The significance of serum xanthine oxidase and oxidation markers in acute paraquat poisoning in humans

ObjectivesDetermine xanthine oxidase (XO) activity and oxidative-stress parameters in human acute paraquat poisoning.Design and methodsTwnty-five patients and 26 healthy control participants were recruited. Serum XO, superoxide dismutase (SOD), Glutathione (GSH) and malondialdehyde (MDA) were determined by spectrophotometric methods.ResultsXO activity and MDA levels were higher and SOD activity and GSH level were lower in the patients group. XO activity and MDA level were significantly higher, and the GSH level and SOD activity were lower in the paraquat poisoning fatality group. There was a significant negative correlation between the XO activity and both the SOD and GSH, while there was a significant positive correlation between XO activity and the MDA level in the patients group.ConclusionsXO activity contributes to the development of oxidative injury in patients with paraquat poisoning. Serum XO activity could be used as a marker for prognosis in human acute paraquat intoxication.     

Identification of SAA and ACTB as potential biomarker of patients with severe HFMD using iTRAQ quantitative proteomics

Hand, foot and mouth disease (HFMD) is an infectious disease caused by a variety of enterovirus infections, and the most common types of virus infections are the newenterovirus71 (EV71) and coxsackievirus A group 16 (CoxA16). A small fraction of HFMD will cause further severe HFMD. A rapid and accurate diagnosis biomarker of severe HFMD is important for the timely treatment. In the study, we conducted a clinical biomarker discovery study using iTRAQ combined with MS. Serum proteome alterations in severe HFMD group (n = 32) and health control group (n = 32) were analyzed. 47 proteins were upregulated (fold change > 1.5) between the severe HFMD group and HC group. The identified proteins were classified into different groups according to the molecular function, biology processes, cellular component. During the up-regulated proteins, serum amyloid A (SAA) and human β-actin (ACTB), were confirmed in the serum of the severe HFMD and HC by ELISA assay. SAA and ACTB levels were significantly higher in the sever HFMD patients (P < .01), consistent with iTRAQ-LC-MS/MS analysis. In summary, Our results showed that SAA and human β-actin (ACTB) may be served as a potential biomarker of the clinical diagnosis of severe HFMD.     

Identification and confirmation of haptoglobin as a potential serum biomarker in hypertrophic cardiomyopathy using proteomic approaches

Abstract

Introduction. Aiming at identifying biomarkers for hypertrophic cardiomyopathy (HCM), the serum proteome was explored through a two-dimensional gel-based proteomic approach (2D-DIGE) coupled with mass spectrometry and database interrogation.

Methods. Serum samples from 20 male HCM patients and their sex- and age-matched controls were cleaned from interfering components. Patients and controls were pooled in five matched groups with the same age, and proteins extracts from each pool were labelled with cyanine dyes. Then, gel images were analysed using a fluorescence scanner and proteins were identified. Tryptic peptides were analysed by capillary reversed-phase liquid chromatography coupled online with tandem mass spectrometry (MS/MS).

Results. Four different proteins were observed to be differentially expressed between HCM patients and their matched controls. Of them, decreases in haptoglobin levels were confirmed to be associated with HCM in an independent set of 181 consecutive HCM patients from our monographic clinic and 114 controls with similar age and sex using a nephelometer-based technique. Moreover, a significant negative correlation was observed between haptoglobin and subaortic gradient, thus highlighting the role of haptoglobin in HCM.

Conclusion. All these observations point out the utility of the 2D-DIGE proteomic strategy for the identification of serum proteins indicative of the presence of cardiac injury.     

急性百草枯中毒的治疗进展

百草枯（paraquat,1,1-二甲基-4,4-联吡啶阳离子盐）,是目前应用最广泛的触灭型除草剂之一,动物属中等毒性,但对人的毒性却较高,成人估计致死量40mg／kg。百草枯中毒后可造成多个系统或器官损害,肺部最为严重,病死率极高,致病机制复杂且尚未完全明确,     

