Effect of green tea extract on arterial stiffness, lipid profile and sRAGE in patients with type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled trial.

Type 2 diabetes mellitus (T2DM) is associated with premature atherosclerosis and arterial stiffening due to the accumulation of advanced glycation end-products in vessel walls. Green tea polyphenols are considered cardio-protective substances. In this randomised double-blind placebo-controlled trial (NCT02627898), we evaluated the effect of Green tea extract on arterial stiffness parameters, lipids, body composition and sRAGE levels. Twenty normotensive patients with T2DM treated with the standard therapy and statins, mean age 53.2 ± 9.4 years and mean BMI 30.1 ± 4.5 kg/m2, were randomised to receive a daily dose of 400 mg of green tea extract (polyphenols ≥90%, EGCG ≥45%) or placebo for 12 weeks. Compared to placebo, administration of green tea extract decreased central augmentation index (-3.05 ± 10.8% vs. 6.7 ± 0.1%, p = .04). These findings suggest that green tea extract could be used as an adjunct to the standard therapy to improve arterial stiffness in T2DM.

Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation.

Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post-medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide-stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.

S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass.

OBJECTIVE: The present study is to describe the clinical impact of S100 and S100ß for the evaluation of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass (CPB). METHODS: Quantitative results of S100 and S100ß reported in the literature of the year range 1990-2014 were collected, screened and analyzed. RESULTS: Cerebrospinal fluid and serum S100 levels showed a same trend reaching a peak at the end of CPB. The cerebrospinal fluid/serum S100 ratio decreased during CPB, reached a nadir at 6 h after CPB and then increased and kept high untill 24 h after CPB. Serum S100 at the end of CPB was much higher in infant than in adults, and in on-pump than in off-pump coronary artery bypass patients. ∆S100 increased with age and CPB time but lack of statistical significances. Patients receiving an aorta replacement had a much higher ∆S100 than those receiving a congenital heart defect repair. Serum S100ß reached a peak at the end of CPB, whereas cerebrospinal fluid S100 continued to increase and reached a peak at 6 h after CPB. The cerebrospinal fluid/serum S100ß ratio decreased during CPB, increased at the end of CPB, peaked 1 h after CPB, and then decreased abruptly. The increase of serum S100ß at the end of CPB was associated with type of operation, younger age, lower core temperature and cerebral damages. ∆S100ß displayed a decreasing trend with age, type of operation, shortening of CPB duration, increasing core temperature, lessening severity of cerebral damage and the application of intervenes. Linear correlation analysis revealed that serum S100ß concentration at the end of CPB correlated closely with CPB duration. CONCLUSION: S100 and S100ß in cerebrospinal fluid can be more accurate than in the serum for the evaluations of cerebral damage in cardiac surgery. However, cerebrospinal fluid biopsies are limited. But serum S100ß and ∆S100ß seem to be more sensitive than serum S100 and ∆S100. The cerebral damage in cardiac surgery might be associated with younger age, lower core temperature and longer CPB duration during the operation. Effective intervenes with modified CPB circuit filters or oxygenators and supplemented anesthetic agents or priming components may alleviate the cerebral damage.

EGCG-rich green tea extract stimulates sRAGE secretion to inhibit S100A12-RAGE axis through ADAM10-mediated ectodomain shedding of extracellular RAGE in type 2 diabetes.

The receptor for advanced glycation of end products (RAGE) plays a critical role in the progression of type 2 diabetes (T2D). Soluble RAGE (sRAGE) is one of the RAGE variants, which acts as a decoy domain receptor and competes with RAGE, thus contributing to prevention of T2D. In this study, we conducted clinical trials of (-)-epigallocatechin-3-gallate (EGCG) rich green tea extract (300-900 mg/day) to investigate the effect of EGCG on relationship between S100A12 RAGE ligand and diverse sRAGE in T2D. Moreover, mechanism of sRAGE production also confirmed in vitro. Our data indicated that EGCG could stimulate sRAGE circulation but inhibited RAGE ligand in T2D, and ADAM10-mediated ectodomain shedding of extracellular RAGE was mainly involved in EGCG-stimulated sRAGE circulation. The present evidence indicates that EGCG has a potential to block S100A12-RAGE axis by stimulating sRAGE production through ADAM10-mediated ectodomain shedding of extracellular RAGE. Therefore, EGCG contributes to nutritional strategies for diabetes, not only because of its efficient antioxidant activity to scavenge free radicals, but also because of its ability stimulating sRAGE release in the circulation. Additionally, ADAM10-induced ectodomain shedding of extracellular RAGE leading to sRAGE circulation should be a potential of passive mechanism of sRAGE production to block S100A12-RAGE axis-related pathogenesis of proinflammation and diabetes.

