S100beta Levels Research Articles

The Accuracy of the S100B Protein Biomarker in the Prognosis of Patients with Acute Spinal Cord Injury

Abstract Introduction The role of some biomarkers such as S100 beta (S100B) has been somewhat known in determining the severity of primary acute spinal cord injury (SCI), and today, it has been the basis of various relevant studies. Therefore, this study estimates the S100B level in serum and cerebrospinal fluid (CSF) in patients with spinal injuries. Methods This was a descriptive-analytic study. In this study, 31 patients with acute SCI referred to Sari Imam Khomeini Hospital, Iran, were recruited. Patients were divided into two groups of complete and incomplete SCI according to the American Spinal Injury Association (ASIA). The S100B concentrations in serum and CSF levels were compared between the two groups. Result There was only significant positive correlation between S100B CSF concentration and complete SCI based on the ASIA criterion, meaning that in cases of complete SCI the S100B CSF concentration was significantly increased correlation coefficient (CC) (cc = 0.529 and p = 0.002). Based on the results of serum S100B protein concentration, 14.70 ng/dL with a sensitivity of 66.7% and specificity of 55% was determined as cutoff for complete SCI. Also, about the CSF S100B protein level variable, concentration of 342.18 ng/dL with 100% sensitivity and 64% specificity was determined as cutoff for complete injury. Conclusion The results of this unique study have shown that S100B were useful markers for predicting the prognosis of patients with acute SCI and cutoff points determined for serum and especially CSF concentrations can differentiate complete and incomplete SCI.

Evaluation of the brain cellular damage during liver transplantations.

Neuroinflammation in patients undergoing major surgery can lead to neuronal damage, and neuronal damage can be detected through the measurement of biochemical markers of brain damage. S100 beta (S100 β), neuron-specific enolase (NSE), and glial fibrillary acidic protein (GFAP) levels are considered good biomarkers to detect brain damage that emerged with neurotoxicity. To evaluate neuronal damage during liver transplantations. After approval of the ethics committee and patient consents, preoperative and postoperative cognitive functions of 33 patients undergoing liver transplantation were measured using the Mini Mental State Examination (MMSE), whereas simultaneous neuronal damage was evaluated through the measurement of S100β, NSE, and GFAP levels. There was no statistically significant difference between preoperative and postoperative MMSE. There was a statistically significant decrease in postoperative GFAP (P < 0.05) and a statistically significant increase in NSE (P < 0.05) compared to preoperative values. The decrease in S100β (P > 0.05) level was statistically insignificant. Neuroprotective approaches in anesthesia protocol protect patients from brain damage during liver transplantation and prevent the development of postoperative cognitive dysfunction. Since the significant increase in NSE levels during liver transplantations was deemed to have been associated with causes other than neuronal damage, NSE should not be evaluated as a marker of brain damage in these operations.

Early prognostication of ischemic stroke using computed tomography perfusion and S100 beta level

Background Early outcome prediction in ischemic stroke is a crucial concern for clinicians for proper decisions to reduce morbidity and mortality. The present study aimed to compare between computed tomography (CT) perfusion, National Institutes of Health Stroke Scale (NIHSS), and S100β for early outcome prediction. Patients and methods The study was carried out on 50 adult patients with acute ischemic stroke, classified into two groups according to modified Rankin score into group I (favorable outcome) and group II (unfavorable outcome). CT-perfusion was done on admission, NIHSS was calculated on admission, and blood was withdrawn on admission and third day for S100β. Results Infarction core size and the penumbra size were larger significantly in unfavorable-outcome group (P&lt;0.001). Also, S100β levels and NIHSS on admission were higher in group 2 than group 1 significantly (P&lt;0.001, P=0.001, respectively). Area under the curves were 0.787 for NIHSS score, 0.877 for S100β level, and 0.844 for penumbra size. A combination between penumbra size, S100β, and NIHSS to predict outcome. The receiver operating characteristic curve yielded an area under the curve of 0.905 (P&lt;0.001). Furthermore, the comparison between a combination of penumbra size, S100β, NIHSS on admission, and the final infarct in noncontrast CT on day 3 had a significant positive correlation coefficient (r=0.577, P&lt;0.001). Conclusion We suggest that higher NIHSS score on admission, large core and penumbra size, and high S100β level are independent early predictors of the functional outcome for acute ischemic-stroke patients. Moreover, detecting cases with NIHSS score more than 19, S100β more than 241 pg/ml, core size more than 10.35 cm3, and penumbra size more than 17.9 cm3, can individually predict unfavorable functional outcome in acute ischemic-stroke patients. Hence, using these cutoffs in combination might predict the outcome in a more precise manner.

