血二胺氧化酶和 D-乳酸水平预测脑外伤病人发生急性胃肠损伤的临床价值

目的探讨二胺氧化酶( DAO)和 D-乳酸预测脑外伤病人发生急性胃肠损伤( AGI)的临床应用价值。方法选取 2019年 5月至 2021年 5月河北省人民医院收治的 129例脑外伤合并 AGI病人为研究对象,按照改良格拉斯哥昏迷量表( GCS)评分结合创伤性脑损伤临床分型标准,将病人分为轻度组( n=62)、中度组( n=32)和重度组( n=35);按照 AGI分级标准,分为 Ⅰ级 66例、 Ⅱ级 35例、 Ⅲ级 16例和 Ⅳ级 12例。采用酶联免疫吸附测定检测 DAO和 D-乳酸在病人血清中的表达水平; Pearson相关性分析探索 DAO与 D-乳酸表达水平的相关性;受试者操作特征曲线( ROC曲线)分析血清 DAO和 D-乳酸水平预测重度脑外伤合并 AGI病人的价值。结果轻、中、重度组脑外伤合并 AGI病人血清中 DAO(10.63±1.57,13.89±1.96,19.25±2.71)mg/L和 D-乳酸( 22.53±1.71,24.38±1.82,26.75±2.31)μg/L表达水平依次升高( P<0.05); Ⅰ级、 Ⅱ级、 Ⅲ级、 Ⅳ级脑外伤合并 AGI病人血清中 DAO(10.59±0.82,14.45±1.07,18.75±1.55,22.63±2.05)mg/L和 D-乳酸( 22.33±1.08,24.31±1.22,26.85±1.33,28.09±1.48)μg/L表达水平依次升高( P<0.05)。脑外伤合并 AGI病人血清中 DAO和 D-乳酸表达呈明显正相关( r=0.29,P<0.05); DAO和 D-乳酸与急性生理学和慢性健康状况评价 Ⅱ(APACHEⅡ)呈正相关,与 GCS评分呈负相关( P<0.05)。血清 DAO和 D-乳酸水平重度脑外伤合并 AGI的曲线下面积( AUC)分别为 0.98、0.90,二者联合预测的 AUC为 0.99高于单一指标检测。结论 DAO和 D-乳酸在脑外伤合并 AGI病人血清中表达水平与病情严重程度密切相关,二者联合检测对预测重度脑外伤合并 AGI具有较好的临床应用价值。     

血浆淀粉样蛋白A和硫化氢水平对脓毒症休克病人诊断及预后价值

目的探讨血浆淀粉样蛋白 A(SAA)和硫化氢水平对脓毒症休克病人诊断及预后的评估价值。方法选取 2015年 3月至 2017年 4月在河南科技大学第一附属医院经医学确诊的 124例脓毒症休克病人作为研究组,同时选取在该院体检正常者 124例作为对照组。采用酶联免疫双抗体夹心法检测研究组和对照组血浆 SAA水平;利用分光光度法检测所有研究对象血浆硫化氢水平;术后 1个月,对脓毒症休克病人进行随访,根据病人生存情况分为预后良好组和预后不良组,比较两组血浆 SAA、硫化氢水平;绘制受试者工作特征曲线( ROC)评估血浆 SAA、硫化氢水平对脓毒症休克病人治疗预后不良的诊断价值;对不同预后脓毒症休克病人的临床资料进行比较; logistic回归分析脓毒症休克预后的影响因素。结果脓毒症休克组病人血浆 SAA、硫化氢水平明显高于对照组［(128.35±41.23)μmoL/L比( 7.82±2.24)μmoL/L,t＝32.505,P＜0.001;(104.47±31.98)μmoL/L比( 45.15±14.27)μmoL/L,t＝18.863,P＜0.001］;预后不良组血浆 SAA、硫化氢水平明显高于预后良好组［(158.97±42.23)μmoL/L比( 107.83±33.59)μmoL/L,t＝7.465,P＜0.001(127.35±34.99)μmoL/L比( 89.62±26.52)μmoL/L,t＝6.399,P＜0.001］;血浆 SAA、硫化氢水平预测病人系统治疗 1个月后不良预后的曲线下面积( AUC)分别为 0.812、0.788,其对应截断值分别为 132.45 μmoL/L、110.03 μmoL/L,其对应灵敏度分别为 75.0%、72.9%,对应特异度分别为 78.9%、81.6%;两者联合评估脓毒症休克的 AUC为 0.913,其灵敏度、特异度分别为 82.3%、93.4%;预后不良组脓毒症休克病人中具有肝硬化史、糖尿病史、白血病史、吸烟史者比例,急性生理学与慢性健康状况评分系统 Ⅱ(APACHEⅡ)评分,序贯器官功能衰竭评分( SOFA)及乳酸含量均明显高于预后良好组( P＜0.05);肝硬化、白血病、 APACHEⅡ评分、 SOFA评分、 SAA、硫化氢为脓毒症休克预后的危,险因素( P＜0.05)。结论血浆 SAA、硫化氢水平在脓毒症休克病人中呈高表达,两者可能对脓毒症休克病人的早期诊断及预后有一定的评估价值。     

