Cross-neutralization between vaccine and circulating wild-type mumps viruses in Korea

Mumps is a contagious disease caused by the mumps virus. It can be prevented using mumps vaccines, administered as a measles-mumps-rubella (MMR) vaccine. For first and second dose immunization, children aged 12–15 months and 4–6 years have been administered this vaccine since 1997 in Korea. Nevertheless, mumps outbreaks still occur in vaccinated populations worldwide. Hence, immunity against these diseases may be attenuated, or there are antigenic differences between currently available vaccine strains and circulating wild-type viruses. After the introduction of national immunization programs in Korea, mumps cases became sporadic. Viral genotypes F, H, and I have emerged since 1998 whereas the vaccine strains belong to genotype A. Here, we compared the amino acid sequences of the haemagglutinin-neuraminidase (HN) gene from wild-type viruses and the mumps vaccine and measured the cross-neutralization titers between them. We selected the F, H, and I wild-type mumps strains circulating in Korea from 1998 to 2016 and analyzed changes in the amino acid sequence of the protein encoded by the HN gene. We measured mumps virus-specific IgG and rapid focus reduction neutralization test (FRNT) titers in Korean isolates and sera obtained from 50 children aged 1–2 years who had been administered a single dose of MMR vaccine. Analysis of the HN protein sequences disclosed no changes in the glycosylation sites but did reveal 4–5 differences between the Korean isolates and the genotype A vaccine strain in terms of the neutralizing epitope sites on their HN proteins. Post-vaccination FRNT titers were significantly lower against genotypes F, H, and I than they were against genotype A. This finding highlights the possibility of a recurrence of mumps outbreaks in vaccinated populations depending on the degree of genetic conservation of the HN gene. Further research into this issue is needed to prevent the resurgence of mumps.     

Quantitative Estimation of Plasma Free Drug Fraction in Patients With Varying Degrees of Hepatic Impairment: A Methodological Evaluation

Quantitative prediction of unbound drug fraction (f_u) is essential for scaling pharmacokinetics through physiologically based approaches. However, few attempts have been made to evaluate the projection of f_u values under pathological conditions. The primary objective of this study was to predict f_u values (n = 105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein associated with differing levels of hepatic dysfunction. For the purpose of scaling, data pertaining to albumin and α1-acid glycoprotein levels in response to differing degrees of hepatic impairment were systematically collected from 919 adult donors. The results of the present study demonstrate for the first time the feasibility of physiologically based scaling f_u in hepatic dysfunction after verifying with experimentally measured data of a wide variety of compounds from individuals with varying degrees of hepatic insufficiency. Furthermore, the high level of predictive accuracy indicates that the inter-relation between the severity of hepatic impairment and these plasma protein levels are physiologically accurate. The present study enhances the confidence in predicting f_u in hepatic insufficiency, particularly for albumin-bound drugs.     

Anti-Inflammatory Activity in the Low Molecular Weight Fraction of Commercial Human Serum Albumin (LMWF5A)

The innate immune system is increasingly being recognized as a critical component in osteoarthritis (OA) pathophysiology. An ex vivo immunoassay utilizing human peripheral blood mononuclear cells (PBMC) was developed in order to assess the OA anti-inflammatory properties of the low molecular weight fraction (<5 kDa) of commercial human serum albumin (LMWF5A). PBMC from various donors were pre-incubated with LMWF5A before LPS stimulation. TNFα release was measured by ELISA in supernatants after an overnight incubation. A ≥ 30% decrease in TNFα release was observed. This anti-inflammatory effect is potentially useful in assessing potency of LMWF5A for the treatment of OA.     

2型糖尿病肾病患者脂蛋白(a)的临床应用价值探讨

目的 探讨24 h-UAER、Lp(a)对2型糖尿病肾病早期诊断的临床应用价值.方法 选取糖尿病患者329例,根据尿蛋白实验阳性程度分为4组,采用免疫透射比浊法分别定量检测24 h-UAER、Lp(a),对两定量指标进行相关分析,并与健康对照组比较.结果 方差分析显示,各组24 h-UAER、Lp(a)水平均不同(P＜0.01),糖尿病患者各组均高于健康对照组.经q检验显示,尿蛋白阴性组与健康对照组比较,Lp(a)水平差异无统计学意义(P＞0.05),24 h-UAER水平差异有统计学意义(P＜0.01);尿蛋白阳性病例Lp(a)与24 h-UAER呈正相关,相关性较好;Lp(a)水平高于正常参考值上限的检出率,尿蛋白阴性组和尿蛋白±～+组分别为11.4%和18.7%,与健康对照组比较差异无统计学意义(P＞0.05);尿蛋白++组、尿蛋白+++以上组分别为55.0%和80.2%,与健康对照组比较差异有统计学意义(P＜0.05,P＜0.01).结论 Lp(a)可作为2型糖尿病早期肾损害的实验性指标,对糖尿病肾病早期诊断和防治具有现实的指导意义和临床应用价值.     

经皮冠状动脉PCI治疗术缺血修饰蛋白标志物的变化及意义

目的 研究经皮冠状动脉PCI治疗术后缺血修饰蛋白标志物的变化及意义.方法 选择接受急诊经皮冠状动脉支架术治疗的急性心肌梗死患者,按治疗后30 minMA水平分为MA升高组和MA正常组,检测治疗前后外周血TnT、CK-MB水平.结果 治疗后30 min,MA水平(0.37±0.06) ABSU、较治疗前明显升高(P＜0.05),cTnT、CK-MB水平无明显变化；治疗后6h和24 h cTnT、CK-MB水平明显升高,并且MA升高组上述心肌损伤指标明显升高,而MA正常组无明显改变.结论 缺血修饰白蛋白水平在PCI治疗后30 min内就会发生改变,是预测PCI治疗后心肌损伤的敏感指标.     

Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (P_app) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10^?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.     

Human Antibody Fragments Specific for the Epidermal Growth Factor Receptor Selected from Large Non-immunised Phage Display Libraries

Antibodies to EGFR have been shown to display anti-tumour effects mediated in part by inhibition of cellular proliferation and angiogenesis, and by enhancement of apoptosis. Humanised antibodies are preferred for clinical use to reduce complications with HAMA and HAHA responses frequently seen with murine and chimaeric antibodies. We have used depletion and subtractive selection strategies on cells expressing the EGFR to sample two large antibody fragment phage display libraries for the presence of human antibodies which are specific for the EGFR. Four Fab fragments and six scFv fragments were identified, with affinities of up to 2.2 nM as determined by BIAcore analysis using global fitting of the binding curves to obtain the individual rate constants (k_a and k_d). This overall approach offers a generic screening method for the identification of growth factor specific antibodies and antibody fragments from large expression libraries and has potential for the rapid development of new therapeutic and diagnostic reagents.     

Use of Cortisone and Antibiotics in Resistant Pelvic Infections

Although the incidence of resistant pelvic infections has been decreased, they are still a problem in spite of adequate antibiotic therapy. A new approach to such cases, in the subacute stage, is described, and the method, rationale and dangers outlined. Results obtained in the cases described, as well as in others treated subsequently, have been excellent.