Analysis of protein S-100B in serum: a methodological study.

BACKGROUND: Dysfunction and damage of the human central nervous system can be detected with biochemical markers, and protein S-100B is the best-established such marker. The aim of this study was to evaluate whether the protein is stable during long-term storage, to establish reference values for the new Elecsys S100 test and to compare this new method with the Liaison Sangtec 100 test. METHODS: We analysed blood samples from 118 blood donors and 196 patients with subarachnoid haemorrhage or head injury. The long-term stability of S-100B in frozen serum samples was evaluated with repeated analysis in 1997 and 2003 using an immunoradiometric assay. Method comparison between the Liaison Sangtec 100 and Elecsys S100 tests was performed using Bland-Altman difference plots. RESULTS: Serum concentrations increased significantly during long-term storage (mean difference 0.15 microg/L; +/-2 SD, 0.55 microg/L). Serum measurements using the Elecsys S100 method in 118 healthy blood donors showed S-100B levels between 0.02 and 0.08 microg/L (mean 0.05). The 95th percentile was 0.07 microg/L. The Liaison Sangtec 100 test usually measured higher concentrations than the Elecsys S100 method, and the difference between the two methods increased with increasing concentrations. The mean difference between the methods was 0.14 microg/L (+/-2 SD, 0.39 microg/L). CONCLUSIONS: Protein S-100B is not stable during long-term storage and the two analytical methods are not interchangeable.     

重型颅脑损伤患者血浆S-100B蛋白测定的临床意义

目的　探讨血浆 S 10 0 B蛋白作为一种生物学指标在重型颅脑损伤诊断及预后判断中的应用价值。方法　重型颅脑损伤患者 6 6例 ,伤后早期 (2～ 6 h)抽取血浆标本 ,并从伤后 2 4 h起连续 3～ 7d检测血浆 S 10 0 B蛋白含量 ,将其结果与患者伤后 6个月格拉斯哥预后评分 (GOS)进行比较。结果　 6 6例患者中死亡 2 5例 ,致残 2 2例 ,良好 19例。死亡组 S 10 0 B平均 2 .6 0 μg/ L,明显高于存活组 (0 .5 5 μg/ L,P<0 .0 0 1) ;死亡组中有 14例 S 10 0 B峰值超过 2 .0 0 μg/ L,而存活组中只有 4例峰值超过 2 .0 0 μg/ L(P<0 .0 0 5 )。结论　血浆 S 10 0 B蛋白在重型颅脑损伤的诊断及预后判断中具有可靠的应用价值。     

局部亚低温条件下脑梗死病人血清S-100b蛋白的变化

目的探讨局部亚低温治疗对脑梗死病人血清S-100b蛋白的影响。方法将52例急性脑梗死患者按1：1配对分为亚低温治疗组（26例）和常规治疗组（26例），EHSA法检测血清S-100b蛋白含量。同时检测26例正常人（对照组）血清S-100b蛋白含量。结果脑梗死病人血清S-100b蛋白含量明显高于对照组（P〈0．01）；亚低温治疗组病人血清S-100b蛋白含量明显低于非亚低温治疗组，有显著差异（P〈0．05）。结论1急性脑梗死病人血清S-100b蛋白水平明显高于正常人，因此S-100b蛋白可作为脑梗死病情观察指标。2局部亚低温治疗能降低脑梗死病人血清S-100b蛋白水平，提示局部亚低温能发挥脑保护作用。     

Impairment of blood-brain barrier integrity during carotid surgery as assessed by serum S-100B protein concentrations.

During carotid endarterectomy (CEA) the internal carotid artery is cross-clamped for a period of several minutes. This maneuver may cause cerebral hypoperfusion and/or impairment of the blood-brain barrier (BBB) even in cases where clinical signs are absent. The aim of the present study was to examine whether such alterations could be detected by monitoring the cerebral marker S-100B protein concentrations during and after CEA in the serum. Twenty-five consecutive patients (17 M/8 F, mean age: 64.2 years, range 47-79 years) undergoing elective CEA at our department were studied. All of these patients were without perioperative neurological deficit. Intraoperative samples were collected from internal jugular and peripheral venous blood: 1) before carotid cross-clamping; 2) immediately before declamping; 3) after clamp release. Postoperative samples were taken from peripheral blood at 6 and 24 h, respectively. S-100B was assayed in sera using an immunoluminometric technique. During carotid cross-clamping, S-100B protein concentrations in the ipsilateral jugular serum significantly (p < 0.02) increased to pre-clamp values. After declamping, however, S-100B returned to the baseline level. No differences were seen between the responses of hypertensive and normotensive patients. There was no correlation between carotid occlusion time and S-100B protein concentrations. In the peripheral venous serum no significant changes in S-100B concentrations were detected during or after CEA. We presume that the elevation of S-100B protein concentration during CEA in patients with no neurological deficits indicates the transient opening of the BBB elicited by carotid cross-clamping.     