降钙素原与C-反应蛋白对严重脓毒症和脓毒性休克患者严重程度的评估价值

目的探讨降钙素原(PCT)与C-反应蛋白(CRP)对重症监护病房(ICU)严重脓毒症和脓毒性休克患者严重程度的评估价值以及与急性生理学与慢性健康状况评分系统Ⅱ评分(APPACHEⅡ评分)及序贯器官衰竭评分(SOFA评分)的相关性。方法对2013年1月至2015年1月收住大同市第五人民医院重症医学科的104例脓毒症患者根据是否休克分为2组:脓毒性休克组(51例)和严重脓毒症组(53例)。2组患者在入住ICU后收集性别、年龄、既往史,急查血常规、即刻血糖、血气分析、肝肾功能,细菌培养,APPACHEⅡ评分及SOFA评分。入科24 h内抽血化验降钙素原、C-反应蛋白。观察2组患者PCT、CRP、SOFA评分、APACHEⅡ评分差异,脓毒症患者PCT、CRP与SOFA评分、APACHEⅡ评分的相关性,绘制受试者工作曲线(ROC),评价PCT、CRP、SOFA评分和APACHEⅡ评分对不同程度脓毒症的诊断价值。结果脓毒性休克组严重脓毒症PCT[(24.3±5.7)ng/ml和(4.2±2.6)ng/ml,P<0.01]、CRP[(97.1±10.8)mg/L和(64.2±11.3)mg/L,P<0.05)]、APACHEⅡ评分[(20.9±7.1)分和(16.3±5.7)分,P<0.01]、SOFA评分[(10.6±4.1)分和(5.4±3.0)分,P<0.05)]与严重服毒症组比较,脓毒性休克组各指标均明显升高。PCT、CRP与SOFA评分呈显著正相关(PCT:r=0.531,P<0.01。CRP:r=0.426,P<0.01),而二者与APACHEⅡ评分均无相关性(PCT:r=0.032,P>0.05;CRP:r=0.05,P>0.05)。PCT对评价脓毒症严重程度的ROC曲线下面积(AUC)明显大于CRP的AUC[0.787(95%可信区间0.679,0.894);0.671(95%可信区间0.546,0.796)]及APACHEⅡ评分的AUC[0.787(95%可信区间0.679,0.894);0.687(95%可信区间0.562,0.812)]。PCT对脓毒症严重程度评估的敏感度及特异性均高(截断值在0.795 ng/ml时,敏感度88.6%,特异度63.9%)。CRP的敏感度高但特异性低(截断值为35.00 mg/L时,敏感度88.6%,特异性41.7%)。SOFA评分的特异性高但敏感度低(截断值在9.00分时,敏感度65.7%,特异性91.7%)。APACHEⅡ评分敏感度高及特异性比PCT低(截断值为18.5分时,敏感度74.3%,特异度58.3%)。结论 PCT与CRP水平能很好地反映脓毒症患者的严重程度,且与SOFA评分有良好的相关性,PCT对脓毒症患者严重程度的评估,敏感性特异性均高。     