Clinical efficacy of combined use of Xuebijing and mild hypothermia therapy for the treatment of severe traumatic brain injury, and its effect on patient mortality and complications

Purpose: To investigate the clinical efficacy of combined use of Xuebijing and mild hypothermia therapy in severe traumatic brain injury (TBI), and its effect on mortality and incidence of complications.&#x0D; Methods: Eighty-six severe TBI patients admitted to The Fourth People's Hospital of Chongqing were selected. Patients were randomly and equally assigned to control group (COG) who received conventional treatment, and study group (EXG) given a combination of Xuebijing and mild hypothermia therapy. Relevant clinical indicators and therapeutic effects were compared.&#x0D; Results: Post-treatment levels of inflammatory indices, including procalcitonin (PCT), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly reduced, with lower levels in EXG (p &lt; 0.05). Between-group differences were seen in human leukocyte antigen-DR isotype (HLA-DR), CD3+, CD4+, CD8+, and C3 indicators (p &lt; 0.05). EXG had significantly lower protein expression levels of neuron-specific enolase (NSE) and S100 beta than COG (p &lt; 0.05). After treatment, plasma protein levels of coagulation indices, viz, prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower than pre-treatment levels, with even much lower levels in EXG (p &lt; 0.05). There were reduced incidence of lung infection, acute gastrointestinal injury, acute respiratory distress syndrome (ARDS) and hypernatremia (p &lt; 0.05). More patients had better recovery in EXG (p &lt; 0.05) than in control group.&#x0D; Conclusion: The combined therapy improves the prognosis of severe TBI, lowers the levels of inflammatory factors, ameliorates plasma coagulation, and enhances immunity with a high degree of safety. However, further clinical trials should be undertaken prior to application in clinical practice

Serum S100B correlates with health-related quality of life and functional outcome in patients at 1 year after aneurysmal subarachnoid haemorrhage

BackgroundEarly, objective prognostication after aneurysmal subarachnoid haemorrhage (aSAH) is difficult. A biochemical marker would be desirable. Correlation has been found between levels of the protein S100 beta (S100B) and outcome after aSAH. Timing and clinical usefulness are under investigation.MethodsEighty-nine patients admitted within 48 h of aSAH were included. Modified ranking scale (mRS), EuroQoL health-related quality of life measure (EQ-5Dindex) and EuroQoL visual analogue scale (EQ-VAS) values were evaluated after 1 year. S100B was measured in blood samples collected at admission and up to day 10.ResultsS100B correlated significantly with EQ-5Dindex and mRS, but not EQ-VAS at 1 year after aSAH. A receiver operating characteristic analysis for peak S100B values (area under the curve 0.898, 95% confidence interval 0.828–0.968, p < 0.0001), with a cutoff of 0.4 μg/l, yielded 95.3% specificity and 68% sensitivity for predicting unfavourable outcome. Dichotomized S100B (> 0.4 μg/l vs ≤ 0.4 μg/l), age and Hunt and Hess grading scale score (HH) were associated with unfavourable mRS outcome in univariate logistic regression analysis. Dichotomized S100B was the only variable independently correlated with unfavourable mRS outcome in a multivariate logistic regression analysis.ConclusionsFor the first time, S100B was shown to correlate with mRS and health-related quality of life at 1 year after aSAH. Peak S100B can be used as a prognostic factor for unfavourable outcome measured as dichotomized mRS after aSAH. A peak value cutoff of 0.4 μg/l is suggested. Ethical approval no: 2013/366-31, 4th of February 2014.

Serum neuron-specific enolase: a new tool for seizure risk monitoring after status epilepticus.

There is a need for accurate biomarkers to monitor electroencephalography (EEG) activity and assess seizure risk in patients with acute brain injury. Seizure recurrence may lead to cellular alterations and subsequent neurological sequelae. Whether neuron-specific enolase (NSE) and S100-beta (S100B), brain injury biomarkers, can reflect EEG activity and help to evaluate the seizure risk was investigated. Eleven patients, admitted to an intensive care unit for refractory status epilepticus, who underwent a minimum of 3days of continuous EEG concomitantly with daily serum NSE and S100B assays were included. At 103days the relationships between serum NSE and S100B levels and two EEG scores able to monitor the seizure risk were investigated. Biochemical biomarker thresholds able to predict seizure recurrence were sought. Only NSE levels positively correlated with EEG scores. Similar temporal dynamics were observed for the time courses of EEG scores and NSE levels. NSE levels above 17ng/ml were associated with seizure in 71% of patients. An increase of more than 15% of NSE levels was associated with seizure recurrence in 80% of patients. Our study highlights the potential of NSE as a biomarker of EEG activity and to assess the risk of seizure recurrence.

NRGN, S100B and GFAP levels are significantly increased in patients with structural lesions resulting from mild traumatic brain injuries

ObjectiveTo determine whether serum neurogranin (NRGN), glial fibrillary acidic protein (GFAP), and calcium-binding protein S100 beta (S100B) levels are associated with traumatic intracranial lesions compared to computed tomography (CT) findings of patients with mild traumatic brain injury (mTBI). Patients and MethodsThe cross-sectional study cohort included 48 patients who were admitted to the Emergency Department with a complaint of mTBI, a Glasgow Coma Scale score of 14–15, and at least one symptom of head trauma (i.e., post-traumatic amnesia, nausea or vomiting, post-traumatic seizures, persistent headache, and transient loss of consciousness). Blood samples and CT scans were obtained for all patients within 4 h of injury. Age-matched patients without intracranial traumatic pathology (CT-) were recruited as a control group. Blood samples were measured for NRGN, GFAP, and S100B levels. ResultsOf 48 patients, 24 were CT + and had significantly higher serum NRGN (5.79 vs. 2.95 ng/mL), GFAP (0.59 vs.0.36 ng/mL), and S100B (1.72 vs.0.73 μg/L) levels than those who were CT- (p = 0.001, p = 0.026, and p < 0.001, respectively). ROC curves showed that NRGN, GFAP, and S100B levels were sufficient to distinguish traumatic brain injury in patients with mTBI. At the cut-off value for NRGN of 1.87 ng/mL, sensivity was 83.3%, and specificity was 58.3%. At the cut-off value for GFAP of 0.23 ng/mL, sensivity was 75% and specificity was 62.5%. The optimal cut-off value for S100B was 0.47 μg/L (95.8% sensitivity and 62.5% specificity). ConclusionThis is the first study to evaluate NRGN in human serum after mTBI. We confirmed that NRGN levels were significantly higher in CT + patients than CT- patients in the mTBI patient population. Future studies of larger populations and different age groups (especially pediatric) can help reduce the number of CT scans as a reliable and noninvasive diagnostic tool for evaluating NRGN protein levels in mTBI patients with a low probability of intracranial lesions.

Blood–Brain Barrier Dysfunction Assessed By Protein S-100 Beta Levels in Cirrhotic Patients

Background and Aims: The protein S-100 beta (PS-100) is a small dimeric cytosolic protein synthetized in astrocytes and Schwann cells. High serum levels of PS-100 are associated with brain lesions and altered blood-brain barrier permeability in traumatic brain injury, ischemic stroke, cerebral tumors and subarachnoid hemorrhage. Early brain damage has been detected in patients with cirrhosis. We hypothesized that those insults could be detected by the PS-100 serum levels (normal values < 0.10 μg/L). Hence, the aim of the present study was to assess PS-100 levels in cirrhotic patients, and compare them to PS-100 levels in non-cirrhotic patients followed up in the same department for initial workup of elevated liver enzymes (controls). Methods: We prospectively included a population of cirrhotic patients admitted for complication of cirrhosis in ICU and controls. Baseline data were recorded and levels of ammonemia and PS-100 determined at admission. Overt HE was diagnosed as a West-Haven score ranging between 2 and 4. Results Between October 2013 and October 2014, 124 cirrhotic patients (mean age: 63 years, male gender: 73%, etiology of cirrhosis: alcoholic 51%, viral 25%, other 24%, Child–Pugh 11 [8–12], MELD score 21 [14–26]) and 79 non-cirrhotic patients (mean age: 63 years, male 59%, etiology of elevated liver enzymes: alcoholic 5%, viral 44%, NASH 38%, other 13%, mean Fibroscan: 5.3 kPa, mean FibroTest: 0.15) were included. Among cirrhotic patients, 40 patients (33%) displayed HE at admission and 50 (41%) had an infection. Mean PS-100 level were 0.15 ± 0.01 for cirrhotic patients and 0.07 ± 0.01 for non-cirrhotic patients (P < 0.0001). In cirrhotic patients, PS-100 was correlated to AST (P = 0.0027), bilirubin (P = 0.0001), Child–Pugh score (P = 0.001) and MELD (P = 0.0004) and inversely correlated to albumin (P = 0.04), sodium (P = 0.01), PTT (P = 0.001), and FV (P = 0.011). PS-100 levels were not correlated to the presence of overt HE nor to infection. In multivariate analysis, levels of PS-100 were independently associated with MELD score (P = 0.0006), whereas overt HE was associated to hyperammonemia (P = 0.002) and the presence of infection (P = 0.008) but not to PS-100 levels. Conclusion: Patients with cirrhosis display neurological insult or blood–brain barrier dysfunction even in the absence of overt HE. Brain damage is more frequent in patients with advanced liver disease. The authors have none to declare.

