Cytokine production by co-cultures exposed to monodisperse amorphous silica nanoparticles: the role of size and surface area

The aim of this study was to test the influence of nanoparticle size and surface area (SA) on cytokine secretion by co-cultures of pulmonary epithelial cells (A549), macrophages (differentiated THP-1 cells) and endothelium cells (EA.hy926) in a two-compartment system. We used monodisperse amorphous silica nanoparticles (2, 16, 60 and 104 nm) at concentrations of 5 μg/cm2 cell culture SA or 10 cm2 particle SA/cm2. A549 and THP-1 cells were exposed to nanoparticles for 24h, in the presence of EA.hy926 cells cultured in an insert introduced above the bi-culture after 12h. Supernatants from both compartments were recovered and TNF-α, IL-6, IL-8 and MIP-1α were measured. Significant secretion of all cytokines was observed for the 2 nm particles at both concentrations and in both compartments. Larger particles of 60 nm induced significant cytokine secretion at the dose of 10 cm2 particle SA/cm2. The use of multiple cellular types showed that cytokine secretion in single cell cultures is amplified or mitigated in co-cultures. The release of pro-inflammatory mediators by endothelial cells not directly exposed to nanoparticles indicates a possible endothelium activation after inhalation of silica particles. This work shows the role of size and SA in cellular response to amorphous nanosilica.     

缺氧缺血性脑病预后与脐动脉血乳酸水平等关系研究

目的探讨脐动脉血乳酸水平、阿氏评分、新生儿行为神经评分(NBNA)对新生儿缺氧缺血性脑病(HIE)预后判断的价值及临床意义。方法自2003年6月在我院产科出生的窒息新生儿,娩出后在第一声啼哭前立即抽取脐动脉血2ml送检乳酸,其中64例发生HIE的患儿按病情分为轻、中、重3组,第3天及第7天进行NBNA评分,随访至4岁行C-WYCSI智力测验,统计学方法分析上述临床资料。另选同期出生的80例正常新生儿为脐动脉血乳酸值正常对照组。结果各HIE组脐动脉血乳酸值较正常新生儿组均明显升高,脐动脉血乳酸值、阿氏评分、NBNA评分与C-WYCSI测验结果及四者之间均呈直线相关关系。结论脐动脉血乳酸水平能早期预测HIE的严重程度及预后,结合阿氏评分、HIE分度、NBNA评分动态观察结果,更有助于判定HIE患儿的预后。     

脓毒症休克心肌顿抑严重程度判断的临床研究

目的探讨脑钠肽（BNP）、心肌钙蛋白I（cTnI）、血乳酸及急性生理及慢性健康状况评分Ⅱ（APACHEⅡ评分）在脓毒症休克心肌顿抑严重程度判断中的应用价值。方法3l例确诊脓毒症休克患者,入院后1h内抽血查BNP、cTnI、血乳酸,并进行APACHElI评分,以后分别在开始治疗后6、24h监测上述指标。观察患者的最终预后,比较存活组和死亡组上述指标入院时的差异;分别比较不同预后组内各时间点上述指标的差异。结果3l例患者,死亡13例,存活18例,死亡率为41．9％。死亡组人院时各项指标数值均明显高于存活组[BNP：（3401．1±1710．2）pg／Lvs（1947．2±1319．5）pg／L,P=0．008;cTnI：（9．4±4．7）ng]L vs（5．1±4．4）．g／L,P=0．012;血乳酸：（10．8±4．9）mm01]L vs（7．1±4．5）mmol／L,P=0．027;APACHElI评分：29．4±5．7口s22．1-＋8．8,P：0．006]。死亡组患者中,治疗6h上述指标与入院时比较差异无统计学意义（P均〉0．05）,治疗后24hBNP[（4757．9-＋2044．4）pg／L vs（3401．1-＋1710．2）og／L,P=0．0111、血乳酸【（12．4-＋3．2）mmol／LVS（8．8±4．9）mmol／L,P=0．0311、APACHEII评分（34．6±6．1ws29．4±5．7,P=0．029）均明显高于人院时（P均〈0．05）,eTnI差异无统计学意义（P〉0．05）。存活组患者中．治疗6h[BNP：（1125．2＋563．3）pg／L vs（1947．2±l319．5）pgCL;eTnI：（2．1±1．4）ng／L vs（5．1＋4．4）nv4L;血孚L酸：（4．4±2．7）mmol／LVS（7．1±4．5）mmol／L;A．PACHEII评分：15．5±7．9vs22．1±8．81、24h]BNP：（578．1±345．5）pg／L vs（1947．2±l319．5）pz-／L;eTnI：（0．9±0．5）ng／L vs（5．1±4．4）ng／L;血乳酸：（2-4±1．3）mmol／Lvs（7．1±4．5）mmol／L;APACHEⅡ评分：10．4±2．8vs22．1±8．81各项指标均较入院时明显降低,差异有统计学意义（P均〈0．05）。结论BNP、eTnI、血乳酸和APACHEll评分可反映脓毒症休克患者心肌顿抑的严重程度,预测患者预后．进一步可据此建立相关的脓毒症休克患者心肌顿抑严重程度评估系统。     