血清肝素结合蛋白、炎性蛋白、前肾上腺髓质素对中心静脉导管相关性感染预后的预测价值

目的探讨血清肝素结合蛋白( HBP)、炎性蛋白( hs-CRP)、前肾上腺髓质素( pro-ADM)表达对中心静脉导管相关性感染( Cvc-Ri)预后的影响和预测价值。方法选取 2016年 8月至 2019年 5月资阳市第一人民医院 Cvc-Ri病人 112例作为对象,根据 28 d预后情况分为生存组( 70例)、死亡组( 42例)。比较两组血清 HBP、hs-CRP、pro-ADM水平及急性生理和慢性健康(APACHEⅡ)评分、全身感染相关性器官功能衰竭评价系统( SOFA)评分, Pearson相关性分析各血清指标与 APACHEⅡ、SOFA评分相关性,受试者工作特征( ROC)曲线分析血清 HBP、hs-CRP、pro-ADM对 Cvc-Ri预后的预测价值,并对比不同血清因子水平病人生存状况,分析其对预后的影响关系。结果确诊第 5天生存组血清 HBP水平( 27.32±11.37)μg/L、hs-CRP水平( 75.13±28.09)mg/L、pro-ADM水平( 2.40±0.80)nmol/L、APACHEⅡ评分( 13.50±3.06)分、 SOFA评分( 5.10±1.14)分低于死亡组( 41.54±     

血管内皮生长因子、降钙素原、白细胞介素-18 对急性创伤病人呼吸衰竭的预测价值

目的观察急性创伤合并呼吸衰竭病人的血管内皮生长因子(VEGF)、降钙素原(PCT)、白细胞介素-18(IL-18)水平,探讨三者对急性创伤病人呼吸衰竭的预测价值。方法回顾性分析2018年1月至2019年12月于自贡市第一人民医院住院治疗的急性创伤合并呼吸衰竭病人70例的临床资料,根据其转归分为好转组(60例)和死亡组(10例)。比较好转组和死亡组病人VEGF、PCT、IL-18、血气指标、急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分的差异,分析急性创伤病人PCT、VEGF、IL-18指标与血气指标、APACHEⅡ评分的相关性。结果好转组VEGF［(126.36±15.78)ng/L比(138.27±17.64)ng/L］、PCT［(3.22±0.78)mg/L比(4.24±1.30)mg/L］、IL-18［(136.74±23.09)ng/L比(195.64±36.13)ng/L］水平均低于死亡组,差异有统计学意义(P<0.05);好转组病人氧饱和度(SO₂)［(56.28±6.39)%比(41.64±8.15)%］、氧分压(PaO₂)［(99.02±0.28)mmHg比(95.36±0.28)mmHg］、氧合指数(PaO₂/FiO₂)［(215.47±37.53)比(176.47±36.25)］水平均高于死亡组、死亡组病人APACHEⅡ评分高于好转组［(19.45±2.42)分比(22.00±2.45)分］,差异有统计学意义(P<0.05);急性创伤病人的PCT、VEGF、IL-18水平与SO₂、PaO₂、PaO₂/FiO₂水平呈负相关,与APACHEⅡ评分呈正相关,差异有统计学意义(P<0.05)。结论急性创伤合并呼吸衰竭病人的PCT、VEGF、IL-18水平较高,PCT、VEGF、IL-18可反映急性创伤并呼吸衰竭病人的病情程度,三者表达水平越高,可能提示呼吸功能损伤越严重,呼吸衰竭越明显,病情越危重,预后越差。     

脓毒症患者早期血小板减少对预后的预测价值

目的 探讨脓毒症患者早期发生血小板(Plt)减少对预后的预测价值。方法 回顾性分析334例脓毒症患者的临床资料,依据入ICU 28 d内的生存情况分为死亡组(72例)和存活组(262例)。比较两组的相关资料。采用多因素logistic回归分析脓毒症患者死亡的危险因素,绘制ROC曲线评估Plt减少、急性生理与慢性健康评估Ⅱ(APACHEⅡ)评分、序贯器官衰竭估计(SOFA)评分和血乳酸对预后的预测价值。结果 与存活组相比,死亡组年龄大,入ICU 24 h时的血乳酸、降钙素原(PCT)、SCr水平、APACHEⅡ评分和SOFA评分升高,而氧合指数和第7天Plt计数降低(P<0.05)。Plt减少以及APACHEⅡ评分、SOFA评分、血乳酸水平升高是脓毒症患者死亡的独立危险因素。Plt减少、APACHEⅡ评分、SOFA评分和血乳酸水平预测脓毒症死亡的AUC分别为0.819、0.857、0.848和0.859(P<0.01)。Plt减少的约登指数为0.638,其预测脓毒症死亡的灵敏度为91.67%,特异度为72.14%。结论 脓毒症患者早期1周内发生Plt减少,对预后有较高的预测价...     