Perioperative time course of matrix metalloproteinase-9 (MMP-9), its tissue inhibitor TIMP-1 & S100B protein in carotid surgery.

Background & objectives:Ischaemic stroke is a life burdening disease for which carotid endarterectomy (CEA) is considered a gold standard intervention. Pro-inflammatory markers like matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) and S-100 Beta (S100B) may have a role in the early inflammation and cognitive decline following CEA. This study was aimed to describe the perioperative time courses and correlations between of MMP-9, TIMP-1 and S100B following CEA.Methods:Fifty four patients scheduled for CEA were enrolled. Blood samples were collected at four time points, T1: preoperative, T2: 60 min after cross-clamp release, T3: first postoperative morning, T4: third postoperative morning. Twenty atherosclerotic patients were included as controls. Plasma MMP-9, TIMP-1 and S100B levels were estimated by ELISA.Results:TIMP-1 was decreased significantly in the CEA group (P<0.01). Plasma MMP-9 was elevated and remained elevated from T1-4 in the CEA group (P<0.05) with a marked elevation in T3 compared to T1 (P<0.05). MMP-9/TIMP-1 was elevated in the CEA group and increased further by T2 and T3 (P<0.05). S100B was elevated on T2 and decreased on T3-4 compared to T1.Interpretation & conclusions:Our study provides information on the dynamic changes of MMP-9-TIMP-1 system and S100B in the perioperative period. Preoperative reduction of TIMP-1 might be predictive for shunt requirement but future studies are required for verification.

Blood-brain barrier dysfunction assessed by protein S-100 beta levels in cirrhotic patients in ICU

The protein S-100 beta (PS-100) is a small dimeric cytosolic protein synthetized in astrocytes and Schwann cells. High serum levels of PS-100 are associated with brain lesions and altered blood-brain barrier permeability in traumatic brain injury, ischemic stroke, cerebral tumors and subarachnoid hemorrhage. Early brain damage has been detected in patients with cirrhosis. We hypothesized that those insults could be detected by the PS-100 serum levels (normal values < 0.10 µg/L).

Serum S-100β and NSE levels after off-pump versus on-pump coronary artery bypass graft surgery.

BackgroundWe aimed to evaluate serum levels of S-100 beta (S-100β) and neuron specific enolase (NSE) in patients with coronary heart disease (CHD) after off-pump versus on-pump coronary artery bypass graft (CABG) surgery.MethodsThe PubMed (~2013) and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. After extraction of relevant data from selected studies, meta-analyses were conducted using STATA software (Version 12.0, Stata Corporation, College Station, Texas USA). Possible sources of heterogeneity were examined through univariate and multivariate meta-regression analyses and verified by Monte Carlo Simulation.ResultsEleven studies with a total of 411 CHD patients met the inclusion criteria. Our meta-analysis showed no significant difference in serum S-100β and NSE levels between the on-pump group and the off-pump group before surgery. In the on-pump group, there was a significant difference in serum S-100β levels of CHD patients between before and after surgery, especially within the first 24 h after surgery. Furthermore, in the on-pump group, there was a significant difference in serum NSE levels of CHD patients between before and after surgery, particularly at 0 h after surgery. In the off-pump group, there was an obvious difference in serum S-100β levels between before and after surgery, especially within 24 h after surgery. Our results also demonstrated that serum S-100β and NSE levels of CHD patients in the on-pump group were significantly higher than those of patients in the off-pump group, especially within 24 h after surgery.ConclusionsOur findings provide empirical evidence that off-pump and on-pump CABG surgeries may increase serum S-100β and NSE levels in CHD patients, which was most prominent within 24 h after on-pump CABG surgery.

P0141 : Blood-brain barrier dysfunction assessed by Protein S-100 beta levels in cirrhotic patients

P0141 : Blood-brain barrier dysfunction assessed by Protein S-100 beta levels in cirrhotic patients

Reduced intraepidermal nerve fiber density in patients with chronic ischemic pain in peripheral arterial disease

Chronic ischemic pain in peripheral arterial disease (PAD) is a leading cause of pain in the lower extremities. A neuropathic component of chronic ischemic pain has been shown independent of coexisting diabetes. We aimed to identify a morphological correlate potentially associated with pain and sensory deficits in PAD. Forty patients with symptomatic PAD (Fontaine stages II-IV), 20 with intermittent claudication (CI), and 20 with critical limb ischemia (CLI) were enrolled; 12 volunteers served as healthy controls. All patients were examined using pain scales and questionnaires. All study participants underwent quantitative sensory testing (QST) at the distal calf and skin punch biopsy at the distal leg for determination of intraepidermal nerve fiber density (IENFD). Additionally, S100beta serum levels were measured as a potential marker for ischemic nerve damage. Neuropathic pain questionnaires revealed slightly higher scores and more pronounced pain-induced disability in CLI patients compared to CI patients. QST showed elevated thermal and mechanical detection pain thresholds as well as dynamic mechanical allodynia, particularly in patients with advanced disease. IENFD was reduced in PAD compared to controls (P<0.05), more pronounced in the CLI subgroup (CLI: 1.3±0.5fibers/mm, CI: 2.9±0.5fibers/mm, controls: 5.3±0.6fibers/mm). In particular, increased mechanical and heat pain thresholds negatively correlated with lower IENFD. Mean S100beta levels were in the normal range but were higher in advanced disease. Patients with chronic ischemic pain had a reduced IENFD associated with impaired sensory functions. These findings support the concept of a neuropathic component in ischemic pain.

Modeling Serum Level of S100β and Bispectral Index to Predict Outcome After Cardiac Arrest

This study was designed to evaluate multimodal prognostication in patients after cardiac arrest (CA). Accurate methods to predict outcome after CA are lacking. Seventy-five patients with CA treated with therapeutic hypothermia after cardiac resuscitation were enrolled in this prospective observational study. Serum levels of neuron-specific enolase (NSE) and neuron-enriched S100 beta (S100β) were measured 48 h after CA. Bispectral index (BIS) was continuously monitored during the first 48 h after CA. The primary endpoint was neurological outcome, as defined by the cerebral performance category (CPC) at 6-month follow-up: scores 1 or 2 indicated good outcome, and scores 3 to 5, poor outcome. The secondary endpoint was survival. A total of 46 (61%) patients survived at 6 months and 41 (55%) patients had CPC 1 or 2. Levels of NSE and S100β were higher in patients with poor outcomes compared with patients with good outcomes (4-fold and 10-fold, respectively; p < 0.001). BIS was lower in patients with poor outcomes (10-fold; p < 0.001). NSE, S100β, or BIS alone predicted neurological outcome, with areas under the receiver-operating characteristic curve (AUC) above 0.80. Combined determination of S100β and BIS had an incremental predictive value (AUC: 0.95). S100β improved discriminations based on BIS (p = 0.0008), and BIS improved discriminations based on S100β (p < 10(-5)). Patients with S100β level above 0.03 μg/l and BIS below 5.5 had a 3.6-fold higher risk of poor neurological outcome (p < 0.0001). S100β and BIS predicted 6-month mortality (log-rank statistic: 50.41; p < 0.001). Combined determination of serum level of S100β and BIS monitoring accurately predicts outcome after CA.