Protein S-100B: a serum marker for ischemic and infectious injury of cerebral tissue.

The S-100B protein is released by injured astrocytes. After passage through a disintegrated blood-brain barrier (BBB) the molecule can be detected in the peripheral circulation. We investigated the association between the extent of brain injury and S-100B concentration in serum in cerebral injury caused by cerebral ischemia and cerebral fungal infection. Study I: The S-100B serum concentration was serially determined in 24 patients with ischemic stroke at 4, 8, 10, 24, 72 hours after the onset of symptoms. We observed that patients with brain lesions larger than 5 cm3 exhibited significantly increased serum levels of S-100B at 10, 24 and 72 hours compared to those with lesion volumes below 5 cm3. Furthermore, an association between S-100B serum concentration and neurological outcome was observed. Study II: In a mouse model of systemic fungal infection with Candida albicans we observed that serum levels of S-100B increased at day 1 after intravenous infection. At this time we could histologically demonstrate brain tissue injury by invading hyphae which had crossed the BBB. Furthermore, reactive astrogliosis was demonstrated by immunohistochemistry. On day 7 we found a significant decrease of S-100B serum level compared to day 1 and 4. This was associated with a demarcation of the fungi with leukocytes in brain tissue at this late phase of infection. No further invasion through the BBB was seen on day 7. In conclusion, serum levels of S-100B reflect the time course of tissue injury in cerebral ischemia and cerebral infection to a similar extent. Thus, S-100B may be a useful marker to assess cerebral tissue injury.     

Serum levels of neural protein S-100B in phenylketonuria

BACKGROUND: Serum neural protein S-100B concentration is considered as a marker of CNS lesions. Phenylketonuria (PKU) is a metabolic disorder characterized by high phenylalanine (Phe) levels in blood and foci of myelin absence in the CNS of untreated patients. AIM: To evaluate S-100B blood levels in PKU patients. METHODS: Twenty-five (N = 25) PKU patients of comparable age, who were diagnosed by neonatal screening and "followed up" in our Inborn Error of Metabolism Department, were divided into two groups: group A (N = 13) with almost normal Phe levels and group B (N = 12) "off diet" with high Phe concentrations. Their MRI examinations were normal 12-14 months before the beginning of the study. Twenty-three (N = 23) healthy children were the controls. Serum S-100B levels, measured with an immunoluminometric assay, were greatly elevated in the group B (0.48 +/- 0.6 microg/l) as compared to those of group A (0.16 +/- 0.4 microg/l, P < 0.001) and controls (0.10 +/- 0.02, P < 0.001). Positive correlation was found between S-100B and Phe blood concentration (r = 0.46, P < 0.01). Foci of myelin absence in MRIs were observed in 1/13 of group A and in 10/12 of group B at the end of this study. CONCLUSIONS: (a) Serum S-100B protein level, for the first time evaluated in PKU, was positively correlated with Phe blood level in PKU patients. (b) S-100B blood estimation could be a useful peripheral marker of CNS lesions in patients with demyelinated disease such as PKU.     

Comparison of three assays for quantifying S-100B in serum

BackgroundSerum S-100B has clinical value in monitoring malignant melanoma and in monitoring and predicting outcomes in patients with traumatic brain injury.MethodsAnalytical performance characteristic and split-sample method comparison studies for three commercial S-100B immunoassays (CanAg® S100, Sangtec® 100, YK150 Human S-100 β) were performed. Reference intervals (97.5th percentile) for each assay were established by non-parametric analysis of results from healthy volunteers.ResultsLinearity results were slope = 1.014, intercept = 65.1, r² = 0.999 for the Sangtec assay; slope = 1.038, intercept = 31.1, r² = 0.999 for the CanAg assay; slope = 1.123, intercept = ? 105.4, r² = 0.997 for the YK150 assay. Within-run CVs were ≤ 5.7, ≤ 6.3 and ≤ 10.8 for the Sangtec, CanAg and YK150 ELISAs, respectively. Between-run CVs were ≤ 11.3, ≤ 5.9 and ≤ 9.5, respectively. Upper reference interval limits of 141, 96 and 735 ng/l S-100B were established for the Sangtec, CanAg and YK150 ELISAs, respectively. Deming regression generated the following: CanAg vs. Sangtec, slope = 0.339, intercept = 24.1, r² = 0.932; YK150 vs. Sangtec, slope = 0.266, intercept = ? 140.0, r² = 0.690; YK150 vs. CanAg, slope = 1.376, intercept = ? 13.1, r² = 0.860.ConclusionsThe configurations, procedures and performance characteristics of the Sangtec and CanAg S-100B ELISAs are comparable and better than those of the YK150 assay. Poor agreement and large biases prevent interchangeable use of results.     

