Effectiveness of a silicone device for foot MRI in order to obtain homogeneous fat suppression images.

BACKGROUND: Incomplete fat suppression induced by magnetic field inhomogeneity is difficult to compensate for with hardware magnetic-field shimming. PURPOSE: To evaluate the effectiveness of a silicone device used to obtain homogeneous fat suppression during 3T magnetic resonance imaging (MRI) scans of the foot. MATERIAL AND METHODS: Thirty-eight healthy volunteers were enrolled and examined twice, before (group A) and after (group B) the application of a silicone device. Fat-saturated, T2-weighted, fast spin-echo images were acquired using the same scanning protocol at both examinations. Signal- and contrast-to-noise ratios (SNR and CNR) were calculated and compared in the four regions of interest (ROIs). ROI 1 and 2 were selected from toe-side bone and soft tissue, while ROI 3 and 4 were selected from proximal bone and soft tissue. Qualitative analysis using a four-point scale was performed for three categories. The categories are as follows: the overall image quality, homogeneity of the first phalange and metatarsal bone, respectively. RESULTS: The SNR and CNR in ROI 1 and 2 were significantly higher in group A than in group B (SNR; P < 0.001, CNR; P < 0.001), and there were no significant difference in ROI 3 and 4. The qualitative score of the overall fat suppression in group B was significantly higher than that in group A (P < 0.001). Homogeneity of the first phalange in group B was also significantly higher than that in group A (P < 0.001). On the other hand, the homogeneity of the metatarsal bone was not significantly different in the two groups. CONCLUSION: The use of a silicone device provides homogeneous fat suppression in 3T MRI of the foot and can significantly improve image quality.

The modification of alpha-synuclein by dicarbonyl compounds inhibits its fibril-forming process.

Oxidative modification of alpha-synuclein (alphaSyn) was reported to have significant effects on its amyloidogenic properties. Dicarbonyl compounds are metabolites accumulated by various oxidative processes in the intracellular environment. In this study, two dicarbonyl compounds, methylglyoxal (MGO) and glyoxal (GO), were investigated for their effects on the structural and fibril-forming properties of alphaSyn. Both compounds were found to induce the oligomerization of alphaSyn. By adding substoichiometric amounts of alphaSyn modified by MGO or GO, the fibrillization of alphaSyn was substantially inhibited. The heterogeneously-modified alphaSyns were separated into three fractions: monomers, oligomers, and high molecular mass oligomers. When each modified alphaSyn species was used to seed fibril formation, protein fibrillization was significantly suppressed. Temperature scanning and interactions with liposomes revealed that both MGO- and GO-modified monomers were not as susceptible as the unmodified alphaSyn to conformational changes into partially folded intermediates and alpha-helixes. Our observations suggest that dicarbonyl modification of alphaSyn reduces conformational flexibility of the protein, thereby contributing to a reduction in the ability of alphaSyn to form fibrils, and the modified protein inhibits the fibrillization of the unmodified alphaSyn.

Enhanced adhesion of osteoblastic cells on polystyrene films by independent control of surface topography and wettability.

We independently controlled surface topography and wettability of polystyrene (PS) films by CF4 and oxygen plasma treatments, respectively, to evaluate the adhesion and proliferation of human fetal osteoblastic (hFOB) cells on the films. Among the CF4 plasma-treated PS films with the average surface roughness ranging from 0.9 to 70 nm, the highest adhesion of hFOB cells was observed on a PS film with roughness of ~11 nm. When this film was additionally treated by oxygen plasma to provide a hydrophilic surface with a contact angle less than 10°, the proliferation of bone-forming cell was further enhanced. Thus, the plasma-based independent modification of PS film into an optimum nanotexture for human osteoblast cells could be appplied to materials used in bone tissue engineering.

Controlled release of human growth hormone fused with a human hybrid Fc fragment through a nanoporous polymer membrane.

Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.

Nuclear factor kappa B (NF-κB): a novel cause for diabetes, coronary artery disease and cancer initiation and promotion?

