银杏叶提取物对氯化镉损伤人肾近曲小管细胞的保护作用实验研究

目的探讨银杏叶提取物对氯化镉所致人肾近曲小管细胞损伤的保护作用及其保护机制。方法体外培养人肾近曲小管细胞系HK-2细胞,以氯化镉处理细胞建立损伤模型。设对照组(仅细胞)、1个单染镉组(40μmol/L)、3个银杏叶提取物干预组(40μmol/L氯化镉+28μg/ml银杏叶提取物、40μmol/L氯化镉+56μg/ml银杏叶提取物、40μmol/L氯化镉+84μg/ml银杏叶提取物),共同处理HK-2细胞24小时,噻唑蓝比色法(MTT)检测HK-2细胞活力,流式细胞术检测HK-2细胞凋亡,试剂盒检测HK-细胞内活性氧水平、脂质过氧化产物丙二醛含量,逆转录聚合酶链反应法(RT-PCR)检测细胞凋亡相关因子p53、Bax、Bcl-2 mRNA基因表达水平。结果 (1)与对照组相比,氯化镉单独处理组HK-2细胞存活率降低(P0.01),早期凋亡率上升(P0.05),细胞内活性氧、丙二醛含量升高(P0.05),细胞内p53、BaxmRNA基因的表达水平上升(P0.05),细胞内Bcl-2 mRNA基因表达水平下降(P0.05);(2)与氯化镉单独处理组相比,56μg/ml、84μg/ml银杏叶提取物干预组HK-2细胞存活率上升(P0.05),细胞凋亡率下降(P0.05),细胞内活性氧、丙二醛含量降低(P0.05),细胞内p53、Bax基因表达水平下降(P0.05),Bcl-2基因表达水平上升(P0.05)。结论 56μg/ml～84μg/ml银杏叶提取物对氯化镉所致的人肾近曲小管细胞生长抑制、细胞凋亡有保护作用,其保护作用机制与抗氧化应激有关。     

乌司他丁对百草枯诱导HK-2细胞损伤的保护作用及机制

目的 探讨乌司他丁(ulinastatin,UTD对百草枯(paraquat,PQ)诱导HK-2细胞损伤的保护作用及机制研究.方法 常规培养HK-2细胞,分为正常对照组、PQ组、UTI+PQ组、UTI对照组,应用CCK-8法检测细胞存活率,高效液相色谱法(HPLC)法检测细胞内PQ浓度,DCFH-DA染色法检测细胞内活性氧(ROS)含量,化学比色法检测细胞内超氧化物歧化酶(SOD)、丙二醛(MDA)含量,双抗夹心酶联免疫吸附法(ELISA)法检测细胞上清液中白细胞介素(IL-6)、肿瘤坏死因子(TNF-α)水平.结果 200 μmol/L PQ即能显著抑制HK-2细胞增殖,并且其抑制作用呈浓度和时间依赖性;8 000 U/ml以下UTI对HK-2细胞仍无明显抑制作用.与PQ组比较,UTI+PQ组随着UTI浓度的增加,细胞抑制率明显减轻,差异有统计学意义(P＜0.05).与同时间PQ组比较,UTI+PQ组HK-2细胞内PQ浓度明显下降,除6h组外,差异均有统计学意义(P＜0.05).与空白对照组相比较,PQ组HK-2细胞内SOD活力明显降低,ROS、MDA水平明显升高,差异有统计学意义(P＜0.05);与PQ组比较,UTI+PQ组细胞内SOD活力明显升高,ROS、MDA水平明显降低,差异有统计学意义(P＜0.05).与空白对照组比较,PQ组细胞上清中IL-6、TNF-α.水平明显升高,差异有统计学意义(P＜0.05);与PQ组比较,UTI+PQ组细胞上清中IL-6、TNF-α水平明显降低,差异有统计学意义(P＜0.05).结论 UTI可通过减少HK-2细胞内的PQ的蓄积来减轻PQ对HK-2细胞的氧化损伤及炎症损伤.     