High-dose propofol reduces S-100ß protein and neuron-specific enolase levels in patients undergoing cardiac surgery.

OBJECTIVES: In a variety of experimental models, propofol has been shown to protect the brain. It was hypothesized that a clinically achievable high dose of propofol would induce cerebral protective effects in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The authors investigated the effects of different target plasma concentrations of propofol on cerebral injury by measuring serum S-100ß protein and neuron-specific enolase (NSE) levels in patients undergoing single-valve replacement with CPB. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-two patients undergoing single-valve replacement with CPB. INTERVENTIONS: Patients were randomly divided into 3 groups (n = 14 each). Each group received a target-controlled infusion of propofol with plasma concentrations of 1.8 µg/mL (low dose, Group-L), 2.4 µg/mL (medium dose, Group-M), or 3.2 µg/mL (high dose, Group-H). The propofol target concentrations were unchanged throughout the surgery. MEASUREMENTS AND MAIN RESULTS: In all 3 groups of patients, at all time points after CPB, the plasma S-100ß protein and NSE levels, which served as biochemical markers of brain damage, were significantly higher than the preoperative levels (p<0.05). Group-H showed significant decreases in S-100ß protein and NSE compared with Group-L (p< 0.05). CONCLUSION: In the range of commonly used clinical concentrations, administration of a high dose of propofol during CPB attenuated the biochemical markers of brain damage as compared with low-dose propofol anesthesia.

Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is a common form of focal epilepsy. Serum biomarkers to predict cognitive performance in TLE patients without psychiatric comorbidities and the link with gray matter (GM) atrophy have not been fully explored. METHODS: Thirty-four patients with TLE and 34 sex - and age-matched controls were enrolled for standardized cognitive tests, neuroimaging studies as well as measurements of serum levels of heat shock protein 70 (HSP70), S100ß protein (S100ßP), neuronal specific enolase (NSE), plasma nuclear and mitochondrial DNA levels. RESULTS: Compared with the controls, the patients with TLE had poorer cognitive performances and higher HSP70 and S100ßP levels (p < 0.01). The patients with higher frequencies of seizures had higher levels of HSP70, NSE and S100ßP (p < 0.01). Serum HSP70 level correlated positively with duration of epilepsy (σ = 0.413, p < 0.01), and inversely with memory scores in the late registration (σ = -0.276, p = 0.01) and early recall score (σ = -0.304, p = 0.007). Compared with the controls, gray matter atrophy in the hippocampal and parahippocampal areas, putamen, thalamus and supplementary motor areas were found in the patient group. The HSP70 levels showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age. CONCLUSIONS: Our results suggest that serum biomarkers were predictive of higher frequencies of seizures in the TLE group. HSP70 may be considered to be a stress biomarker in patients with TLE in that it correlated inversely with memory scores and hippocampal volume. In addition, the symmetric extratemporal atrophic patterns may be related to damage of neuronal networks and epileptogenesis in TLE.

The current status of S-100B as a biomarker in melanoma.