Pneumomediastinum predicts early mortality in acute paraquat poisoning

Abstract

Context. In paraquat (PQ) poisoning, death often occurs after the appearance of pneumomediastinum (PM). However, the clinical features and eventual outcome of PM in PQ intoxication remains unclear. Objective. We aimed to characterize PM following PQ poisoning and its prognostic value for predicting mortality. Materials and methods. Enrolled PQ-poisoned patients (n = 75) were divided into two groups according to whether PM could be detected by chest computed tomography or not. The study outcomes included 5- and 90-day death after intoxication. Survival curves were derived using the Kaplan–Meier method, and mortality risk factors were analyzed by forward stepwise Cox regression analysis. Results. PM was documented in 21.3% of the patients (16/75); in 13 of them PM set in within 3 days of PQ ingestion. 15 patients died within 3 days of appearance of PM. Compared with patients without PM, those with PM were younger (P = 0.011), and had higher scores of Acute Physiology and Chronic Health Evaluation (P < 0.001) and Sequential Organ Failure Assessment (P = 0.003). In addition, patients with PM had a higher incidence of acute renal failure (P = 0.001), toxic hepatitis (P = 0.008), and respiratory insufficiency (P = 0.003). PM predicted an increased risk of 90-day death (93.8% of patients with PM vs. 40.7% among those without PM; hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.0–5.6; P = 0.045), and increased risk of 5-day death (81.3% vs. 27.1%; HR, 3.2; 95% CI, 1.2–8.1; P = 0.017). Discussion and conclusion. Early PM, occurring within 8 days, is a specific predictor of mortality in PQ poisoning.     

Prediction of prognosis in acute paraquat poisoning using severity scoring system in emergency department

Objective. The aim of this study was to validate and compare the performance of serum paraquat level, severity index of paraquat poisoning (SIPP), Acute Physiology And Chronic Health Evaluation II (APACHE II), modified Simplified Acute Physiology Score II (MSAPS II), and modified Expanded Simplified Acute Physiology Score II (MSAPS IIe) calculated immediately after arrival on emergency department (ED) for assessing the mortality of acute paraquat poisoning. Methods. A retrospective study design was employed with the main outcome measure being mortality from year 2001 to 2010. MSAPS II and MSAPS IIe were employed in that assessment of the 24-hour urine output were not included. The performance of APACHE II, MSAPS II, MSAPS IIe, serum paraquat level and SIPP for prediction of mortality in acute paraquat poisoning were compared. Results. A total of 102 patients were enrolled in the study. The area under the ROC curve for APACHE II (0.800) was statistically lower than those for MSAPS II, MSAPS IIe, SIPP and serum paraquat (0.879, 0.893, 0.924,and 0.951, respectively). The Hosmer-Lemeshow goodness-of-fit test C statistic revealed that APACHE II, MSAPS II, MSAPS IIe and serum paraquat level showed good calibrations (chi-square 8.477 and p = 0.388, chi-square 4.614 and p = 0.798, chi-squared 5.301 and p = 0.725, chi-squared 1.009 and p = 0.985 respectively), but poor calibration for SIPP (chi-square 21.293 and p = 0.006). Conclusion. Serum paraquat level is still the most reliable prognosis factor in acute paraquat poisoning. But MSAPS II or MSAPS IIe calculated immediately after arrival on ED may be helpful to predict mortality in acute paraquat poisoning especially when hospital has no facility to measure serum paraquat level.     

Hemoperfusion using dual pulsatile pump in paraquat poisoning

Introduction

Hemoperfusion is an effective method for removing paraquat from the body. However, the need for special equipment and personnel to perform hemoperfusion limits its applicability in the emergency department. A portable, user-friendly extracorporeal life support system (Twin Pulse Life Support [T-PLS]) capable of producing dual pulsatile flow by an electromechanical blood pump has recently been developed. We compared the effects of hemoperfusion using traditional and dual-pulsatile pumps in a paraquat-intoxicated canine model. We hypothesized that T-PLS would be as effective as nonpulsatile hemoperfusion in reducing plasma and tissue paraquat levels.

Methods

Twelve adult male mongrel dogs were randomly assigned to hemoperfusion using a standard nonpulsatile pump (n = 6) or the T-PLS (n = 6). Paraquat intoxication was induced by intramuscular injection of paraquat (30 mg/kg). One hour after paraquat administration, hemoperfusion was performed for 4 hours at a flow rate of 125 mL/min. Periodic hemodynamic, chemical, and hematologic parameters as well as paraquat blood levels were obtained before and during the experiment. All animals were euthanized after completing 4 hours of hemoperfusion, and tissue levels of paraquat were determined.