叔丁基对苯二酚对百草枯神经细胞毒性和氧化应激的拮抗作用

目的 研究叔丁基对苯二酚(tBHQ)预处理对百草枯(PQ)致大鼠肾上腺嗜铬细胞瘤(PC12)细胞毒性和氧化应激的拮抗作用.方法 将PC12细胞分为溶剂对照组及100、300 μmol PQ处理组.用终浓度为40 μmol/LtBHQ预处理PC12细胞4 h再分别用终浓度0、100、300 μmol/L PQ处理细胞24或48 h,用噻唑蓝(MTT)法检测细胞毒性,用Annexin V-FITC/PI法流式细胞仪(FCM)检测细胞凋亡,用硫代巴比妥酸法测定细胞丙二醛(MDA)含量.结果 用40μmol/LtBHQ预处理后再用100、300μ,mol/L PQ处理PC12细胞24 h细胞存活率分别较100、300 μmol/L PQ组增高,差异有统计学意义(P＜0.05,P＜0.01);用40μmol/LtBHQ预处理后再用100μmol/LPQ处理PC12细胞48 h细胞存活率较100μmol/LPQ处理组细胞存活率增高,差异有统计学意义(P＜0.01);用40μmol/LtBHQ预处理后再用100、300μmol/PQ处理PC12细胞24 h后,细胞凋亡率分别较100、300 μmol/L PQ下降,差异有统计学意义(P＜0.05,P＜0.01);用40μmol/LtBHQ预处理后再用100、300μmol/LPQ处理PC12细胞24 h后,MDA含量分别较100、300 μmol/L PQ组下降,MDA含量分别为相应对照组的0.61、0.57倍,差异有统计学意义(P＜0.05).结论 tBHQ预处理可削弱PQ致PC12细胞的细胞毒性、细胞凋亡以及氧化应激作用.

Abstract：

Objective To investigate the protective effects of the tert-butylhydroquinone (tBHQ)pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells. Methods Cytoyoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 μmol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 μmol/L tBHQ for 4 h, PC 12 cells were exposed to PQ at the doses of 0, 100, 300 μmol/L for 24 h and 48 h, respectively.The viability of PC 12 cells was measured by MTT assay, the apoptosis rates of PC 12 cells were detected by flow cytometry (FCM) and the malondialdehyde (MDA) levels of PC 12 cells were examine by thiobarbituric acid (TBA) method. Results When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the viability of PC 12 cells pretreated with tBHQ was significantly higher than that of PC 12 cells only exposed to PQ (P＜0.05 or P＜0.01). When the exposure dose of PQ was 100μmol/L for 48 h, the viability of PC12 cells pretreated with tBHQ was significantly higher than that of PC12 cells only exposed to PQ (P＜0.01). When the exposure doses of PQ were 100 and 300 μmol/L for 24 h, the apoptosis rates and MDA levels of PC12 cells pretreated with tBHQ were significantly lower than those of PC12 cells only exposed to PQ (P＜0.05 or P＜0.01). Conclusions tBHQ preteatment can reduce the cytotoxicity, apoptosis and oxidative stress induced by PQ in PC12 cells.     

肝细胞生长因子对铅致人肾小球系膜细胞损伤的保护效应的机制

目的初步探讨肝细胞生长因子（HGF）防护铅处理致人肾小球系膜细胞（HMC）损伤的作用机制。方法将HMC分为对照组（C组）、Pb10μmol／L组和HGF＋Pb10μmol／L组,在6、12、24、48h分别通过噻唑蓝（MTY）法检测细胞存活率和用流式细胞仪检测凋亡率;实时荧光定量一PCR检测各组细胞中Caspase-3的表达水平。结果MTr检测结果显示。Pb10pμmol／L组HMC在6、12、24、48h细胞生长存活率均显著低于HGF＋Pb10μmol／L组（P〈0．01）;流式凋亡检测结果显示,HMC在10μmol／L醋酸铅染毒6、12、24和48h后,HGF＋Pb10μmol／L组在各个时间点细胞凋亡率显著低于Pb10μmol／L组（P〈0．01）。实时荧光定量-PCR检测结果显示,在HMC铅染毒48h后,HGF＋Pb10μmol／L组Caspase-3的表达量显著低于Pb10μmol／L组（P〈0．01）。结论铅促进HMC细胞的凋亡,而HGF通过降低Caspase．3的表达抑制HMC的凋亡,从而发挥对铅致HMC细胞损伤的保护作用。     

N-乙酰半胱氨酸对镉致人胚肾细胞凋亡拮抗作用

目的探讨N-乙酰半胱氨酸（N-acetyl cysteine,NAC）对氯化镉所致人胚肾（human embryonic kidney,HEK）细胞凋亡的拮抗作用。方法应用四甲基偶氮噻唑蓝（MTT）比色法和流式细胞术（flowcytometry,FCM）检测不同CdCl2浓度（0,10,20,40,80μmol/L）处理以及不同浓度NAC（1,2,4,8mmol/L）和镉联合作用对HEK细胞相对存活率和凋亡率的影响。结果单纯染镉时,与对照组（0μmol/L）比较,20,40,80μmol/L CdCl23组HEK细胞相对存活率明显降低（P〈0.01）,HEK细胞凋亡率明显升高（P〈0.01）;NAC与镉联合作用时,与40μmol/L CdCl2比较,40μmol/L CdCl2＋4,8 mmol/L NAC2组HEK细胞相对存活率明显提高,40μmol/L CdCl2＋2,4,8 mmol/L NAC3组HEK细胞凋亡率明显降低。结论一定浓度氯化镉可引起HEK细胞凋亡增加,NAC可以拮氯化镉引起的细胞凋亡。     