Melanoma is the most malignant type of all skin cancer types. It causes over 75% of all skin cancer related mortality. In the Netherlands, the total number of new diagnosed melanoma patients is expected to increase from 2400 patients in 2000 to 4800 patients in 2015. After surgical treatment, 20-28% of melanoma patients present with loco-regional recurrence, 26-60% with regional recurrences, and 15-50% with distant metastases. Early detection of lymph node (micro) metastases by means of a sentinel lymph node biopsy (SLNB) is therefore of crucial importance since early lymph node dissection decrease treatment morbidity and improve overall survival. However when patients present with palpable nodes, given the heterogeneity in survival, the suspicion rises that numerous patients have a form of subclinical dissemination, which can remain undetected by current modern imaging methods. Biomarkers could illuminate on this matter, although there is very little understanding of their biological significance. It can be expected that the strongest biological markers are surrogates of key biological events. The protein S-100B seems to be the best analyzed biomarker in melanoma. It has the potential to identify high-risk stage III melanoma patients who may benefit from adjuvant systematic treatment. In the stratification of new adjuvant therapeutic trials in patients with loco-regional recurrences, we therefore recommend the use of S-100B in the stratification. Since an effective (adjuvant) therapy for loco-regional metastatic and disseminated melanoma is recently introduced, the use of S-100B seems to alter dramatically in the near future.

Evaluation of the effect of one large dose of erythropoietin against cardiac and cerebral ischemic injury occurring during cardiac surgery with cardiopulmonary bypass: a randomized double-blind placebo-controlled pilot study.

Cardiac surgery and cardiopulmonary bypass (CPB) induce ischemia-reperfusion and subsequent cellular injury with inflammatory reaction. Clinical and experimental studies suggest that recombinant human erythropoietin (EPO) independently of its erythropoietic effect may be used as a cytoprotective agent against ischemic injury. We tested the hypothesis that one large dose of EPO administered shortly before CPB prevents the elevation of cardiac and cerebral ischemic blood markers as well as the systemic inflammatory response induced by cardiac surgery with CBP through this randomized double-blind placebo-controlled pilot trial. Fifty patients scheduled for coronary artery bypass graft (CABG) surgery with CPB were randomly allocated to EPO or control groups. EPO (800 IU/kg intravenously) or placebo (saline) was administered before CPB. The primary end point was to study the effect of EPO administration on several blood markers of myocardial and cerebral ischemia in relation to CABG with CPB. In both groups, surgery increased plasma concentrations of cardiac (troponin T, NT-proBNP, and creatine kinase MB) and cerebral (S100ß protein) markers ischemic as well as the pro-inflammatory marker interleukin-6. Compared with the placebo, EPO administration before CPB did not prevent an increase of all these markers following CPB. In conclusion, one large dose of EPO, given shortly before CPB, did not protect against cardiac and cerebral ischemia and inflammatory response occurring during CABG surgery with CPB. Although the long-term clinical implications remain unknown, the findings do not support use of EPO at this dose as a cytoprotective agent in patients undergoing cardiac surgery.

Preconditioning with repeated hyperbaric oxygen induces myocardial and cerebral protection in patients undergoing coronary artery bypass graft surgery: a prospective, randomized, controlled clinical trial.

OBJECTIVES: To evaluate the cerebral and myocardial protective effects of hyperbaric oxygen preconditioning in both on-pump and off-pump coronary artery bypass graft surgery. DESIGN: A prospective, randomized, single-blinded study including patients scheduled for elective on-pump or off-pump surgery between December 2007 and February 2009. SETTING: A tertiary care university teaching hospital. PARTICIPANTS: Forty-nine elective on-pump or off-pump coronary artery bypass graft surgery patients. INTERVENTIONS: Patients were randomized to either the control (15 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) or hyperbaric oxygen (HBO; 14 patients with on-pump procedure and 10 patients with off-pump procedure, respectively) groups. Patients in the HBO groups underwent preconditioning for 5 days before surgery. MEASUREMENTS AND MAIN RESULTS: On-pump coronary artery bypass graft surgery patients preconditioned with HBO had significant decreases in S100B protein, neuron-specific enolase, and troponin I perioperative serum levels compared with the on-pump control group. Postsurgically, patients in the on-pump HBO group had a reduced length of stay in the intensive care unit and a decreased use of inotropic drugs. Serum catalase activity 24 hours postoperatively was significantly increased compared with the on-pump control group. In the off-pump groups, there was no difference in any of the same parameters. CONCLUSIONS: Preconditioning with HBO resulted in both cerebral and cardiac protective effects as determined by biochemical markers of neuronal and myocardial injury and clinical outcomes in patients undergoing on-pump coronary artery bypass graft surgery. No protective effects were noted in off-pump coronary artery bypass graft surgery.