Spinal cord histopathology of MOG peptide 35-55-induced experimental autoimmune encephalomyelitis is time- and score-dependent

The neuroprotective effects of Jatrorrhizine from Coptidis Rhizoma against hydrogen peroxide (H(2)O(2))-induced rat pheochromocytoma line PC12 injury and its potential mechanisms were evaluated in the present study. When cells were exposed to H(2)O(2) (200 μM) for 12h, there was a significant reduction in cell survival and activity of antioxidant enzyme (SOD and HO-1) and LDH release. In addition, increased ROS production, declined MMP and increased production of malondialdehyde (MDA) were observed. Preincubation of cells with Jatrorrhizine (0.01-10.0 μM) 24h prior to H(2)O(2) exposure markedly elevated cell viability and activities of antioxidant enzyme (SOD and HO-1), prevented LDH release and lipid peroxidation (MDA) production, attenuated the decrease of MMP and scavenged ROS formation. Jatrorrhizine also attenuated caspase-3 activation of the downstream cascade following ROS. Our results suggest that Jatrorrhizine holds potential for neuroprotective effects against H(2)O(2)-induced injury.     

Preoperative predictors of mortality in adult patients with perforation peritonitis

Introduction:

There is paucity of data from India regarding the etiology, prognostic indicators, morbidity, and mortality patterns of perforation peritonitis. The objective of our study was to evaluate the predictors of mortality, preoperatively, for risk stratification of the patients and institution of an early goal-directed therapy.

Materials and Methods:

Eighty-four consecutive patients presenting with perforation peritonitis, in the age group of 14–70 years scheduled for emergency laparotomy were studied prospectively. The parameters studied were age and sex of the patients, associated co-morbidities, duration of symptoms, delay in initiating surgical intervention, and preoperative biochemical parameters such as hemoglobin, random blood sugar, blood urea, serum creatinine, pH, base excess, and serum lactate levels. In-hospital mortality was taken as the outcome.

Results:

We encountered a mortality of 17.8% in our study. Multiple linear (enter) regression identified the age, duration of symptoms, preoperative blood sugar levels, blood urea, serum creatinine levels, Mannheim Peritonitis Index, and the delay in instituting surgical intervention as independent predictors of mortality. Hyperlactatemia, acidosis and base excess were not found to be associated with mortality.

Conclusion:

Routine biochemical investigations, delay in presentation, and surgical intervention are good predictors of mortality. Recognizing such patients early may help the anesthesiologists in risk stratification and in providing an early goal-directed therapy.     

Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited (1)H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.     