全反式维甲酸对高糖诱导HK-2细胞FN、LN表达的影响

目的观察全反式维甲酸（ATRA）对高糖诱导人肾小管上皮细胞（HK-2）纤维连接蛋白（FN）、层粘连蛋白（LN）表达的影响,探讨ATRA延缓糖尿病肾病肾间质纤维化的发生机制。方法体外培养的HK-2细胞随机分为正常对照组（NG组,含5.5mmol/LD-glucose）;高糖组（HG组,含30mmol/LD-glucose）;渗透压对照组（MG组,含5.5mmol/LD-glucose＋24.5mmol/Lmannitol）;全反式维甲酸低浓度组（ATRA1组,HG＋10^-7mol/LATRA）;全反式维甲酸中浓度组（ATRA2组,HG＋10^-6mol/LATRA）;全反式维甲酸高浓度组（ATRA3组,HG＋10^-5mol/LATRA）;药物溶剂无水乙醇组（HG＋10^-2mol/L无水乙醇）;卡托普利组（HG＋10^-5mol/Lcaptopril）。各组细胞分别培养24h、48h和72h后收集细胞上清液。采用酶联免疫吸附法（ELISA）检测培养细胞上清液FN、LN的浓度。结果高糖可增加HK-2细胞培养上清的FN、LN的水平（P〈0.01）,ATRA可以部分抑制高糖的作用（P〈0.01）。结论高糖可以促进体外培养的HK-2细胞FN、LN的表达,ATRA可以抑制高糖的作用,这可能是ATRA延缓糖尿病肾病肾间质纤维化进展的机制之一。     

AMPK-mTOK信号通路参与百草枯致PC12细胞的自噬抑制作用

目的探讨AMPK-mTOR信号转导通路在百草枯(paraquat,PQ)诱导大鼠肾上腺髓质嗜铬细胞瘤细胞(PC12)自噬异常中的调控作用。方法用终浓度0、25、50、100、200、300、400 μmol/L PQ处理PC12细胞24 h,300 μmol/L PQ处理细胞不同时间(6、12、24、48 h),四甲基偶氮唑蓝(MTT)检测细胞相对存活率,确定剂量/时间-效应关系;终浓度0、100、200、300 μmol/L PQ处理细胞24 h,分光光度法检测培养上清中乳酸脱氢酶(LDH)活力;二氯荧光素双醋酸盐(DCFH-DA)法检测细胞内活性氧(ROS)水平;单丹磺酰尸胺(MDC)染色法观察自噬溶酶体的表达及分布变化;免疫荧光(IF)检测微管相关蛋白1轻链3(LC3)表达水平;免疫印迹法(Western blot)检测自噬相关蛋白LC3Ⅱ、p62、Beclin1及AMPK-mTOR信号通路蛋白p-AMPK、p-mTOR表达水平。结果与对照组比较,100、200、300、400 μmol/L PQ染毒组的细胞存活率明显降低,且呈剂量依赖关系,差异有统计学意义(P<0.05)。300 μmol/L PQ处理细胞不同时间(6、12、24、48 h),细胞存活率随染毒时间的延长而下降,其中12、24、48 h染毒组的差异有统计学意义(P<0.05)。与对照组比较,100、200、300 μmol/L PQ染毒组细胞上清液中LDH活力明显升高,细胞内ROS荧光强度明显增高,差异有统计学意义(P<0.05);MDC染色结果显示,PQ染毒组的自噬溶酶体在核周分布密度降低、荧光强度减弱、自噬水平降低;免疫荧光结果显示,PQ染毒组的LC3荧光强度减弱,细胞自噬水平下降,与MDC染色结果一致。Western blot结果显示,与对照组比较,PQ染毒组的自噬相关蛋白LC3Ⅱ、Beclin1表达水平均明显降低,而p62蛋白表达水平升高,差异有统计学意义(P<0.05)。200、300 μmol/L PQ染毒组的p-AMPK蛋白表达水平降低,p-mTOR蛋白表达水平升高,差异有统计学意义(P<0.05)。结论PQ致PC12细胞损伤过程中,细胞自噬水平降低,AMPK-mTOR信号通路发挥调节作用。     

槲皮素对百草枯染毒肺上皮细胞存活率和上皮间质转化标志的影响

  目的  探讨槲皮素（Que）对百草枯（PQ）处理肺上皮细胞（MLE-12）的存活率和上皮间质转化（epithelial-mesenchymal transition，EMT）的影响及机制。
  方法  采用CCK-8法分别检测不同剂量PQ（50、150、450 μmol/L）对MLE-12细胞存活率的影响。实验设立空白对照组、阳性对照组、PQ（150 μmol/L）+Que（30、60、90μmol/L）干预组、阴性对照组，在Que干预24 h后检测细胞存活率。应用荧光定量PCR法和蛋白免疫印迹（Western blot）法分别检测α-SMA、结缔组织生长因子（connective tissue growth factor，CTGF）、E-Cadherin、TGF-β1、Smad3、Akt、mTOR的mRNA和蛋白表达。
  结果  经PQ（150 μmol/L）处理后，60 μmol/L和90 μmol/L的Que能够显著提高MLE-12细胞存活率，与阳性对照组比较差异有统计学意义（P < 0.05）。荧光定量PCR法和Western blot法检测结果表明，与空白对照组比较，50 μmol/L的PQ能提高α-SMA、CTGF、E-Cadherin、TGF-β1、Smad3、Akt、mTOR的mRNA表达，以及α-SMA、CTGF、E-Cadherin、TGF-β1、Smad3、Akt的蛋白表达（P < 0.05）；150 μmol/L的PQ能提高TGF-β1和mTOR的mRNA表达，以及α-SMA、E-Cadherin、TGF-β1、Smad3的蛋白表达（P < 0.05）；450 μmol/L的PQ能提高CTGF和Smad3的mRNA表达，以及α-SMA、E-Cadherin、Smad3的蛋白表达（P < 0.05）。在不同浓度Que干预PQ（150 μmol/L）染毒的MLE-12细胞后，与阳性对照组相比，30 μmol/L的Que能降低α-SMA、TGF-β1、Akt、mTOR的mRNA和蛋白表达水平，以及α-SMA、CTGF、Akt、mTOR的蛋白表达水平（P < 0.05）；60 μmol/L的Que能提高CTGF、E-Cadherin、Smad3、Akt的mRNA表达水平，以及α-SMA、Smad3、mTOR的蛋白表达水平（P < 0.05）；90 μmol/L的Que能降低TGF-β1、mTOR的mRNA表达水平，提高CTGF的mRNA表达水平，降低Akt、mTOR的蛋白表达水平（P < 0.05）。
  结论  百草枯染毒可能通过TGF-β1诱导细胞发生上皮间质转化。槲皮素干预能提高百草枯染毒MLE-12细胞的存活率，并能改变细胞上皮间质转化程度，其机制可能是通过调控TGF-β1/Smad和Akt/mTOR信号通路实现。
     

桑椹提取物对β-淀粉样蛋白致PC12细胞损伤保护作用的初步研究

目的观察桑椹提取物(ME)对β-淀粉样蛋白(Aβ25-35)致PC12细胞损伤的保护作用,并初步探讨相关机制。方法将细胞分为对照组(未加任何处理因素)、Aβ25-35组(20μmol/L Aβ25-35损伤24h)以及(25、50、100、200、400和800μg/ml)ME预孵育组(ME预孵育24h后再给予20μmol/L Aβ25-35继续损伤24h),采用MTT法确定ME的干预浓度。在此基础上,将细胞分为对照组(未加任何处理因素)、ME组(200μg/ml ME作用24h)、Aβ25-35组(20μmol/L Aβ25-35损伤24h)以及ME预孵育+Aβ25-35组(200μg/ml ME预孵育24h后再给予20μmol/L Aβ25-35继续损伤24h),采用分子探针DCFH-DA及Hoechst33342染色法分别进行细胞内活性氧(ROS)含量及细胞凋亡的测定。结果 (1)与对照组相比,Aβ25-35组细胞存活率显著降低(P<0.05);与Aβ25-35组相比,100、200μg/ml ME预孵育组细胞存活率显著提高(P<0.05)。(2)与对照组相比,200μg/ml ME组细胞ROS的生成及细胞凋亡率无显著变化(P>0.05),而Aβ25-35组细胞内ROS的生成显著升高(P<0.05)、细胞凋亡率也明显增加(P<0.05);与Aβ25-35组相比,200μg/ml ME预孵育组细胞内ROS的生成显著减少(P<0.05)且细胞凋亡率明显降低(P<0.05)。结论桑椹提取物对Aβ25-35致PC12细胞损伤有明显的保护作用,机制与其抗氧化及抑制凋亡作用有关。     