Potential role for S100A4 in the disruption of the blood-brain barrier in collagen-induced arthritic mice, an animal model of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation of the joints. RA has been shown to increase the morbidity of and mortality due to cardiovascular and cerebrovascular diseases. We recently reported that cerebrovascular permeability was increased in mice with collagen-induced arthritis (CIA), an animal model of RA. S100A4, a member of the S100 family, is up-regulated in synovial fluid and plasma from RA patients. This study was aimed at evaluating a role of S100A4 in the mediation of blood-brain barrier (BBB) dysfunction in CIA mice. CIA was induced by immunization with type II collagen in mice. Cerebrovascular permeability was assessed by measurement of sodium fluorescein (Na-F) levels in the brains of control and CIA mice. Serum S100A4 concentrations in control and CIA mice were measured by enzyme-linked immunosorbent assays (ELISA). Accumulation of Na-F in the brain and serum levels of S100A4 were increased in CIA mice. Increased S100A4 levels in the serum are closely correlated with hyperpermeability of the cerebrovascular endothelium to Na-F. We investigated whether S100A4 induces BBB dysfunction using mouse brain capillary endothelial cells (MBECs). S100A4 decreased the transendothelial electrical resistance and increased Na-F permeability in the MBECs. S100A4 reduced the expression of occludin, a tight junction protein, and stimulated p53 expression in MBECs. These findings suggest that S100A4 increases paracellular permeability of MBECs by decreasing expression levels of occludin, at least in part, via p53. The present study highlights a potential role for S100A4 in BBB dysfunction underlying cerebrovascular diseases in patients with RA.

Effect of electroacupuncture preconditioning on serum S100beta and NSE in patients undergoing craniocerebral tumor resection.

OBJECTIVE: To investigate the effect of electroacupuncture preconditioning on the serum level of S100 calcium-binding protein beta (S100beta) and neuron-specific enolase (NSE) in patients undergoing craniocerebral tumor operation. METHODS: A total of 32 patients, who would go through craniocerebral tumor resection under general anesthesia, were randomly assigned to two groups, 16 in each group. Patients in the electroacupuncture (EA) group received electroacupuncture on Fengfu acupoint (Du16) and Fengchi acupoint (GB20) for 30 min, 2 h before operation. The stimulus is 1-4 mA with a density wave frequency of 2/15 Hz. Patients in the control group received no pretreatment. Anesthesia was maintained with remifentanil at the dose of 4-8 mg/kg per hour, pumped intravenous drip of vecuronium at 1.0-2.0 microg/kg each hour, and discontinuous intravenous dripped with vecuronium bromide at 0.5-1 mg. The serum levels of S100beta and NSE were measured with ELISA before operation, before skin incision, after tumor removal, at the end of operation, and at 24 h after operation. RESULTS: The serum level of S100beta and NSE did not change before skin incision. The serum level of NSE increased significantly and the level of S100beta increased insignificantly after the tumor resection. The serum levels of S100beta and NSE in the EA group and the control group were 1.16+/-0.28 microg/L vs 1.47+/- 0.33 microg/L, 24.7+/-13.3 microg/L vs 31.4+/-14.1 microg/L at the end of the operation, respectively. Twenty-four h after operation, the correspondence indices were 1.18+/-0.31 microg/L vs 1.55+/-0.26 microg/L, and 25.5+/-12.4 microg/L vs 32.4+/- 11.7 microg/L. The two indices at these two time points were significantly increased than those before operation, respectively (P<0.05). At the end of the operation and 24 h post-operation, the serum levels of S100beta and NSE in the EA group were significantly lower than those in the control group (P<0.05). CONCLUSION: Electroacupuncture Fengchi and Fengfu for 30 min before craniocerbral tumor operation could decrease the serum level of S100beta and NSE, thus may have potential protective effect on brain damage, which needs to be further studied.

Serum levels of S100B and NSE proteins in Alzheimer's disease patients.