13C high-resolution-magic angle spinning MRS reveals differences in glucose metabolism between two breast cancer xenograft models with different gene expression patterns

Tumor cells have increased glycolytic activity, and glucose is mainly used to form lactate and alanine, even when high concentrations of oxygen are present (Warburg effect). The purpose of the present study was to investigate glucose metabolism in two xenograft models representing basal-like and luminal-like breast cancer using (13) C high-resolution-magic angle spinning (HR-MAS) MRS and gene expression analysis. Tumor tissue was collected from two groups for each model: untreated mice (n=19) and a group of mice (n=16) that received an injection of [1-(13) C]-glucose 10 or 15 min before harvesting the tissue. (13) C HR-MAS MRS was performed on the tumor samples and differences in the glucose/alanine (Glc/Ala), glucose/lactate (Glc/Lac) and alanine/lactate (Ala/Lac) ratios between the models were studied. The expression of glycolytic genes was studied using tumor tissue from the same models. In the natural abundance MR spectra, a significantly lower Glc/Ala and Glc/Lac ratio (p<0.001) was observed in the luminal-like model compared with the basal-like model. In the labeled samples, the predominant glucose metabolites were lactate and alanine. Significantly lower Glc/Ala and Glc/Lac ratios were observed in the luminal-like model (p<0.05). Most genes contributing to glycolysis were expressed at higher levels in the luminal-like model (fdr<0.001). The lower Glc/Ala and Glc/Lac ratios and higher glycolytic gene expression observed in the luminal-like model indicates that the transformation of glucose to lactate and alanine occurred faster in this model than in the basal-like model, which has a growth rate several times faster than that of the luminal-like model. The results from the present study suggest that the tumor growth rate is not necessarily a determinant of glycolytic activity.     

肠癌根治术病人两种容量治疗方案效果的比较

目的 比较肠癌根治术病人麻醉诱导前6%羟乙基淀粉130/0.4.麻醉诱导后乳酸钠林格氏液血液稀释与麻醉诱导前乳酸钠林格氏液-麻醉诱导后6%羟乙基淀粉130/0.4血液稀释容量治疗的效果.方法 拟行肠癌根治术病人40例,ASA Ⅰ或Ⅱ级,年龄45～64岁,体重42～65 kg,随机分为2组(n=20),Ⅰ组麻醉诱导前经30min静脉输注6%羟乙基淀粉130/0.4 15 ml/kg,麻醉诱导后即刻经30 min静脉输注乳酸钠林格氏液15 ml/kg;Ⅱ组于麻醉诱导前经30 min静脉输注乳酸钠林格氏液15 ml/kg,麻醉诱导后即刻经30 min静脉输注6%羟乙基淀粉130/0.4 15 ml/kg.记录术中胶体液量、晶体液量、出血量、尿量和异体输血情况;于人室后(基础状态,T0)、麻醉诱导后即刻(T1、15 min(T2)、60 min(T3)、120 min(T4)及术毕(T5)时记录平均动脉压(MAP)、中心静脉压(CVP)和心率(HR);于T0、T1、T3、T5时抽取桡动脉血样1 ml行血气分析,并测定血红蛋白浓度(Hb)和红细胞压积(Hct).结果 两组均未输异体血,术中胶体液用量,晶体液用量、出血量、尿量差异无统计学意义(P>0.05);与基础值比较,Ⅰ组术中MAP、HCO-3、血浆乳酸、Na+、K+的浓度差异无统计学意义(P>0.05),CVP升高,HR、Hct、Hb降低,术毕时pH值降低,Ⅱ组术中CVP升高,MAP、HR、pH值降低,术毕时HCO-3降低(P<0.05),血浆乳酸、Na+、K+的浓度差异无统计学意义(P>0.05);与Ⅰ组比较,Ⅱ组术中CVP升高,术毕时血浆乳酸浓度降低(P<0.05).结论 肠癌根治术病人采用麻醉诱导前6%羟乙基淀粉130/0.4-麻醉诱导后乳酸钠林格氏液血液稀释的容量治疗效果较好.     

非水溶剂紫外分光光度法测定乳酸依沙吖啶溶液的含量

目的建立测定乳酸依沙吖啶溶液中乳酸依沙吖啶含量的非水溶剂紫外分光光度法。方法以无水乙醇作为稀释剂,在374nm处测定吸收度。结果乳酸依沙吖啶在2．5～20pg·mL^-1范围内具有良好的线性关系,R^2=0．9999,平均回收率为99．2％,RSD为0．92％。结论该法简便、快速、准确,可用于乳酸依沙吖啶溶液的含量测定。