Results

During hemoperfusion, hemodynamic parameters including aortic blood pressure, heart rate, rectal temperature, and Sao₂ showed no significant difference between the T-PLS group and the nonpulsatile pump groups. Chemical and hematologic parameters such as serum electrolytes, platelet level, creatinine concentration, the ratio of blood urea nitrogen (BUN) to creatinine, alanine aminotransferase/aspartate aminotransferase (ALS/AST) levels, and plasma hemoglobin concentration as an indicator of hemolysis also showed no between-group differences. Plasma paraquat concentrations and lung and kidney tissue paraquat concentrations were also similar in both groups.

Conclusions

In this experimental canine study, T-PLS was as effective as traditional nonpulsatile hemoperfusion in reducing plasma and tissues paraquat levels. There were also no differences in hemodynamic, chemical, and hematologic parameters between the groups. Hemoperfusion using T-PLS may play a role as an alternative method for treating patients with paraquat poisoning.     

血液灌流治疗急性百草枯中毒笔谈

急性百草枯（PQ）中毒的病死率极高,血液灌流（HP）作为PQ中毒救治的推荐方法,已经在我国得到了广泛应用,但对于HP强度以及是否合并血液透析等治疗方案目前仍无定论。最新的《2013百草枯诊治国内专家共识》推荐的方法,是HP时使用1个或多个灌流器、重复数次。而在临床实践中,临床医师多依据临床经验进行判断,随意性较大。本文就HP治疗PQ中毒的时机、模式、重复次数、以及其他合并治疗作一笔谈,以期对将来临床治疗和临床研究有所帮助。     

姜黄素治疗急性百草枯中毒的临床研究

目的:探讨姜黄素治疗急性百草枯口服中毒的临床疗效。方法:选择2007年3月-2010年3月在院救治的急性百草枯口服中毒患者74例,分为常规治疗组、激素治疗组和姜黄素治疗组。3组均常规对症治疗,激素治疗组在此基础上给予地塞米松25mg,静脉注射,每日1次。姜黄素治疗组在此基础之上给予姜黄素500mg/kg,口服,每日1次。在治疗第3天、7天、21天进行疗效评价,并对各组患者所出现的并发症进行统计。常规治疗组、激素治疗组和姜黄素治疗组均根据服毒量分组比较(20%原液或相当量<50ml组和≥50ml组)。结果:中毒治疗第3天,7天,21天,各组相比较,激素治疗组和姜黄素治疗组存活率均明显比常规治疗组高(均P<0.05),而姜黄素治疗组生存率与激素治疗组相比差异无统计学意义(P>0.05)。各组并发症发生率,即肺纤维化、急性肾功能衰竭、肝功能衰竭、MODS、DIC等并发症在激素治疗组和姜黄素治疗组均明显低于常规治疗组(均P<0.05),而激素治疗组与姜黄素治疗组之间比较差异无统计学意义(P>0.05)。结论:对急性百草枯口服中毒患者给予姜黄素治疗,其存活率和严重并发症发生率得到一定程度的改善,初步显示较好的疗效。     

急性百草枯中毒29例临床分析

目的：探讨百草枯中毒的临床特点及救治方法。方法：对29例急性百草枯中毒住院患者的临床资料进行回顾性分析。结果：所调查患者中,1例转院继续治疗,12例好转出院,11例死亡,5例未愈出院,院内死亡率40%。结论：百草枯毒性大,无特效解毒药。口服中毒后及早进行彻底洗胃、导泻等清除体内毒物,同时应用抗自由基药物、使用大剂量糖皮质激素减轻肺组织损害、尽早和反复予以血液净化治疗,上述综合有效的治疗是减少中毒死亡的关键。     

Evaluation of gastric lavage efficiency and utility using a rapid quantitative method in a swine paraquat poisoning model

BACKGROUND:Gastric lavage(GL)is one of the most critical early therapies for acute paraquat(PQ)poisoning;however,details of the treatment protocol remain to be established.METHODS:A rapid quantitative method involving sodium dithionite testing was developed.It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL,or without.The vital signs,laboratory testing,and PQ plasma concentrations were collected for therapeutic effect evaluation.RESULTS:The reaction conditions of the test were optimized for two types of samples.Early GL at one hour(H1)could improve the signs and symptoms after acute PQ poisoning at 24 hours(H24).In contrast,GL at 6 hours(H6)could only partially relieve the vital signs.The H1 GL group effectively reduced the peak of the plasma PQ concentration.In addition,the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24.Moreover,there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups.However,the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate.CONCLUSION:GL only at early stage may it benefit PQ poisoning in an animal model.The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate.The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.     