Troubleshooting the rat model of cardiopulmonary bypass: Effects of avoiding blood transfusion on long-term survival, inflammation and organ damage

IntroductionRat models of cardiopulmonary bypass (CPB) have been used to examine the mechanisms of associated organ damage and to test intervention strategies. However, these models only partly mimic the clinical situation, because of the use of blood transfusion and arterial inflow via the tail artery. Thus a model using arterial inflow in the aorta and a miniaturized CPB circuit without need of transfusion was validated by examining intra-procedure characteristics, mortality and the effects of CPB on biomarkers of inflammation and cerebral injury during 5days follow-up. MethodsMale Wistar rats (n=95) were anesthetized with isoflurane (2.5%) and fentanyl/midazolam during CPB. Animals were assigned to Control (n=6), Sham (n=40) or normothermic CPB (n=49) groups. Both Sham and CPB were cannulated in the aorta via the left carotid artery and in the right common jugular vein for access into the right heart. Extracorporeal circulation (ECC) was instituted for 60min only in CPB at a flow rate of 120mLkg−1min−1 employing a CPB circuit of 15ml primed with 6% hydroxyethyl starch 60mgml−1 solution. Rats were sacrificed at either 1h or 1, 2 or 5days after Sham or weaning from CPB. Plasma IL-6 and s100Beta levels were measured and blood cell counts were performed. ResultsMortality in CPB animals (3 out of 49) and Sham (4 out of 40) did not differ (chi-square=0.46, dF=1, P>0.5). Compared to baseline (1.87±0.46∗10^9cells/L), Sham procedure (cannulation and anesthesia) significantly increased blood neutrophil count at the end of the period matching ECC (6.34±2.36∗10^9cells/L, P<0.05). CPB induced neutrophilia which persisted during 24h recovery. Also, CPB caused a rapid and prominent increase in plasma IL-6 from the first hour of the postoperative period (~1200pg/ml) with continuation (50–90pg/ml) up to 5th day of recovery. S100Beta levels were above detection level only in 3 out of 42 samples from CPB animals. DiscussionOur rat model of CPB without homologous blood transfusion produces a reproducible and reliable systemic inflammatory response, with low mortality rates on long term follow up. The model more closely mimics the human situation in respect to arterial inflow site and avoidance of blood transfusion. Thus, our CPB model is suitable to study its influence on systemic inflammation, ischemia–reperfusion injury, microcirculation and vascular dysfunction in vivo, and to evaluate potential therapeutic interventions.

Biomarcadores na encefalopatia séptica: revisão sistemática dos estudos clínicos

ObjectiveThe aim of this study was to systematically review the importance of neuron-specific enolase and S100 beta for diagnosing and monitoring septic encephalopathy. MethodsA PubMed database search was performed to identify studies that evaluated S100 beta and neuron-specific enolase serum levels in patients with sepsis and that were published between January 2000 and April 2012. Only human studies that employed an additional method of neurological assessment were selected. ResultsNine studies were identified, seven of which associated high concentrations of S100 beta and neuron-specific enolase with the development of septic encephalopathy. Four studies also associated these concentrations with increased mortality. However, two studies did not find such an association when they evaluated S100 beta levels, and one of these studies did not observe a correlation between neuron-specific enolase and septic encephalopathy. ConclusionS100 beta and neuron-specific enolase are promising biomarkers for diagnosing and monitoring patients with septic encephalopathy, but more research is necessary.

Therapeutic time window of hypothermia is broader than cerebral artery flushing in carotid saline infusion after transient focal ischemic stroke in rats

Object: Intracarotid cold saline infusion (ICSI) protects against ischemic stroke not only due to the resulting hypothermia, but also as a result of the cerebral artery flushing. To assess the relative benefit of hypothermia and cerebral artery flushing in neuroprotection, hypothermic and normothermic saline infusions were administrated over a serial time points after the initiation of reperfusion in a rat ischemia model.Methods: Ischemic strokes were induced in Sprague–Dawley rats (n = 115) by occluding the middle cerebral artery for 2 hours using an intraluminal filament. In the hypothermic groups, the brain temperature was lowered to 33–34°C for 20 minutes by ICSI at three time points (0, 1, and 2 hours) after reperfusion. Correspondingly, in the normothermic groups, the brain temperature was maintained at normal levels during intracarotid normothermic saline infusion (INSI) for 20 minutes at the same time points. After 48-hour reperfusion, infarct sizes and brain water contents were determined using 2,3,5-triphenyltetrazolium chloride (TTC) staining and the dry–wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100beta, and matrix metalloproteinase 9 (MMP9) in the serum were measured by enzyme-linked immunoassay (ELISA). Neurological deficits were also evaluated.Results: Immediate infusion after the onset of reperfusion (0 hour) did not result in significant difference for reductions of infarct sizes, neurological deficits or S100beta serum levels between ICSI and INSI groups, compared with the non-infusion group. However, brain water content and NSE serum level were significantly lower in the ICSI group than the non-infusion group. When the infusions were started 1 hour after reperfusion, both ICSI and INSI infusions still reduced the infarct sizes, but only ICSI significantly decreased the brain water content, neurological deficits and S100beta serum level. All therapeutic effects of INSI disappeared when infusions were started 2 hours after reperfusion, whereas infarct size, neurological deficits and S100beta serum level were still reduced significantly in ICSI group, compared with the non-infusion group.Conclusions: The neuroprotection of hypothermia and cerebral artery flushing induced by selective carotid infusion after ischemia weakens as the length of time between the reperfusion and infusion increases. The therapeutic time window of brain hypothermia induced by cold saline infusion is broader than cerebral artery flushing induced by normothermic saline infusion.