辛伐他汀下调OX—LDL诱导的NRK52E细胞LOX-1表达和ROS生成

目的 探讨辛伐他汀对氧化低密度脂蛋白（ox-LDL）诱导的NRK52E细胞血凝素样氧化低密度脂蛋白受体（lectin-like ox-LDL receptor,LOX-1）表达和活性氧生成的作用.方法 体外培养NRK-52E,同步化后分为三组：（1）空白对照组（NRK52E细胞＋0μg/ml ox-LDL）;（2） ox-LDL组（NRK52E细胞＋50 μg/ml ox-LDL）;（3）辛伐他汀组（NRK52E细胞＋10μmol/L辛伐他汀＋50 μg/mlox-LDL）,用Western blot测定LOX-1蛋白表达,激光共聚焦检测ROS的表达.结果 （1）正常NRK52E细胞表达LOX-1非常低,50 μg/ml ox-LDL明显刺激NRK52E细胞表达LOX-1增加6.80倍,加用10 μmol/L辛伐他汀后,ox-LDL刺激的NRK52E细胞LOX-1表达降低65％;（2）正常NRK52E细胞内ROS生成很少,50 μg/ml ox-LDL可明显刺激NRK52E细胞内ROS生成增多了4.86倍,加用10μmol/L辛伐他汀后,ox-LDL刺激的NRK52E细胞ROS生成减少60％.结论 辛伐他汀可下调ox-LDL诱导的NRK52E细胞LOX-1表达和ROS生成,从而保护肾脏.     

Heavy Metal Contaminants in Tissues of the Garfish, <Emphasis Type="Italic">Belone belone</Emphasis> L., 1761, and the Bluefish, <Emphasis Type="Italic">Pomatomus saltatrix</Emphasis> L., 1766, from Turkey Waters

Levels of contaminants in fish are of particular interest because of the potential risk to humans who consume them. Fish samples were collected through the coastal waters of Turkey and the contents of cadmium, cobalt, chrome, copper, iron, manganese, nickel, zinc and lead in the liver and muscle tissues were determined. Among the metals analyzed, copper, zinc and iron were the most abundant in the different tissues while cadmium and lead were the least abundant both in Belone belone and Pomatomus saltatrix. Metal concentrations in muscles of fish species were found 0.01–0.38 mg kg⁻¹ for cadmium, 0.01–0.53 mg kg⁻¹ for cobalt, 0.05–1.87 mg kg⁻¹ for chromium, 0.21–5.89 mg kg⁻¹ for copper, 9.99–43.3 mg kg⁻¹ for iron, 0.14–1.33 mg kg⁻¹ for manganese, 0.06–4.70 mg kg⁻¹ for nickel, 0.09–0.81 mg kg⁻¹ for lead, 3.85–15.9 mg kg⁻¹ for zinc, respectively. Regional changes in metal concentration were observed in the tissues of both species, but these variations may not influence consumption advisories.     

Cognitive predictors of COVID-19 mitigation behaviors in vaccinated and unvaccinated general population members

BackgroundGiven the long-term threat posed by COVID-19, predictors of mitigation behaviors are critical to identify. Prior studies have found that cognitive factors are associated with some COVID-19 mitigation behaviors, but few studies employ representative samples and no prior studies have examined cognitive predictors of vaccination status. The purpose of the present study was to examine associations between cognitive variables (executive function, delay discounting, and future orientation) and COVID-19 mitigation behaviors (mask wearing, social distancing, hand hygiene and vaccination) in a population representative sample.MethodsA population representative sample of 2,002 adults completed validated measures of delay discounting, future orientation, and executive function. Participants also reported frequency of mitigation behaviors, vaccination status, and demographics.ResultsFuture orientation was associated with more mask wearing (β = 0.160, 95 % CI [0.090, 0.220], p < 0.001), social distancing (β = 0.150, 95 % CI [0.070, 0.240], p < 0.001), hand hygiene behaviors (β = 0.090, 95 % CI [0.000, 0.190], p = 0.054), and a higher likelihood of being fully vaccinated (OR = 0.80, 95 % CI [0.670, 0.970], p = 0.020). Lower delay discounting predicted more consistent mask wearing (β = −0.060, 95 % CI[−0.120, −0.010], p = 0.032) and being fully vaccinated (OR = 1.28, 95 % CI [1.13, 1.44], p < 0.001), while more symptoms of executive dysfunction predicted less mask wearing (β = −0.240, 95 % CI [−0.320, −0.150] p < 0.001) and hand hygiene (β = −0.220, 95 % CI [−0.320, −0.130], p < 0.001), but not vaccination status (OR = 0.96, 95 % CI [0.80, 1.16], p = 0.690) or social distancing behaviors (β = −0.080, 95 % CI [−0.180, 0.020], p = 0.097). Overall, social distancing was the least well-predicted outcome from cognitive factors, while mask wearing was most well-predicted. Vaccination status was not a significant moderator of these effects of cognitive predictors on mitigation behaviors.ConclusionsCognitive variables predict significant variability in mitigation behaviors. regardless of vaccination status. In particular, thinking about the future and discounting it less may encourage more consistent implementation of mitigating behaviors.     

Hypocalcaemia,alcohol drinking and viroimmune responses in ART recipients

Metabolic perturbations associated with HIV and antiretroviral therapies are widespread. Unfortunately, research has predominantly focused in cardiometabolic problems, neglecting other important areas. In fact, the immune-calcium–skeletal interface has been understudied despite its potential relevance in people living with HIV (PLWH). Using a case-control methodology, 200 PLWH receiving medical care were enrolled and stratified according to hazardous vs. non-hazardous alcohol intake (HAU vs. non-HAU) and calcium (Ca) levels by analyzing baseline data. The group was chosen to represent relatively "pure" HAU with minimal drug use and no psychiatric diagnoses. With these narrow parameters in place, we found evidence that HAU significantly increases TNF-α levels compared to Non-HAU (2.8 ± 0.6 vs. 1.9 ± 0.3 pg/ml, p = 0.05) and decreases blood Ca levels (9 ± 0.6 vs. 9.4 ± 0.5, p = 0.03). Our analyses also suggest that chronic inflammation, as indicated by increased TNF-α levels, is associated with hypocalcemia (hypoCa <8.6). Despite the limited prevalence of hypoCa, these findings are clinically significant given that hypoCA PLWH exhibited decreased CD4 (253 ± 224 vs. 417.7 ± 281, p = 0.02), B cells (147 ± 58 vs. 248 ± 151, p = 0.03) and NK cells (146.8 ± 90 vs. 229 ± 148, p = 0.008) and elevated CD8 (902.5 ± 438 vs. 699 ± 510, p = 0.09) compared to those with normal calcium. Furthermore, calcium effects on viral load were also evident with hypoCA exhibiting the highest loads (140,187 ± 111 vs. 35,622 ± 7770 HIV copies, p = 0.01). Multivariate analyses confirmed the significance of hypoCa in predicting viroimmune parameters. This paper provides the first evidence that hypoCa accounts for some of the variation in viroimmune measures in HAART recipients and suggests that hypoCa may be mediating alcohol's deleterious effects.     

Selection of Gut-Resistant Bacteria and Construction of Microbial Consortia for Improving Gluten Digestion under Simulated Gastrointestinal Conditions

This work aimed to define the microbial consortia that are able to digest gluten into non-toxic and non-immunogenic peptides in the human gastrointestinal tract. Methods: 131 out of 504 tested Bacillus and lactic acid bacteria, specifically Bacillus (64), lactobacilli (63), Pediococcus (1), and Weissella (3), showed strong gastrointestinal resistance and were selected for their PepN, PepI, PepX, PepO, and PepP activities toward synthetic substrates. Based on multivariate analysis, 24 strains were clearly distinct from the other tested strains based on having the highest enzymatic activities. As estimated by RP-HPLC and nano-ESI–MS/MS, 6 cytoplasmic extracts out of 24 selected strains showed the ability to hydrolyze immunogenic epitopes, specifically 57–68 of α9-gliadin, 62–75 of A-gliadin, 134–153 of γ-gliadin, and 57–89 (33-mer) of α2-gliadin. Live and lysed cells of selected strains were combined into different microbial consortia for hydrolyzing gluten under gastrointestinal conditions. Commercial proteolytic enzymes (Aspergillus oryzae E1, Aspergillus niger E2, Bacillus subtilis Veron HPP, and Veron PS proteases) were also added to each microbial consortium. Consortium activity was evaluated by ELISA tests, RP-HPLC-nano-ESI–MS/MS, and duodenal explants from celiac disease patients. Results: two microbial consortia (Consortium 4: Lactiplantibacillus (Lp.) plantarum DSM33363 and DSM33364, Lacticaseibacillus (Lc.) paracasei DSM33373, Bacillus subtilis DSM33298, and Bacillus pumilus DSM33301; and Consortium 16: Lp. plantarum DSM33363 and DSM33364, Lc. paracasei DSM33373, Limosilactobacillus reuteri DSM33374, Bacillus megaterium DSM33300, B. pumilus DSM33297 and DSM33355), containing commercial enzymes, were able to hydrolyze gluten to non-toxic and non-immunogenic peptides under gastrointestinal conditions. Conclusions: the results of this study provide evidence that selected microbial consortia could potentially improve the digestion of gluten in gluten-sensitive patients by hydrolyzing the immunogenic peptides during gastrointestinal digestion.     