多项炎症因子联合监测对细菌性脓毒症的辅助诊断作用

目的 研究多项炎症因子联合监测对细菌性脓毒症的辅助诊断作用。 方法 回顾性分析2014年1月至2016年12月于承德医学院附属医院接受治疗的细菌性脓毒症病人80例为研究对象,根据病人感染情况不同分为革兰阳性菌脓毒组48例、革兰阴性菌脓毒症组32例。另取同期接受体检的健康人30例为健康对照组。分别采用免疫发光分析法、免疫速率散射比浊法以及酶联免疫吸附法检测各组血清降钙素原(PCT)、C反应蛋白(CRP)、白细胞介素-27(IL-27)水平,同时计算急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)与序贯器官衰竭估计(SOFA)评分。比较三组血清学指标水平以及APACHEⅡ、SOFA评分,并作相关性分析。另外,将细菌性脓毒症病人根据治疗后生存状况分为死亡组与存活组,比较两组病人血清PCT、CRP、IL-27水平及APACHEⅡ、SOFA评分。并作多因素Logistic回归分析。 结果 革兰阴性菌脓毒症组血清PCT、CRP、IL-27水平以及APACHEⅡ、SOFA评分明显高于革兰阳性菌脓毒症组,而革兰阳性菌脓毒症组明显高于健康对照组(均P＜0.05)。经Preason相关性分析可得:脓毒症病人血清PCT、CRP、IL-27水平与APACHEⅡ、SOFA评分均呈正相关(均P＜0.05)。死亡组血清PCT、IL-27、CRP水平与APACHEⅡ、SOFA评分均明显高于存活组(均P＜0.05)。经多因素logistic回归分析可得:PCT、CRP、IL-27以及APACHEⅡ评分均为影响细菌性脓毒症病人预后的独立危险因素(均P＜0.05)。 结论 联合检测血清PCT、CRP、IL-27水平以及计算APACHEⅡ、SOFA评分可诊断细菌性脓毒症,并可有效评估病人预后。     

红细胞分布宽度在脓毒性休克患者中的变化研究

目的 观察红细胞分布宽度(RDW)在脓毒性休克患者中的变化情况及其临床应用价值。 方法 将研究对象分为脓毒性休克组(脓毒性休克组又分为死亡组和存活组)、脓毒症组和健康对照组,观察各组患者的RDW水平,同时与C反应蛋白(CRP)、降钙素原(PCT)、动脉血乳酸(Lac)、急性生理与慢性健康评分(APACHEⅡ)和序贯器官衰竭估计评分(SOFA)等进行相关性分析。 结果 脓毒性休克组、脓毒症组患者RDW明显高于健康对照组(P＜0.05)。与存活组相比,死亡组入院后1、3、5、7、10 d的RDW升高(P＜0.05)。入院第1个24 h脓毒性休克组RDW与CRP、PCT、APACHEⅡ评分和SOFA评分成正相关性(r=0.836,0.683,0.589,0.727,0.311,P＜0.05)。RDW与APACHEⅡ评分和SOFA评分联合可以提高脓毒性休克患者的死亡预测能力。 结论 RDW水平升高对脓毒症具有预示作用,同时对脓毒性休克患者不良预后具有判断作用。     

