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.     

Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [¹²⁵I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.     

鼻内镜术后不同冲洗液冲洗鼻腔的效果对比

目的:观察鼻渊通窍颗粒稀释液与生理盐水对鼻内镜术后鼻腔冲洗的效果。方法:临床纳入进行功能性内窥镜鼻窦手术患者90例,研究组给予鼻渊通窍颗粒稀释液,对照组给予生理盐水。每周定期对患者进行鼻内窥镜的检查,观察两组患者4周内鼻腔症状以及术腔清洁、囊泡形成、肉芽生成等体征变化情况。结果:两组术后4周冲洗治疗结果表明,两者均有治疗作用,且治疗效果相当,但鼻渊通窍颗粒稀释液冲洗在术后第2周时对术腔痂皮脱落、黏膜水肿、鼻分泌物减少、囊泡形成治疗作用较生理盐水冲洗要好,差异有显著性(P<0.05);研究组治疗4周,总有效率为93.33%,对照组有效率为91.11%,差异无显著性(P>0.05)。结论:鼻渊通窍颗粒稀释液能够有效清洁术后的鼻腔,具有减轻鼻腔黏膜水肿、囊泡再生以及促进黏膜功能恢复等作用。     

Toxicology of 3-epi-deoxynivalenol,a deoxynivalenol-transformation product by Devosia mutans 17-2-E-8

Microbial detoxification of deoxynivalenol (DON) represents a new approach to treating DON-contaminated grains. A bacterium Devosia mutans 17-2-E-8 was capable of completely transforming DON into a major product 3-epi-DON and a minor product 3-keto-DON. Evaluation of toxicities of these DON-transformation products is an important part of hazard characterization prior to commercialization of the biotransformation application. Cytotoxicities of the products were demonstrated by two assays: a MTT bioassay assessing cell viability and a BrdU assay assessing DNA synthesis. Compared with DON, the IC₅₀ values of 3-epi-DON and 3-keto-DON were respectively 357 and 3.03 times higher in the MTT bioassay, and were respectively 1181 and 4.54 times higher in the BrdU bioassay. Toxicological effects of 14-day oral exposure of the B6C3F₁ mouse to DON and 3-epi-DON were also investigated. Overall, there were no differences between the control (free of toxin) and the 25 mg/kg bw/day or 100 mg/kg bw/day 3-epi-DON treatments in body and organ weights, hematology and organ histopathology. However, in mice exposed to DON (2 mg/kg bw/day), white blood cell numbers and serum immunoglobulin levels were altered relative to controls, and lesions were observed in adrenals, thymus, stomach, spleen and colon. Taken together, in vitro and in vivo studies indicate that 3-epi-DON is substantially less toxic than DON.     

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses

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HLA class II DQA and DQB epitopes: Recognition of the likely binding sites of HLA-DQ alloantibodies eluted from recombinant HLA-DQ single antigen cell lines

Donor-specific antibodies (DSA) in sera of sensitized transplant patients are often produced against the specific epitopes on mismatched HLA antigens. In this study, we selected sera from 30 kidney transplant patients with DSA and AMR to define DQ epitopes. Using adsorption and elution assays, we identified 18 antibody reaction patterns to define 6 new epitopes and to confirm 12 previously defined epitopes. In one patient case, one mismatched antigen produced 3 different antibodies and, in another, antibodies were produced against the alpha and beta chains of the same antigen. For some sera, a single epitope can explain reactions for 27 of the 29 DQ beads in the single antigen panel.     

3%氯化钠溶液对老年神经外科手术患者胸腔液体含量和血钠的影响

目的观察不同剂量3%氯化钠溶液对老年神经外科手术患者胸腔液体含量(TFC)和血钠的影响。方法 120例拟行择期神经外科开颅手术的老年患者,随机均分为3%氯化钠溶液2ml/kg组(H1组)、3%氯化钠溶液4ml/kg组(H2组)、3%氯化钠溶液6ml/kg组(H3组)和甘露醇组(M组)。H组所有患者在麻醉诱导后30min内分别给予3%氯化钠溶液2、4、6ml/kg;M组给予20%甘露醇250ml;其后输入复方乳酸钠5 ml·kg-1·h-1。用无创阻抗仪监测入室时(基础值,T0)、麻醉诱导后(T1)、切开硬脑膜(T2)和术毕(T3)时的MAP、HR、CO、TFC,同时记录PaO2、PaCO2、pH、Na+、K+血气分析,观察脑膜张力、出血量、尿量、手术时间和拔管时间。结果与T0时比较,T1~T3四组患者MAP明显降低(P0.05),T1四组CO明显降低(P0.05),而T2时H3组、M组和T3时H3组CO明显升高(P0.05),T2时H3组、M组和T3时H3组TFC明显升高(P0.05)。与M组比较,T3时H3组CO明显升高(P0.05),T2时H1组、H2组TFC明显降低、而H3组TFC明显升高(P0.05)。与T0时比较,T1~T3四组PaO2明显升高(P0.05),T2四组PaCO2明显降低(P0.05),T3时H2组和H3组Na+明显升高(P0.05)。与M组比较,T2时H3组、T3时H2组和H3组Na+浓度明显升高(P0.05)。与H3组比较,H1组、H2组和M组脑张力为良的例数明显增加(P0.05)。与M组比较,H1组、H2组、H3组尿量明显减少(P0.05)。结论甘露醇和高渗盐具有很好的稳定血流动力学和降低颅内压的作用,但是高渗盐可显著增加CO、TFC和Na+浓度,对老年患者具有增加心肺功能负担的风险,应该谨慎使用。     

Incidence of postoperative pain after use of calcium hydroxide mixed with normal saline or 0.2% chlorhexidine digluconate as intracanal medicament in the treatment of apical periodontitis

Objective

To compare the incidence of postoperative pain after the use of calcium hydroxide powder mixed with normal saline or 0.2% chlorhexidine digluconate as intracanal medicament.

Participants

Fifty-five subjects aged 17–60 years with teeth diagnosed to have apical periodontitis.

Intervention

Two-visit conventional root canal treatment of seventy teeth. The teeth were divided by randomization (balloting) into two groups: control group and experimental group, each with thirty-five teeth treated with calcium hydroxide mixed with normal saline or with 0.2% chlorhexidine digluconate as intracanal medicament respectively. Incidence of postoperative pain was assessed using the universal pain assessment tool and whether or not analgesic was taken.

Main outcome measured

Incidence of post-operative pain.

Result

Postoperative pain occurred only at 1-day and 1-week reviews. In the control group, the overall incidence of pain was the same at both review periods (5.7%), while the experimental group showed a slight decrease in incidence between 1-day (17.2%) and 1-week (11.4%) reviews. Incidence of flare-ups was more in the experimental group (11.4%) than in the control group (5.7%). No significant statistical differences between the two groups were observed (p > 0.05).

Conclusion

The incidence of postoperative pain was lower in the normal saline treatment group, but the difference was not statistically significant.     

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES:

Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid.

METHODS:

Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis.

RESULTS:

Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups.

CONCLUSIONS:

Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange.