Objective. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, is a carrier for drug delivery systems. This study was undertaken to investigate the tolerogenic effect of single administration of PLGA entrapping type II collagen (CII) on the development of collagen-induced arthritis (CIA).Methods. The biophysical properties of PLGA nanoparticles entrapping CII (PLGA-CII) were investigated by in vitro release testing of CII, immunohistochemistry analysis, and electron microscopy. PLGA-CII was fed singly to animals 14 days before immunization, and the effect on joint inflammation was assessed. Circulating IgG anti-CII antibodies and T cell responses to CII in draining lymph nodes were assayed by enzyme-linked immunosorbent assay and 3 H-thymidine incorporation assay, respectively. The expression of messenger RNA (mRNA) for transforming growth factor  (TGF) and tumor necrosis factor ␣ (TNF␣) was determined by reverse transcriptase-polymerase chain reaction.Results. The in vitro release test showed that CII was slowly discharged from PLGA-CII over a period of a month. After single administration of PLGA-CII, numerous particles ϳ300 nm in size were detectable in Peyer's patches, by electron microscopy and immunohistochemical staining for CII, 14 days after the original feeding. Mice fed a single dose of PLGA containing 40 g of CII had significantly reduced values for incidence and severity of arthritis, serum IgG anti-CII antibodies, and CII-specific T cell proliferation as compared with mice fed solvent alone, those fed 6 doses of 20 g CII alone, and those fed a single dose of PLGA alone. PLGA-CII was also able to suppress CIA after disease onset. Moreover, PLGA-CII-fed mice showed a higher level of TGF mRNA expression in Peyer's patches, but a lower level of TNF␣ mRNA expression in draining lymph nodes, compared with the other groups of mice.Conclusion. Our data show that PLGA may serve as a powerful vehicle to promote the tolerance effect of oral CII and that single administration of PLGA-CII may hold promise as a new treatment strategy in rheumatoid arthritis.
Plasma bubbles in the equatorial F region are thought of as nighttime phenomena because they develop at night and are assumed to vanish after sunrise. However, bubbles occasionally persist throughout the night and into the day. This study investigates the origin of daytime irregularities and their evolution using data from the first Republic of China satellite. Our results show that daytime irregularities occur in the longitudes where bubbles have developed on previous nights. A newly reported feature is the observation of the temporal variation of the locations of daytime irregularities; daytime irregularities are concentrated near the magnetic equator early in the morning, but the location gradually shifts to higher latitudes with time. This phenomenon is explained in terms of the latitudinal redistribution of fossil bubbles by the ionospheric fountain effect.
Electron density irregularities on the dayside in the low-latitude F region are understood as remnants (or fossils) of nighttime plasma bubbles. We provide observational evidence of the connection of daytime irregularities to nighttime bubbles and the transport of the daytime irregularities by the vertical motion of the background ionosphere. The distributions of irregularities are derived using the measurements of the ion density by the first Republic of China satellite from March 1999 to June 2004. The seasonal and longitudinal distributions of daytime and nighttime irregularities in low latitudes show a close similarity. The high occurrence rate of daytime irregularities at the longitudes where strong irregularities occur frequently at night provides strong evidence of the association of daytime irregularities with nighttime bubbles. Nighttime irregularities are concentrated in the equatorial region, whereas daytime irregularities spread over broader latitudes. The seasonal and longitudinal variation of the latitudinal spread of daytime irregularities is consistent with the morphologies of plasma density and vertical plasma velocity. The zonal wave number 4 pattern, which corresponds to that in plasma density, is identified in the distribution of daytime irregularities. These observations lead to the conclusion that the morphology of daytime irregularities in the low-latitude F region is dominated by the morphology of bubbles at night and the ionospheric fountain process on the dayside.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.