改良版危重症营养风险评分对脓毒症病人发生持续炎症 -免疫抑制 -分解代谢综合征的预测价值

目的探讨改良版危重症营养风险( mNUTRIC)评分对脓毒症病人发生持续炎症 -免疫抑制 -分解代谢综合征( PICS)的预测价值。方法纳入 2021年 1月至 2022年 8月在海南医学院第二附属医院重症监护病房(ICU)接受治疗的 285例脓毒症病人为研究对象。收集病人入 ICU时的年龄、查尔森合并症指数评分、急性生理学与慢性健康状况评价 Ⅱ(APACHE Ⅱ)评分、贯器官衰竭估计( SOFA)评分、 mNUTRIC评分以及实验室指标和器官功能支持治疗情况。根据是否发生 PICS将病人分为序PICS组( n=102)与非 PICS组( n=183)比较两组间各指标的差异。应用二分类 logistic回归模型和受试者操作特征( ROC)曲线分析 mNUTRIC评分与脓毒症病人发生,PICS的关系。结果脓毒症病人 PICS发生率为 35.79%。PICS组年龄、查尔森合并症指数评分、 APACHEⅡ评分、 SOFA评分、 mNUTRIC评分、应用血管活性药物时间 ≥72 h占比、机械通气时间 ≥72 h占比、连续肾脏替代治疗( CRRT)时间 ≥72 h占比以及血清 C-反应蛋白、乳酸水平分别为( 73.49±8.64)岁、［2.00(1.00,3.00)］分、(21.67±6.62)分、(8.69±2.63)分、［5.00(5.00,6.00)］分、 53.92%、71.57%、48.04%、［32.85(20.83,74.98)］ mg/L、［3.33(2.30,4.78)］ mmol/L,均高于非 PICS组的( 67.72±8.63)岁、［1.00(0.00,2.00)］分、(17.83±6.05)分、(7.45±2.43)分、［3.00(2.00,4.00)］分、 29.51%、41.53%、23.50%、［27.00(18.50,38.30)］ mg/L、［2.60(2.02,4.00)］ mmol/L,差异有统计学意义( P<0.05)。 PICS组的血清白蛋白水平为(37.17±2.92)g/L,低于非 PICS组的( 38.22±2.88)g/L,差异有统计学意义( P<0.05)。 mNUTRIC评分 ≥5分的脓毒症病人 PICS发生率为 73.64%,高于 mNUTRIC评分 <5分的 12.00%(χ2=111.66,P<0.001)。 logistic回归分析结果显示, mNUTRIC评分值升高［OR=2.61,95％CI:(1.73,3.94)P<0.001］机械通气时间 ≥72 h［OR=3.24,95％CI:(1.60,6.56)P=0.001］、 CRRT时间 ≥72 h［OR=3.45,95％CI:(1.68,7.08)症病人发生 PICS的独立危险因素。 mNUTRIC预测脓毒症病人发生 PICS的 ROC曲线下面积为 0.85, CI:(0.81,0.89)最佳截断值为 4分时,预测脓毒症病人发生 PICS的灵敏度为 79.41%、特异度为 P=0.00,1］是脓毒,评分,95%,84.15%和约登指数为 0.64。结论发生 PICS脓毒症病人入 ICU时 mNUTRIC评分明显高于非 PICS病人,同时 mNUTRIC评的,分是脓毒症病人发生 PICS的独立预测因子,并且 mNUTRIC评分在预测脓毒症病人 PICS方面具有更好的区分能力。     

血浆血管生成素?2、白细胞介素?8在重症社区获得性肺炎疾病严重程度及其预后评估中的价值

目的探讨血浆内血管生成素 ?2(Ang?2)、白细胞介素 ?8(IL?8)与重症社区获得性肺炎( SCAP)病人疾病严重程度及其预后的价值。方法收集 2016年 1月 1日至 2018年 8月 31日合肥市第二人民医院重症医学科( ICU)收治的 SCAP病人 68例,别检测病人的 C反应蛋白( CRP)、 IL?8、血浆 Ang?2水平,进行急性生理与慢性健康评分( APACHEⅡ)和氧合指数( PO₂/FiO₂)记分录,根据 28 d转归结果将其中纳入标准的 65例 SCAP病人(另外 3例近亲属中途放弃治疗而退出)分为存活组( 35人)及死亡组(30人)。结果死亡组病人 CRP［(147.99±55.94)mg/L比( 108.59±48.19)mg/L,t＝3.051,P＝0.003］、 APACHEⅡ评分［(25.47±     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.