and annoyance due to the noise from wind turbines in populated areas of Poland. Material and Methods: The study group comprised 156 subjects. All subjects were asked to fill in a questionnaire developed to enable evaluation of their living conditions, including prevalence of annoyance due to the noise from wind turbines and the self-assessment of physical health and well-being. In addition, current mental health status of the respondents was assessed using Goldberg General Health Questionnaire GHQ-12. For areas where the respondents lived, A-weighted sound pressure levels (SPLs) were calculated as the sum of the contributions from the wind power plants in the specific area. Results: It has been shown that the wind turbine noise at the calculated A-weigh­ted SPL of 30-48 dB was noticed outdoors by 60.3% of the respondents. This noise was perceived as annoying outdoors by 33.3% of the respondents, while indoors by 20.5% of them. The odds ratio of being annoyed outdoors by the wind turbine noise increased along with increasing SPLs (OR = 2.1; 95% CI: 1.22-3.62). The subjects' attitude to wind turbines in general and sensitivity to landscape littering was found to have significant impact on the perceived annoyance. About 63% of variance in outdoors annoyance assessment might be explained by the noise level, general attitude to wind turbines and sensitivity to landscape littering. Conclusions: Before firm conclusions can be drawn further studies are needed, including a larger number of respondents with different living environments (i.e., dissimilar terrain, different urbanization and road traffic intensity)

18β-Glycyrrhetinic Acid Delivered Orally Induces Isolated Lymphoid Follicle Maturation at the Intestinal Mucosa and Attenuates Rotavirus Shedding

Glycyrrhizin, an abundant bioactive component of the medicinal licorice root is rapidly metabolized by gut commensal bacteria into 18β-glycyrrhetinic acid (GRA). Either or both of these compounds have been shown to have antiviral, anti-hepatotoxic, anti-ulcerative, anti-tumor, anti-allergenic and anti-inflammatory activity in vitro or in vivo. In this study, the ability of GRA to modulate immune responses at the small intestinal mucosa when delivered orally was investigated. Analysis of cytokine transcription in duodenal and ileal tissue in response to GRA treatment revealed a pattern of chemokine and chemokine receptor gene expression predictive of B cell recruitment to the gut. Consistent with this finding, GRA induced increases in CD19(+) B cells in the lamina propria and B220(+) B cell aggregates framed by CD11c(+) dendritic cells in structures resembling isolated lymphoid follicles (ILF). Using a mouse model of rotavirus infection, GRA reduced the duration of viral antigen shedding, and endpoint serum antibody titers were higher in GRA-treated animals. Together the data suggest GRA delivered orally augments lymphocyte recruitment to the intestinal mucosa and induces maturation of B cell-rich ILF independently of ectopic antigenic stimulus. These results provide further support a role for dietary ligands in modulation of dynamic intestinal lymphoid tissue