Stability of ketone bodies in serum in dependence on storage time and storage temperature

The serum concentrations of beta-hydroxybutyrate and acetoacetate as well as the beta-hydroxybutyrate/acetoacetate ratio are important parameters for the differential diagnosis of certain inborn errors of metabolism. Acetoacetate, however, is an unstable compound which becomes rapidly decarboxylated. At a storage temperature of -20 degrees C about 40% of the acetoacetate is lost within 7 days and after 40 days storage at this temperature virtually all of the acetoacetate has become degraded. At -80 degrees C the decomposition of acetoacetate occurs with a much slower rate and only 15% of the initial acetoacetate is lost after 40 days storage. The rate constants for the decarboxylation reaction were found to be (6.4 +/- 2.9) * 10(-5) [min(-1)] at -20 degrees C and (0.4 +/- 0.3) * 10(-5) [min(-1)] at -80 degrees C. In contrast, beta-hydroxybutyrate is very stable during storage and hence should be used as main parameter for the evaluation of ketonemia. If determination of acetoacetate and/or of the beta-hydroxybutyrate/acetoacetate ratio is necessary, an assay immediately after collecting the serum samples is recommended. Otherwise, the serum samples should be frozen as soon as possible and stored at -80 degrees C during transport and storage.     

乌司他丁对大鼠心肺复苏后早期血清S-100B蛋白和NSE的影响

目的 探讨乌司他丁(UTI)对大鼠心肺复苏(CPR)后早期血清S-100B蛋白、神经元特异性烯醇化酶(NSE)及海马病理改变的影响及作用.方法 成年雄性SD大鼠随机分为假手术对照组、复苏组和UTI组,每组10只.采用窒息法致复苏组和UTI组大鼠心脏骤停(CA),继而进行心肺复苏(CPR).UTI组于自主循环恢复(ROSC)后2 min内经颈动脉推注注射用UTI 100 000 U/kg,与生理盐水配伍成2 mL溶液.对照组仅行麻醉、气管切开和血管穿刺.复苏组和UTI组于ROSC后1 h,对照组于气管切开后1 h经颈动脉取血和快速断头取左侧脑海马组织.采用双抗体夹心酶联免疫吸附法(ELISA)分别检测血清S-100B蛋白与NSE水平;光镜下观察海马的病理改变.结果 与假手术对照组比较,复苏组和UTI组大鼠血清S-100B蛋白与NSE浓度在ROSC后1 h均明显升高(P<0.01);与复苏组比较,UTI组大鼠血清S-100B蛋白浓度显著降低(P<0.01),而NSE的浓度降低不明显(P>0.05).UTI组病理损害轻于复苏组.结论 UTI能降低大鼠CPR后早期(1 h)血清S-100B蛋白和NSE水平,减轻病理损伤,对CPR过程中的脑组织具有保护作用.     

标本存放温度和时间对血浆中抗凝蛋白活性的影响

目的探讨标本存放温度和时间对血浆中抗凝蛋白活性的影响。方法用真空采血管采集住院患者空腹静脉血20例,无黄疸、脂血、溶血,即刻以3 000r/min离心10min,上机测得的结果与在室温(20~25℃)、4℃和-20℃放置4h、12h、24h、7d、14d的血浆标本测得的结果分别进行比较。结果在室温下保存ATⅢ、PC活性24h内均无明显变化,仅PS活性明显降低,7d和14d时检测抗凝蛋白活性均明显降低(P0.05);在4℃放置7dATⅢ、PC活性有所降低,但与即时活性相比差异无统计学意义,而PS活性明显下降(P0.05),14d时三者活性均明显下降(P0.05);在-20℃保存14d甚至更长时间抗凝蛋白活性均无明显降低。结论为保证抗凝蛋白活性,血液标本应置于低温保存并尽快检测。     

热性惊厥患儿血清S-100蛋白及髓鞘碱性蛋白的变化

目的:检测热性惊厥(FS)患儿血清S-100蛋白、髓鞘碱性蛋白(MBP)水平的变化,寻找反映FS惠儿脑损伤的生化指标.方法:诊断为上呼吸道感染并FS患儿63例为病例组,其中单纯性热性惊厥(SFS)组45例,复杂性热性惊厥(CFS)组18例.选择20例健康儿童为对照组.采用ELSA法作血清S-00β和MBP蛋白定量测定.结果:FS组血清S-100β含量显著高于对照组,差异有显著性意义(P＜0.05),但两组血清中MBP含量差异无显著性意义(P＞0.05).CFS组血清MBP含量显著高于SFS组,差异有显著性意义(P＜0.05).结论:FS组血清中S-100β显著高于对照组.提示FS发作时可能存在神经元损害.CFS组较SFS组MBP升高更为显著,表明CFS患儿中枢神经系统髓鞘损伤更明显.     

