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51.
Natalie J. Kingston Liriye Kurtovic Renae Walsh Carina Joe George Lovrecz Stephen Locarnini James G. Beeson Hans J. Netter 《Vaccine》2019,37(12):1674-1684
The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the “Asp-Ala-Asp-Pro” (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy. 相似文献
52.
《Vaccine》2019,37(24):3190-3198
The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined. 相似文献
53.
Yuan Zhang Ying Zheng Xuesong Yang Xuqing Liu Haiying Zhang Xiaoluan Xu Fankun Meng 《Ultrasound in medicine & biology》2019,45(3):684-692
The purpose of this study was to compare acoustic structure quantification (ASQ) with transient elastography for staging liver fibrosis. One hundred eighty-two patients with chronic hepatitis B and without moderate to severe hepatic steatosis scheduled for liver biopsy underwent ASQ and transient elastography examinations. All ASQ parameters, including total mode, total average, red mode, red average, red standard deviation, blue mode, blue average, blue standard deviation and focal disturbance (FD) ratio and liver stiffness obtained via transient elastography were found to correlate with fibrosis stage (Spearman's r?=?0.783, 0.791, 0.750, 0.771, 0.544, 0.718, 0.691, 0.439, 0.815 and 0.814, respectively; all p values < 0.001). Among the ASQ parameters, the FD ratio had the highest correlation with the stage of fibrosis. The areas under the receiver operating characteristic curves (AUCs) of FD ratio and liver stiffness were 0.911 and 0.906 for F ≥ F1, 0.918 and 0.882 for F ≥ F2, 0.911 and 0.914 for F ≥ F3 and 0.926 and 0.978 for F?=?F4, respectively. There was no significant difference in AUCs between FD ratio and liver stiffness in predicting different stages of fibrosis (p?=?0.062–0.912). ASQ is a promising technique for assessing liver fibrosis in the absence of moderate to severe hepatic steatosis. 相似文献
54.
Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of nteeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth nteeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔEWSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔEWSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL. 相似文献
55.
BackgroundAutoimmune hepatitis is a chronic inflammatory disease, the abnormal immunological function is the main pathogenesis. Interleukin-34 is a newly identified cytokine that shares the same receptor as colony stimulating factor-1.MethodsWe used interleukin-34 knockout and wild-type mice in a Con A-induced hepatitis model and cocultured RAW264.7 macrophage cells with interleukin-34. We then detected associated inflammatory cytokine and chemokine levels to elucidate the role of interleukin-34.ResultsIn this study, we found that the loss of interleukin-34 resulted in higher sensitivity to Con A-induced hepatitis. RAW264.7 macrophage cells were able to differentiate to the M2 phenotype upon interleukin-34 stimulation.ConclusionsWe conclude that interleukin-34 may protect the liver from Con A-mediated hepatitis by driving M2 macrophage polarization and suppressing inflammation. 相似文献
56.
D.V. Pérez Civantos A. Muñoz Cantero M. Robles Marcos F. Fuentes Morillas M.O. Cerezo Arias H. Fariñas Seijas 《Transplantation proceedings》2019,51(2):353-358
Introduction
Adequate perfusion and oxygenation to liver graft after transplantation is essential for its viability. Hepatic oximetry (hepatic tissue oxygenation [LSrO2]) through near infrared spectroscopy (NIRS) can help by showing real time oxygen content of the graft.Methods
In this prospective study, we enrolled 50 consecutive patients undergoing liver transplant surgery from deceased donors.Liver NIRS (LSrO2) was continuously measured for 24 hours then analyzed and correlated with other clinical data such as hemoglobin (Hb), mixed venous oxygen saturation, cardiac index (CI), central venous pressure, arterial gases, diuresis, blood lactate, liver biochemistry, and normalized index ratio (INR). Severity disease scales and cold-warm ischemia time were also measured, as well as Doppler ultrasound (DUS) at hour 24. A statistical analysis with IBM SPSS 22 using Pearson correlation was carried out.Results
LSrO2 could anticipate serious bleeding and hemodynamic events showing a decrease >10% from basal data.We found a significant correlation between LSrO2 with CI at 3 hours (P=.044), hemoglobin (Hb) at hour 3 and 24 (P = .004 and P = .002, respectively), and with Apache II (P=.041).A significant correlation was also detected between cold ischemia and INR at hour 24 (P=.016).No correlation of LSrO2 was found with lactate, liver biochemistry, and DUS data. 相似文献57.
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60.
Rapid and sensitive HPLC-MS/MS method for quantitative determination of isochlorogenic acid B in rat plasma and its application in pharmacokinetic study 下载免费PDF全文
Asensitive LC-ESI-MS/MS method for determination of isochlorogenic acid B in rat plasma was developed and validated in the present study. Plasma samples were prepared by a simple protein precipitation with methanol containing resveratrol as internal standard (IS). The chromatographic separation was performed on a Zorbax SB-C18 column (3.5 μm, 2.1 mm×100 mm, Agilent, USA) at a flow rate of 0.2 mL/min using methanol/water containing 0.1% formic acid (v/v) as mobile phase. The detectionwas performed on a triple quadrupole tandem mass spectrometer equipped with Electronic Spray Ion by selected reaction monitoring (SRM) of the transitions at m/z 515.3→352.9 for isochlorogenic acid B and m/z 227.1→143.1 for IS, respectively. The calibration curve of the method was linear over the range of 5–2500 ng/mL (r2 = 0.9982). The intra- and inter-day precisions (R.S.D.%) were less than 12.46%, and the accuracy (R.E.%) was within ±5.80%. Isochlorogenic acid B was sufficiently stable under all relevant analytical conditions. The validated method was successfully applied to the plasma pharmacokinetic studies of isochlorogenic acid B in rats. It was found that isochlorogenic acid B had non-linear pharmacokinetic characteristics in rats within the dosage ranges from 5 to 20 mg/kg. 相似文献