Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments: Potential applications

AbstractThis review describes the preparation of core-corona type polymeric nanoparticles and their applications in various technological and biomedical fields. Over the past two decades, we have studied the synthesis and clinical applications of core-corona polymeric nanoparticles composed of hydrophobic polystyrene and hydrophilic macromonomers. These nanoparticles were utilized as catalyst carriers, carriers for oral peptide delivery, virus capture agents, and vaccine carriers, and so on. Moreover, based on this research, we attempted to develop novel biodegradable nanoparticles composed of hydrophobic poly(γ-glutamic acid) (γ-PGA) derivatives (γ-hPGA). Various model proteins were efficiently entrapped on/into the nanoparticles under different conditions: encapsulation, covalent immobilization, and physical adsorption. The encapsulation method showed the most promising results for protein loading. It is expected that biodegradable γ-hPGA nanoparticles can encapsulate and immobilize various biomacromolecules. Nanoparticles consisting of hydrophobic and hydrophilic segments have great potential as multifunctional carriers for pharmaceutical and biomedical applications, such as drug, protein, peptide or DNA delivery systems

Uptake of biodegradable poly(γ-glutamic acid) nanoparticles and antigen presentation by dendritic cells in vivo

AbstractPoly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) carrying antigens have been shown to induce potent antigen-specific immune responses. However, in vivo delivery of γ-PGA NPs to dendritic cells (DCs), a key regulator of immune responses, still remains unclear. In this study, γ-PGA NPs were examined for their uptake by DCs and subsequent migration from the skin to the regional lymph nodes (LNs) in mice. After subcutaneous injection of fluorescein 5-isothiocyanate (FITC)-labeled NPs or FITC-ovalbumin (OVA)-carrying NPs (FITC-OVA-NPs), DCs migrated from the skin to the LNs and maturated, resulting in the upregulation of the costimulatory molecules CD80 and CD86 and the chemokine receptor CCR7. However, the migrated DCs were not detected in the spleen. FITC-OVA-NPs were found to be taken up by skin-derived CD103+ DCs, and the processed antigen peptides were cross-presented by the major histocompatibility complex (MHC) class I molecule of DCs. Furthermore, significant activation of antigen-specific CD8+ T cells was observed in mice immunized with OVA-carrying NPs (OVA-NPs) but not with OVA alone or OVA with an aluminum adjuvant. The antigen-specific CD8+ T cells were induced within 7 days after immunization with OVA-NPs. Thus, γ-PGA NPs carrying various antigens may have great potential as an antigen-delivery system and vaccine adjuvant in vivo

Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice

Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH

First Detection of NaI D lines in High-Redshift Damped Lyman-alpha Systems

A Near-infrared (1.18-1.35 micron) high-resolution spectrum of the gravitationally-lensed QSO APM 08279+5255 was obtained with the IRCS mounted on the Subaru Telescope using the AO system. We detected strong NaI D 5891,5897 doublet absorption in high-redshift DLAs at z=1.062 and 1.181, confirming the presence of NaI, which was first reported for the rest-frame UV NaI 3303.3,3303.9 doublet by Petitjean et al. This is the first detection of NaI D absorption in a high-redshift (z>1) DLA. In addition, we detected a new NaI component in the z=1.062 DLA and four new components in the z=1.181 DLA. Using an empirical relationship between NaI and HI column density, we found that all "components" have large HI column density, so that each component is classified as DLA absorption. We also detected strong NaI D absorption associated with a MgII system at z=1.173. Because no other metal absorption lines were detected in this system at the velocity of the NaI absorption in previously reported optical spectra (observed 3.6 years ago), we interpret this NaI absorption cloud probably appeared in the line of sight toward the QSO after the optical observation. This newly found cloud is likely to be a DLA based upon its large estimated HI column density. We found that the N(NaI)/N(CaII) ratios in these DLAs are systematically smaller than those observed in the Galaxy; they are more consistent with the ratios seen in the Large Magellanic Cloud. This is consistent with dust depletion generally being smaller in lower metallicity environments. However, all five clouds of the z=1.181 system have a high N(NaI)/N(CaII) ratio, which is characteristic of cold dense gas. We tentatively suggest that the host galaxy of this system may be the most significant contributor to the gravitational-lens toward APM 08279+5255.Comment: 22 pages, 6 Postscript figures, 3 tables, ApJ in press (Vol.643, 2 June 2006

Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure

Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure.BackgroundIn patients with chronic renal failure (CRF), abnormalities in vitamin D metabolism are known to be present, and several factors could contribute to the abnormalities.MethodsWe measured serum levels of three vitamin D metabolites, 1,25(OH)2D, 24,25(OH)2D and 25(OH)D, and analyzed factors affecting their levels in 76 nondialyzed patients with CRF (serum creatinine> 1.6 and < 9.0 mg/dl), 37 of whom had diabetes mellitus (DM-CRF) and 39 of whom were nondiabetic (nonDM-CRF).ResultsSerum levels of 1,25(OH)2D were positively correlated with estimated creatinine clearance (CCr; r = 0.429; P < 0.0001), and levels of 24,25(OH)2D were weakly correlated with CCr (r = 0.252, P < 0.05); no correlation was noted for 25(OH)D. Serum levels of all three vitamin D metabolites were significantly and positively correlated with serum albumin. Although there were no significant differences in age, sex, estimated CCr, calcium and phosphate between DM-CRF and nonDM-CRF, all three vitamin D metabolites were significantly lower in DM-CRF than in nonDM-CRF. To analyze factors influencing vitamin D metabolite levels, we performed multiple regression analyses. Serum 25(OH)D levels were significantly and independently associated with serum albumin, presence of DM and serum phosphate (R2 = 0.599; P < 0.0001). 24,25(OH)2D levels were significantly and strongly associated with 25(OH)D (β; = 0.772; R2 = 0.446; P < 0.0001). Serum 1,25(OH)2D levels were significantly associated only with estimated CCr (R2 = 0.409; P < 0.0001).ConclusionsThese results suggest that hypoalbuminemia and the presence of DM independently affect serum 25(OH)D levels, probably via diabetic nephropathy and poor nutritional status associated with diabetes, and that 25(OH)D is actively catalyzed to 24,25(OH)2D in CRF, probably largely via extrarenal 24-hydroxylase. Serum levels of 1,25(OH)2D were significantly affected by the degree of renal failure. Thus, this study indicates that patients with CRF, particularly those with DM, should receive supplements containing the active form of vitamin D prior to dialysis

H2_2 Emission Nebulosity Associated with KH 15D

An H$_2$ emission filament is found in close proximity to the unique object KH 15D using the adaptive optics system of the Subaru Telescope. The morphology of the filament, the presence of spectroscopic outflow signatures observed by Hamilton et al., and the detection of extended H$_2$ emission from KH 15D by Deming, Charbonneau, & Harrington suggest that this filament arises from shocked H$_2$ in an outflow. The filament extends about 15" to the north of KH 15D.Comment: 11 pages, 3 figures, 1 table. Astrophysical Journal Letters, in pres

Near-Infrared Adaptive Optics Spectroscopy of Binary Brown Dwarf HD 130948B and C

We present near-infrared spectroscopy of low-mass companions in a nearby triple system HD 130948 (Gliese 564, HR 5534). Adaptive optics on the Subaru Telescope allowed spectroscopy of the individual components of the 0".13 binary system. Based on a direct comparison with a series of template spectra, we determined the spectral types of HD 130948B and C to be L4 +- 1. If we take the young age of the primary star into account (0.3-0.8 Gyr), HD 130948B and C most likely are a binary brown dwarf system.Comment: 6 pages, 3 figures, accepted for publication in ApJ Letter