Identification of Cofilin‐1 as a novel biomarker of atopic dermatitis using iTRAQ quantitative proteomics

BackgroundAtopic dermatitis (AD) is a chronic relapsing inflammatory skin condition; however, little is known about the pathogenesis and serum biomarker of this disease.MethodsIsobaric tagging for relative and absolute quantitation (iTRAQ) proteomic assay was adopted to identify and quantify the differentially expressed proteins (DEPs) in the serum of AD patients. Bioinformatic analysis, including GO, Reactome, GSEA, PPI, and ssGSEA analysis, were used to identified the enriched pathways, hub proteins and immune cells. The expression level and distribution of hub proteins were confirmed by ELISA and IHC.ResultsSixty‐six DEPs were identified with iTRAQ proteomic assay by analyzing serum from AD patients and normal subjects. GO and Reactome analysis shown the alternated pathway were mainly involved in immunity, oxidative stress, and actin cytoskeleton. The GSEA and PPI network analysis among the DEPs were carried out and identified Cofilin‐1 and profilin‐1 as the core components of this network. Additionally, the disruption of Th1/Th2/Th17 cell balance and the significantly reducing of Treg, MDSC, and γδT cells was also found in AD patients using the ssGSEA analysis. Further ELISA and IHC assay validated the significantly elevated expression of Cofilin‐1 in AD patients.ConclusionOur results suggested that Cofilin‐1 may serve as a novel biomarker for AD diagnosis.     

Correction: iTRAQ-based quantitative proteomic analysis for identification of biomarkers associated with emodin against severe acute pancreatitis in rats

Correction for ‘iTRAQ-based quantitative proteomic analysis for identification of biomarkers associated with emodin against severe acute pancreatitis in rats’ by Hong Xiang et al., RSC Adv., 2016, 6, 72447–72457.

The authors regret that Fig. 2–4 were shown incorrectly in the original article. An incorrect section of the SAP group in the MPO-immunohistochemical staining (Fig. 2A) and HE staining (Fig. 3) experiments was used in error. In addition, Fig. 4 has been revised to show the zymogen granule, in order to better represent the ultrastructure of the pancreas. The correct versions of Fig. 2–4 are shown below.Open in a separate windowFig. 2Emodin down-regulated the MPO protein expression in pancreas of SAP rats. (A) Effect of emodin on MPO-immunopositive area (brown) staining of pancreatic tissue in SAP rats by immunohistochemical detection. (B) Effect of emodin on MPO-immunopositive area (red) staining of pancreatic tissue in SAP rats by immunofluorescence detection. Images are presented at 200× magnification. The data are presented as the mean ± SD, n = 6. **P < 0.01 versus SO; ^#P < 0.05 versus SAP, ^##P < 0.01 versus SAP.Open in a separate windowFig. 3Emodin improved pancreatic histopathology of SAP rats. Effect of emodin on H&E staining of pancreatic tissue in SAP rats. Images are presented at 200× magnification. The data are presented as the mean ± SD, n = 6. **P < 0.01 versus SO; ^#P < 0.05 versus SAP, ^##P < 0.01 versus SAP.Open in a separate windowFig. 4Emodin attenuated cellular structure changes in pancreas of SAP rats. Representative images of the cells’ ultrastructure in the SO (A), SAP (B), 60 mg kg⁻¹ emodin (C), 30 mg kg⁻¹ emodin (D) and 15 mg kg⁻¹ emodin (E) groups. Images are presented at 25 000× magnification.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

急性百草枯中毒患儿的综合救治与护理

目的:总结急性百草枯中毒患儿的救治与护理方法,为儿科临床工作提供借鉴和参考。方法:对我院2012年1月~2014年5月收治的89例急性百草枯中毒患儿的临床资料、治疗与护理措施进行回顾性分析和总结。结果:本组患儿救治成功73例,死亡1例,家属放弃治疗15例,最重要的死亡原因是急性肺损伤引起的肺纤维化。结论:通过对急性百草枯中毒患儿的综合救治与护理,达到了良好的治疗效果,但是由于国内尚无公认治疗指南,临床上应开展多中心、大样本研究以验证不同治疗方式的有效性。     