Die Rolle des Bundes bei der Verhütung und Bekämpfung von Infektionskrankheiten

Zusammenfassung Die Gesundheitspolitik steht heute und auch in Zukunft vor der Herausforderung, das Gesundheitswesen qualitativ auf einem hohen Stand und gleichzeitig finanzierbar zu halten. Dazu bedarf es eines umfassenden Systems gesundheitlicher Sicherung, das allen Bürgern wirksam und ohne Hindernisse zur Verfügung steht. Wenngleich die Bürger in hohem Maß für die Förderung und den Erhalt ihrer Gesundheit selbst verantwortlich sind, ist es die Aufgabe des Staates, gegen Gefahren Vorsorge zu treffen, die von gefährlichen Krankheitserregern, Produkten oder auch von Umwelteinflüssen ausgehen können. Es gilt, den Schutz gegen bisher bekannte Gefahren auszubauen, neuen Bedrohungen entgegenzutreten und neue wissenschaftliche Erkenntnisse zu berücksichtigen. Prävention, Gesundheitsförderung und Gesundheitsschutz sind wichtige Schlüssel zur Verbesserung des Gesundheitszustands der Bevölkerung sowie zur Senkung der Kosten des Gesundheitssektors und stellen daher eine wichtige Säule im Gesundheitswesen dar. Die Prävention von Infektionskrankheiten und der Infektionsschutz bilden dabei prioritäre Aufgaben in der Fortentwicklung eines leistungsfähigen Gesundheitswesens in Deutschland. Die Bewältigung der genannten Aufgaben bei der Bekämpfung von Infektionskrankheiten erfordert das enge Zusammenwirken einer Reihe von Bundesoberbehörden und Bundesinstituten im Zuständigkeitsbereich des Ministeriums für Gesundheit und Soziale Sicherung sowie des Bundesministerium für Verbraucherschutz, Ernährung und Landwirtschaft.     

Factors Associated With Nurses' Job Satisfaction In Residential Long-term Care: The Importance of Organizational Context

ObjectivesWe examined demographic, individual, and organizational context factors associated with nurses' job satisfaction in residential long-term care (LTC) settings. Job satisfaction has implications for staff turnover, staff health, and quality of care.DesignA cross-sectional analysis of survey data collected in the Translating Research in Elder Care program.Setting and participantsN = 756 nurses (registered nurses: n = 308; licensed practical nurses: n = 448) from 89 residential LTC settings in 3 Western Canadian provinces.MethodsWe used a generalized estimating equation model to assess demographic, individual, and organizational context factors associated with job satisfaction. Job satisfaction was measured using the Michigan Organizational Assessment Questionnaire Job Satisfaction Scale.ResultsDemographic, individual, and organizational context factors were associated with job satisfaction among nurses in residential LTC settings. At the demographic level, hours worked in 2 weeks (B = 0.002, P = .043) was associated with job satisfaction. At the individual level, emotional exhaustion-burnout (B = −0.063, P = .02) was associated with lower job satisfaction, while higher scores on empowerment (meaning) (B = 0.140, P = .015), work engagement (vigor) (B = 0.096, P = .01), and work engagement (dedication) (B = 0.129, P = .001) were associated with higher job satisfaction. With respect to organizational context, culture (B = 0.175, P < .001), organizational slack-space (eg, perceived availability and use of adequate space; B = 0.043, P = .040), and adequate orientation (B = 0.092, P < .001) were associated with higher job satisfaction.Conclusions and implicationsWe identified previously unexamined modifiable organizational features (organizational slack-space and adequate orientation) as factors associated with LTC nurses' job satisfaction in the Canadian context. Our findings support future efforts to improve job satisfaction through improvements in organizational space and provision of adequate workplace orientation.     

Title: Differentiating the effects of whey protein and guar gum preloads on postprandial glycemia in type 2 diabetes