急性脑卒中患者血清S-100B蛋白的检测

目的 讨论急性脑卒中患者血清S-100B蛋白的表达规律及临床意义.方法 用ELISA法对70例急性脑卒中患者发病24 h内的血清S-100B蛋白含量及健康对照组40例进行检测.结果 急性脑卒中缺血性和出血性患者血清S-100B蛋白含量均显著高于健康对照组(P＜0.01);急性脑卒中缺血性和出血性患者血清S-100B蛋白含量比较,差异无统计学意义(P＞0.05);脑卒中含量高低与病情严重程度有密切关系.结论 血清S-100B蛋白的含量可作为急性脑卒中病情监测的指标.     

血清S-100β蛋白检测在肺性脑病中的意义

目的:检测血清S-100β蛋白在肺性脑病患者中的浓度,探讨其临床意义。方法:15例健康者为正常对照组,32例COPD无呼吸衰竭者,14例并发呼吸衰竭无肺性脑病者为病例对照组,22例肺性脑病患者为病例组,肺性脑病组分为轻型(9例)、中型(7)、重型(6例)3组。用双抗体夹心ELISA法检测血清中S-100β蛋白值,并进行比较分析。结果:血清中S-100β蛋白平均值:肺性脑病组(15.79±7.56μg/L)和COPD并发呼吸衰竭无肺性脑病组(11.20±4.68μg/L)显著高于COPD不并发呼吸衰竭组(7.45±4.40μg/L)和正常对照组(5.46±3.22μg/L)(P0.05)。肺性脑病中,中型(18.18±5.19μg/L)和重型(21.64±9.56μg/L)显著高于轻型(10.03±2.15μg/L)(P0.05),重型和中型无统计学意义(P0.05)。结论:检测血清S-100β蛋白有助于了解有否发生脑损害并且有助于反应脑损害的程度。     

血清S-100B蛋白联合NSE水平对新生儿缺氧缺血性脑病的预后评估价值

目的探讨血清S-100B蛋白联合神经元特异性烯醇化酶(NSE)水平对新生儿缺氧缺血性脑病(HIE)的预后评估价值。方法选取该院收治的HIE患儿118例,根据其预后情况分为存活组(n=88)和死亡组(n=30)。采用神经症状临床分度分为轻中度组(n=82)和重度组(n=36),比较各组第1、3、5天血清S-100B蛋白及NSE水平变化。应用受试者工作特征曲线(ROC曲线)分析血清S-100B蛋白及NSE水平预测HIE患儿死亡的价值。结果死亡组第1、3、5天血清S-100B蛋白及NSE水平均明显高于存活组,且死亡组血清S-100B蛋白及NSE水平呈升高趋势(P<0.05)。重度组第1、3、5天血清S-100B蛋白及NSE水平均明显高于轻中度组,且重度组血清S-100B蛋白及NSE水平呈升高趋势(P<0.05)。ROC曲线显示,第3天血清S-100B蛋白联合NSE水平预测HIE患儿死亡的ROC曲线下面积最大为0.950(95%CI 0.892~0.997),其灵敏度和特异度分别为95.2%和89.6%。相关分析显示,死亡组血清S-100B蛋白与NSE水平呈正相关(r=0.817,P<0.01)。结论血清S-100B蛋白与NSE水平与HIE患儿的病情严重程度相关,第3天两项指标联合预测HIE患儿预后的价值较高。     

Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy

OBJECTIVES: This study was designed to apply the rapid Elecsys S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys S100 immunoassay and compared to those obtained by the well-established LIA-mat S100 system. RESULTS: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys S100 system. CONCLUSIONS: The Elecsys S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.     

The significance of protein S-100B testing in cardiac arrest patients

Cardiac arrest often represents the first expression of an underlying cardiac disease. Despite advances in neurocritical care, the neurological assessment of cardiac arrest patients relies on clinical, instrumental and biochemical parameters. The clinical significance of S-100 calcium binding protein B (S-100B) has substantially increased throughout several areas of clinical neuroscience, but reliable evidences attest it can be used as a reliable and early predictor of poor physiological and cognitive neurological outcomes after cardiac arrest.