BACKGROUND: Alzheimer's disease is the most common dementia in the elderly, and the potential of peripheral biochemical markers as complementary tools in the neuropsychiatric evaluation of these patients has claimed further attention. METHODS: We evaluated serum levels of S100B and neuron-specific enolase (NSE) in 54 mild, moderate and severe Alzheimer's disease (AD) patients and in 66 community-dwelling elderly. AD patients met the probable NINCDS-ADRDA criteria. Severity of dementia was ascertained by the Clinical Dementia Rating (CDR) scale, cognitive function by the Mini Mental State Examination (MMSE), and neuroimage findings with magnetic resonance imaging. Serum was obtained from all individuals and frozen at -70 degrees C until analysis. RESULTS: By comparing both groups, serum S100B levels were lower in AD group, while serum NSE levels were the same both groups. In AD patients, S100B levels were positively correlated with CDR scores (rho = 0.269; p = 0.049) and negatively correlated with MMSE scores (rho = -0.33; P = 0.048). NSE levels decreased in AD patients with higher levels of brain atrophy. CONCLUSIONS: The findings suggest that serum levels of S100B may be a marker for brain functional condition and serum NSE levels may be a marker for morphological status in AD.

Stroke biomarkers: progress and challenges for diagnosis, prognosis, differentiation, and treatment.

BACKGROUND: Stroke is a devastating condition encompassing a wide range of pathophysiological entities that include thrombosis, hemorrhage, and embolism. Current diagnosis of stroke relies on physician clinical examination and is further supplemented with various neuroimaging techniques. A single set or multiple sets of blood biomarkers that could be used in an acute setting to diagnosis stroke, differentiate between stroke types, or even predict an initial/reoccurring stroke would be extremely valuable. CONTENT: We discuss the current classification, diagnosis, and treatment of stroke, focusing on use of novel biomarkers (either solitary markers or multiple markers within a panel) that have been studied in a variety of clinical settings. SUMMARY: The current diagnosis of stroke remains hampered and delayed due to lack of a suitable mechanism for rapid (ideally point-of-care), accurate, and analytically sensitive biomarker-based testing. There is a clear need for further development and translational research in this area. Potential biomarkers identified need to be transitioned quickly into clinical validation testing for further evaluation in an acute stroke setting; to do so would impact and improve patient outcomes and quality of life.

Serum S100A6 concentration predicts peritoneal tumor burden in mice with epithelial ovarian cancer and is associated with advanced stage in patients.

BACKGROUND: Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. METHODOLOGY AND PRINCIPAL FINDINGS: Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. CONCLUSIONS: S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers.

New markers of neonatal neurology.

Hypoxia-ischemia (H-I) constitutes the main phenomenon responsible for brain-blood barrier permeability modifications leading to cerebral vascular auto-regulation loss in newborns. Hypotension, cerebral ischemia, and reperfusion are the main events involved in vascular auto-regulation loss leading to cell death and tissue damage. Reperfusion could be critical since organ damage, particularly of the brain, may be amplified during this period. An exaggerated activation of vasoactive agents, of calcium mediated effects could be responsible for reperfusion injury (R-I), which, in turns, leads to cerebral hemorrhage and damage. These phenomena represent a common repertoire in newborns complicated by perinatal acute or chronic hypoxia treated by risky procedures such as mechanical ventilation, nitric oxide supplementation, brain cooling, and extracorporeal membrane oxygenation (ECMO). Despite accurate monitoring, the post-insult period is crucial, as clinical symptoms and standard monitoring parameters may be silent at a time when brain damage is already occurring and the therapeutic window for pharmacological intervention is limited. Therefore, the measurement of circulating biochemical markers of brain damage, such as vasoactive agents and nervous tissue peptides is eagerly awaited in clinical practice to detect high risk newborns. The present review is aimed at investigating the role of biochemical markers such as adrenomedullin, a vasoactive peptide; S100B, a calcium binding protein, activin A, a glycoprotein, in the cascade of events leading to I-R injury in newborns complicated by perinatal asphyxia.

[Effects of preconditioning and postconditioning with shenfu injection on cognitive function in patients after valve replacement under cardiopulmonary bypass].