Background and aimsWhey protein and guar gum have both been reported to reduce postprandial glycemia in health and type 2 diabetes, associated with stimulation of glucagon-like peptide-1 (GLP-1) and/or slowing of gastric emptying. Our aim was to evaluate, in type 2 diabetes, the acute effects of low dose “preloads” of whey and guar, given alone or in combination before a meal, on postprandial glycemia, insulin, GLP-1, and gastric emptying.Methods21 patients with type 2 diabetes, managed by diet or metformin alone, were each studied on 4 days. They received a preload “shake” 15min before a mashed potato meal (368.5 kcal) labeled with ¹³C-octanoic-acid. The preloads comprised either (i) 17 g whey (W), (ii) 5 g guar (G), (iii) 17 g whey + 5 g guar (WG) each sweetened with 60 mg sucralose, and (iv) 60 mg sucralose alone (control; C), all dissolved in 150 mL water. Venous blood was sampled frequently for measurements of glucose, insulin, and GLP-1 concentrations. Gastric half-emptying time (T50) was calculated from breath ¹³CO₂ excretion over 240 min.ResultsPostprandial blood glucose concentrations were lower with W and WG compared to C (each P < 0.0001, treatment × time interaction), and lower after G than C only at 30min. Insulin, GLP-1, and glucagon concentrations were higher after W than WG, G, or C (P < 0.05, treatment × time interaction), without differences between the latter three. Gastric emptying was slower with W (T50: 179.6 ± 6.1 min, P < 0.05) and WG (T50: 197.6 ± 9.7 min, P < 0.0001) when compared to C (T50: 162.9 ± 6.2 min), but did not differ between G (T50: 171.3 ± 7.0) and C (P > 0.99).ConclusionBoth whey and whey/guar preloads reduced postprandial glycemia, associated with slowing of gastric emptying. Low dose guar was less effective as a preload for glucose-lowering and did not slow gastric emptying.Clinical Trial Registry number and websiteAustralian and New Zealand Clinical Trials Registry, Trial ID ACTRN12615001272583, http://www.anzctr.org.au     

Measurements and Characteristics of Nitrogen-Containing Compounds in Atmospheric Particulate Matter in Beijing, China

The total nitrogen (TN) and water-soluble nitrogenous ions were determined by using CHN Elemental Analyzer and ion chromatography method, respectively, from November 24, 1998 to February 12, 1999 in Beijing. The average concentrations of TN, NH₄ ⁺ and NO₃ ⁻ were 10.62 μg N m⁻³, 6.67 μg m⁻³ and 10.01 μg m⁻³, respectively. The total inorganic nitrogen (IN) calculated from NH₄ ⁺ and NO₃ ⁻ was 7.45 μg N m⁻³, accounting for 70% of TN, i.e., 30% of TN existed as organic nitrogen form (ON). The correlation between ON and other pollution tracers showed that, coal combustion, biomass burning, soil humic matter and secondary formation were the important sources of ON in particulate matter in Beijing.     

Neutralizing antibody activity,safety and immunogenicity of human anti-rabies virus monoclonal antibody (Ormutivimab) in Chinese healthy adults: A phase Ⅱb randomized,double-blind,parallel-controlled study

ObjectiveThis study was a randomized, double-blind, parallel-controlled trail to evaluate the rabies virus neutralizing activity（RVNA）, safety and immunogenicity of Ormutivimab + rabies vaccine in Chinese healthy adults.MethodsSubjects were randomly and equally assigned to 4 groups (20 IU/kg Omtv + vaccine, 40 IU/kg Omtv + vaccine, 20 IU/kg HRIG + vaccine, and placebo + vaccine). Subjects received vaccine as the WHO Essen regime combined with Omutivimab、HRIG or placebo on Day 0. The study lasted for 43 days.ResultsA total of 240 subjects were simultaneously assigned to both FAS and SS. Fifty subjects with baseline RVNA > 0.05 IU/ml (detection limit) were excluded, 190 were included into mITT.All the subjects from 40 IU/kg Omtv + vaccine group had a protection level of RNVA (≥0.5 IU/ml, WHO) on Day 14, and those in 20 IU/kg Omtv + vaccine group and placebo + vaccine group converted positive 100 % on Day 28. In contrast to 20 IU/kg HRIG + vaccine and placebo + vaccine, Ormutivimab + vaccine provided a higher RVNA during Days 0 to 7. And RVNA in 40 IU/kg Omtv + vaccine and 20 IU/kg Omtv + vaccine groups were always higher than 20 IU/kg HRIG + vaccine group during the whole study. Although anti-Omtv antibody were detected in some subjects, it did not influence the RVNA. The incidence of adverse reactions was significantly lower in 20 IU/kg Omtv + vaccine group (17.2 %) than in 40 IU/kg Omtv + vaccine (36.7 %) and 20 IU/kg HRIG + vaccine groups (40.3 %).ConclusionCompared with HRIG + vaccine and placebo + vaccine, Omtv + vaccine provided higher RNVA for earlier immune protection. The interference of Ormutivimab on the long-term immune protection induced by rabies vaccine is weaker than HRIG. At the same dose, the adverse reactions of Omtv + vaccine group were less than HRIG + vaccine group.Registration: ClinicalTrials.gov #NCT02559921.