The rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo

Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes.     

A method to maintain the thickness of the mouthguard after the vacuum forming process: changes of the holding conditions of the mouthguard sheet

The aim of this study was to investigate differences in the thickness of the mouthguard sheet according to the holding conditions during heating. The material used in this study was Sports Mouthguard (3.8 mm thickness), and two holding conditions of the sheet were undertaken: one was the condition that the sheet was held all around the periphery and the other was that the sheet was held at only four points. The sheets were formed using a vacuum former when the sheets were heated until they hung 2.0 cm from the baseline. We measured the thickness of each part of the mouthguard and calculated the ratio of changes in the thickness. The difference in the thickness by the holding conditions at the area of the sheet that fitted over the anterior teeth, palate, and posterior teeth was analyzed by the paired t-test. The results showed that the thickness of the sheet differed statistically and significantly at the regions of the sheet that fitted over the anterior teeth and posterior teeth (P < 0.01) and the palate (P < 0.05) according to the holding conditions of the sheet. The thickness of the condition that the sheet was held all around the periphery was thinner than that of the condition that the sheet was held at only four points. These results suggested that the thickness of the sheet was maintained by holding the sheet only at four points, and this new method could be an effective way to maintain the thickness of the mouthguard in clinical use.     

Influence of color difference of mouthguard sheet on thickness after forming

PurposeThe aim of this study was to determine the color difference of mouthguard in hardness, water sorption and thickness after forming EVA sheets. Six different colors of sheets were tested for each of three manufacturers.MethodsThe materials used in this study were mouthguard sheets made by three manufacturers. Each manufacturer supplied six colors: clear, white, yellow, blue, red, and black. Shore A hardness and water sorption were measured based on ISO 7619 and 1817, respectively. The thickness after formation was measured by using a measuring device. The differences in hardness, water sorption and thickness after formation were analyzed by two-way analysis of variance. The correlation between the hardness and changes in thickness was analyzed using Pearson's product-moment correlation coefficient.ResultsShore A hardness was different depending upon various colored sheets and manufactures. There were differences in the water sorption depending upon some colored sheet among manufacturers. There was a significant difference in the thickness after formation was found to be dependent upon few colors of the sheets on one manufacturer's product on the anterior teeth and on three products on posterior teeth. A negative correlation between the hardness and the change of thickness was found in two products.ConclusionsThe present study suggests that the Shore A hardness and thickness after formation varied depending upon the colors of the EVA sheets and manufactures. A correlation between the hardness and change of thickness was observed in two manufactures that suggests that the hard sheets tend to reduce in thickness greater than that in softer ones.     

LecT-hepa, a glyco-marker derived from multiple lectins, as a predictor of liver fibrosis in chronic hepatitis C patients

Assessment of liver fibrosis in patients with chronic hepatitis C (CHC) is critical for predicting disease progression and determining future antiviral therapy. LecT-Hepa, a new glyco-marker derived from fibrosis-related glyco-alteration of serum alpha 1-acid glycoprotein, was used to differentiate cirrhosis from chronic hepatitis in a single-center study. Herein, we aimed to validate this new glyco-marker for estimating liver fibrosis in a multicenter study. Overall, 183 CHC patients were recruited from 5 liver centers. The parameters Aspergillus oryzae lectin (AOL) / Dature stramonium lectin (DSA) and Maackia amurensis lectin (MAL)/DSA were measured using a bedside clinical chemistry analyzer in order to calculate LecT-Hepa levels. The data were compared with those of seven other noninvasive biochemical markers and tests (hyaluronic acid, tissue inhibitor of metalloproteases-1, platelet count, aspartate aminotransferase-to-platelet ratio index [APRI], Forns index, Fib-4 index, and Zeng's score) for assessing liver fibrosis using the receiver-operating characteristic curve. LecT-Hepa correlated well with the fibrosis stage as determined by liver biopsy. The area under the curve (AUC), sensitivity, and specificity of LecT-Hepa were 0.802, 59.6%, and 89.9%, respectively, for significant fibrosis; 0.882, 83.3%, and 80.0%, respectively, for severe fibrosis; and 0.929, 84.6%, and 88.5%, respectively, for cirrhosis. AUC scores of LecT-Hepa at each fibrosis stage were greater than those of the seven aforementioned noninvasive tests and markers. Conclusion: The efficacy of LecT-Hepa, a glyco-marker developed using glycoproteomics, for estimating liver fibrosis was demonstrated in a multicenter study. LecT-Hepa given by a combination of the two glyco-parameters is a reliable method for determining the fibrosis stage and is a potential substitute for liver biopsy. (HEPATOLOGY 2012).     

Effect of sumatriptan on gastric emptying: a crossover study using the BreathID system

AIM:To determine the effect of oral sumatriptan on gastric emptying using a continuous 13 C breath test(BreathID system).METHODS:Ten healthy male volunteers participated in this randomized,2-way crossover study.The subjects fasted overnight and were randomly assigned to receive a test meal(200 kcal/200 mL) 30 min after pre-medication with sumatriptan 50 mg(sumatriptan condition),or the test meal alone(control condition).Gastric emptying was monitored for 4 h after administration of the test meal by the 13 C-acetic acid breath test performed continually using the BreathID system.Then,using Oridion Research Software(β version),the time taken for emptying of 50% of the labeled meal(T 1/2) similar to the scintigraphy lag time for 10% emptying of the labeled meal(T lag),the gastric emptying coefficient(GEC),and the regression-estimated constants(β and κ) were calculated.The statistical significance of any differences in the parameters were analyzed using Wilcoxon’s signed-rank test.RESULTS:In the sumatriptan condition,significant differences compared with the control condition were found in T 1/2 [median 131.84 min(range,103.13-168.70) vs 120.27 min(89.61-138.25);P = 0.0016],T lag [median 80.085 min(59.23-125.89) vs 61.11 min(39.86-87.05);P = 0.0125],and β [median 2.3374(1.6407-3.8209) vs 2.0847(1.4755-2.9269);P = 0.0284].There were no significant differences in the GEC or κ between the 2 conditions.CONCLUSION:This study showed that oral sumatriptan significantly delayed gastric emptying of a liquid meal.