Obesity is a growing epidemic in the United States (US). Obesity has been recognized as a modifiable risk factor for many diverse diseases including diabetes, cardiovascular disease and cancer burden. Common contributors to obesity include a high fat diet, smoking and physical inactivity. Systemic effects of obesity include increased micro-inflammatory molecules such as nuclear factor kappa B (NF-κB) that influence the both endothelial and epithelial layers as well as the supportive stroma. An emerging risk factor for micro-inflammation also includes periodontal disease. These pro-inflammatory states are hypothesized to contribute to diabetes as well as cardiovascular disease and cancer through the direct activation of NF-κB. Therefore, a comprehensive health care strategy would include reduction of diabetes, cardiovascular and cancer risk through the decrease in micro-inflammation.

Effects of lateral spacing on enzymatic on-chip DNA polymerization.

Enzymatic on-chip DNA polymerization can be utilized to elongate surface-bound primers with DNA polymerase and to enhance the signal in the detection of target DNAs on the solid support. In order to investigate the steric effect of the enzymatic reaction on the solid support, we compared the efficiency of on-chip DNA polymerization on a high-density surface with that on a spacing-controlled surface. The spacing-controlled, 9-acid dendron-coated surface exhibited approximately 8-fold higher efficiency of on-chip DNA polymerization compared with the high-density surface. The increase in fluorescence intensity during the on-chip DNA polymerization could be fit to an exponential equation, and the saturation level of the 9-acid dendron slide was 7 times higher than that of the high-density slide. The on-chip DNA polymerization was employed to measure the transcription level of nine genes related to epithelial-to-mesenchymal transition in hepatocellular carcinoma cells. Compared to the high-density surface, the dendron-coated surface exhibited a lower detection limit in the on-chip DNA polymerization and higher correlation with transcription levels as determined by quantitative real-time PCR. Our results suggest that control of the lateral spacing of DNA strands on the solid support should significantly enhance the accessibility of DNA polymerase and the efficiency of the on-chip DNA polymerization.

Single-file diffusion of protein drugs through cylindrical nanochannels.

A new drug delivery device using cylindrical block copolymer nanochannels was successfully developed for controlled protein drug delivery applications. Depending on the hydrodynamic diameter of the protein drugs, the pore size in cylindrical nanochannels could be controlled precisely down to 6 nm by Au deposition. Zero-order release of bovine serum albumin (BSA) and human growth hormone (hGH) by single-file diffusion, which has been observed for gas diffusion through zeolite pores, was realized up to 2 months without protein denaturation. Furthermore, a nearly constant in vivo release of hGH from the drug delivery nanodevice implanted to Sprague-Dawley (SD) rats was continued up to 3 weeks, demonstrating the feasibility for long-term controlled delivery of therapeutic protein drugs.

Association of human tumor necrosis factor-related apoptosis inducing ligand with membrane upon acidification.

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) has been known to induce tumor-specific apoptosis and to share the structural and functional characteristics with the proteins of TNF family. Recently, the crystal structure of human TRAIL showed that TRAIL is a homotrimeric protein whose subunits contain mainly beta-sheets. We characterized the structural changes of recombinant human TRAIL induced by acidification and the biological implication of the structural characteristics at acidic pH in the interaction with the lipid bilayer. At acidic pH below pH 4.5, TRAIL resulted in substantial structural changes to a molten globule (MG)-like state. Far-UV CD spectrum of TRAIL indicated that the acidification induced alpha-helices that are absent in the native state. TRAIL at acidic pH exhibited significant change of tertiary structures as reflected in the near-UV CD spectrum. Thermal transition curve indicated that there was less cooperation at acidic pH than at neutral pH in the thermal denaturation of TRAIL. Moreover, TRAIL at the MG-like state not only enhanced the binding ability to liposomes, but also increased the release rate of a fluorescent dye, calcein, encapsulated in liposomes. The binding assay with anilinonaphthalene-8-sulfonic acid revealed that the surface hydrophobicity of TRAIL was increased while tryptophan residues became more exposed to solvent as judged by blue shift of the maximum fluorescence wavelength. Taken together, our results demonstrate that the acidification of human TRAIL induces the MG-like state in vitro and makes the membrane permeable through the favorable interaction of TRAIL with the membrane, implicating that general intrinsic properties such as TRAIL, TNF-alpha and lymphotoxin are shared by TNF family members.