Comparison of the effects of pulsatile cardiopulmonary bypass, non-pulsatile cardiopulmonary bypass and off-pump coronary artery bypass grafting on the inflammatory response and S-100beta protein

We aimed to investigate the effects of off-pump coronary artery bypass grafting, pulsatile cardiopulmonary bypass, and non-pulsatile cardiopulmonary bypass techniques on the inflammatory response and the central nervous system in the current study. A total of 32 patients who were scheduled for elective coronary artery bypass graft surgery were included in the study. The patients were allocated into three different groups according to the perfusion techniques used during the cardiopulmonary bypass procedure as follows: off-pump coronary artery bypass grafting group (n=10); pulsatile cardiopulmonary bypass group (n=11); and non-pulsatile cardiopulmonary bypass group (n=11). Serum interleukin-6, interleukin-8, tumor necrosis factor-alpha and S-100beta levels were measured preoperatively, and at 0, 6, and 24 hours postoperatively. The postoperative increase in the levels of interleukin-6 and interleukin-8 was significantly lower in the off-pump group compared to the other two groups (p<0.05), while there was no significant difference in tumor necrosis factor-alpha levels between the groups. Postoperative S-100β levels, an indicator of cerebral injury, was significantly lower in the off-pump CABG group compared to the other two groups (p<0.05). We found that off-pump coronary artery bypass grafting had less negative effects on inflammatory response and central nervous system compared to pulsatile cardiopulmonary bypass and non-pulsatile cardiopulmonary bypass techniques.

HOXC11–SRC-1 regulation of S100beta in cutaneous melanoma: new targets for the kinase inhibitor dasatinib

Background:Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined.Methods:Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays.Results:Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11–SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo.Conclusion:We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.

Effects of a Short-acting β1 Receptor Antagonist Landiolol on Hemodynamics and Tissue Injury Markers in Patients With Subarachnoid Hemorrhage Undergoing Intracranial Aneurysm Surgery

Sympathetic activation after subarachnoid hemorrhage (SAH) can induce tachycardia as well as cardiac and brain injury. We examined the effects of beta1 receptor antagonist landiolol on hemodynamics and the levels of tissue injury markers in patients with SAH. Fifty-six SAH patients undergoing intracranial aneurysm surgery with tachycardia (>or=90 beats per minute) randomly allocated to landiolol (L) or control (C) group were examined. In L group, landiolol was continuously administered during anesthesia. In C group, landiolol was not administered except bolus dose used in cases that exhibited uncontrolled tachycardia. Hemodynamics, the incidence of electrocardiographic abnormality, and levels of B-type natriuretic peptide, troponin T, S-100beta, 8-Hydroxy-2'-deoxyguanosine, interleukin-6 (IL-6), and IL-1 receptor antagonist were compared. Heart rate values from time of intubation to the end of anesthesia were significantly lower in L group than in C group, whereas blood pressure was similar between the groups. Although the incidence of bradycardia (<60 beats per minute) was significantly higher in L group than in C group (57% vs. 18%, respectively), bradycardia could be recovered without any adverse effects. The serum S-100beta levels 24 hours after operation were significantly lower in L group than in C group, whereas there were no significant differences in the incidence of electrocardiographic abnormality and levels of B-type natriuretic peptide, troponin T, 8-Hydroxy-2'-deoxyguanosine, IL-6, and IL-1 receptor antagonist between groups. We conclude that landiolol can be effectively used in the treatment of tachycardia in SAH patients and significantly reduced the serum S-100beta levels 24 hours after the operation.