百草枯中毒致大鼠肺纤维化的实验研究

目的 探讨急性百草枯(PQ)中毒对大鼠肺纤维化的作用机制,为防治肺纤维化提供依据.方法 56只SD大鼠随机分为对照组和染毒组,染毒组32只,对照组24只,染毒组以4 mg/mL浓度的百草枯稀释溶液按14 mg/kg剂量一次性腹腔注射,对照组代以等剂量生理盐水注射.选取染毒组12只、对照组4只分别于第3、7、14、28天行活体肺组织Micro CT扫描,剩余大鼠分别于上述4 d每组各处死5只.处死剖胸后完整取出肺组织并观察整体肺的变化情况;称质量肺组织计算肺系数;通过HE染色观察肺组织的病理改变;测定肺组织匀浆中羟脯氨酸(HYP)的含量变化.结果 大鼠染毒后均出现行为异常;光镜及Micro CT观察肺组织可见随染毒时间的延长肺泡炎及肺纤维化征象相继发生;染毒组大鼠肺系数在各时间段皆高于相应对照组,差异有统计学意义(P<0.05或P<0.01),且染毒组内随染毒时间的延长肺系数亦显著升高(P<0.01);染毒组大鼠肺组织HYP含量在第7、14、28天时皆高于相应对照组,差异有统计学意义(P<0.01),且染毒组内随染毒时间的延长HYP含量亦显著增长(P<0.01).结论 百草枯中毒可导致大鼠肺组织发生纤维化,羟脯氨酸含量变化可判断纤维化程度,Micro CT可用于肺纤维化的检测.     

应用连二亚硫酸钠判断百草枯中毒的程度和预后

目的 应用连二亚硫酸钠显色法判断百草枯中毒的程度和预后.方法 将不同浓度的百草枯标准品与过量连二亚硫酸钠在碱性条件下反应,建立百草枯检测标准比色卡和标准曲线.应用连二亚硫酸钠显色法前瞻性检测浙江大学医学院附属第一医院2008年1月至2009年5月间收治的22例百草枯中毒患者血、尿液百草枯浓度,回顾性分析了患者就诊即刻血、尿百草枯浓度与患者预后的相关性.结果22例百草枯中毒患者经血液灌流、血浆置换和血液滤过治疗后随访3月以上,存活6例(27.3%).6例存活者就诊即刻百草枯半定量检测显示为极浅(3例)或浅(3例),16例死亡患者就诊即刻百草枯半定量检测显示为浅(1例)、中(2例)、深(2例)、极深(11例).6例存活患者与16例死亡患者就诊即刻尿百草枯质量浓度分别为(1.95±1.76)mg/L和(53.4±45.9)mg/L,P＜0.01.6例存活患者和13例死亡患者就诊即刻血清百草枯质量浓度分别为(1.70±1.39)ng/L和(29.5±22.1)mg/L,P＜0.01.22例百草枯中毒患者存活状况与就诊即刻尿百草枯半定量、定量检测结果 及血清百草枯质量浓度均显著相关(r_s分别为-0.804、-0.772,和-0.593,P＜0.01).结论 应用连二亚硫酸钠可迅速检测患者血、尿百草枯质量浓度,有助于了解患者中毒程度和判断预后.     

血液灌流救治急性百草枯中毒的疗效观察

目的：观察血液灌流（HP）治疗急性百草枯中毒的临床效果,探讨其价值。方法：百草枯中毒患者22例,分为HP组14例和非HP组8例,均给予常规0．9％氯化钠溶液洗胃、20％甘露醇导泻、补液、对症等综合治疗,HP组在此基础上尽早给予HP治疗,对比观察2组的治疗效果。结果：HP组痊愈率、总有效率明显高于非HP组,有统计学意义（P〈0．01）,中毒后6h内与6h后行HP者治愈率统计学意义（P〈0．01）;HP组ARDS和MOF发生率及病死率明显低于非HP组,有统计学意义（P〈0．01）,存活病例平均住院时间明显低于非HP组,死亡病例平均生存时间明显高于非HP组,有统计学意义（P〈0．01）。结论：HP是救治急性百草枯中毒的有效方法,尽早应用HP可明显提高急性百草枯中毒患者治愈率,降低死亡率、减少并发症,而且安全可靠,不良反应少。