OBJECTIVE: To investigate the effects of preconditioning and postconditioning with Shenfu Injection (SFI) on cognitive function in patients after valve replacement under extra-corporeal circulation. METHODS: Thirty-two patients prepared to receive valve replacement, aged 25-54 years, with heart function of II-III level, were randomly assigned to four groups, eight in each group. Patients in group E1 received SFI 1 mL/kg after intubation and before blocking the aorta; patients in group E2 received SFI 1 mL/kg after opening the aorta; patients in group E3 received SFI 0.5 mL/kg twice, at before blocking and after opening the aorta, respectively; and patients in group C received 1 mL/kg normal saline after intubation for control. All the medication was infused via pump. Venous blood samples were taken from the internal jugular venous bulb cannula for detecting plasma S100beta protein by ELISA at 6 different time points, i.e. after trachea intubation (T1), 10 min after cardiopulmonary bypass (CPB, T2), hypothermia stabilizing stage (T3), re-warming to 33 degrees C (T4), ending CPB (T5) and 1 h after ending CPB (T6). And patients' cognitive function was assessed for 4 times with mini-mental state examination (MMSE) scale, at the day before operation, and 1, 2, 7 days after operation. RESULTS: The elevation of S100beta plasma protein was lesser in the three E groups than that in group C (P < 0.05), and the lowest level was shown at T6 in Group E3 (P < 0.05). The highest incidence of cognitive dysfunction occurred in Group C one week after operation (P < 0.05). CONCLUSION: SFI may reduce the plasma level of S100B protein, maintain stable the structure and function of blood-brain barrier, it is favorable to the post-operational recovery of neurological function of patients, showing good brain protective effect. The optimal effect could be obtained by pump infusion of 0.5 mL/kg of SFI before aortic blocking and after aortic opening.

Jugular venous neurone specific enolase (NSE) increases following carotid endarterectomy under general, but not local, anaesthesia.

INTRODUCTION: Previous studies indicate that local (LA) rather than general anaesthesia (GA) for carotid endarterectomy (CEA) is associated with reflex hypertension and preservation of cerebral cytochrome oxidase after carotid clamping. The hypothesis that LA offers protection against ischaemic cerebral injury has been investigated by measuring ipsilateral jugular venous neurone specific enolase (NSE: neuronal glycolytic enzyme) and S-100B (glial cell protein) during and after CEA. METHODS: 27 patients with symptomatic carotid artery disease (70-99% stenosis) underwent CEA, 14 under LA and 13 under GA. Jugular venous blood samples were assayed for NSE and S-100B before carotid clamping and at 5min before and 5min, 2, 4, 6, 8, 12 and 24h after clamp release. RESULTS: No neurological complications occurred. S-100B levels were low and did not increase from baseline in either group. Pre-clamp NSE levels were similar in both groups (LA: 17.6 (15.2-20.7)microg/l, GA: 21.5 (11.3-26.2)microg/l; p=0.37) but increased significantly 2h after clamp release in GA patients (LA: 25.5 (16.6-27.8)microg/l, GA: 48.2 (31.4-61.3)microg/l, p=0.05) with a significant rise from baseline in GA patients (p=0.04). CONCLUSIONS: CEA performed under GA is associated with greater rises in jugular venous NSE, and hence cerebral injury, than CEA performed under LA.

Magnesium supplementation significantly reduces serum S100beta concentrations in patients who have undergone coronary artery bypass surgery.

UNLABELLED: Magnesium (Mg) plays an important role in the prevention and treatment of central nervous system (CNS) damage. This pathology is a serious problem in patients undergoing coronary artery bypass graft surgery (CABG) with extracorporeal circulation (ECC). Its biochemical diagnosis is mainly based on S100beta protein observations. This study aims to analyse different forms of Mg supplementation on serum S100beta concentrations in patients who have undergone CABG. PATIENTS AND METHODS: One hundred and twenty adult patients, who underwent CABG with extracorporeal circulation (ECC) with normovolemic haemodilution (NH) under general anaesthesia, were examined. According to the dose of Mg supplementation, patients were divided into six groups: A) patients receiving 3.33 mg of MgSO4 per min intravenously (i.v.), during surgery and the early postoperative period (18 hours); B) patients receiving oral Mg supplementation (OPS-Mg) and 3.33 mg of MgSO4 per min i.v., preoperatively; C) patients receiving 6.66 mg of MgSO4 per min i.v.; D) patients receiving OPS-Mg and 6.66 mg of MgSO4 per min i.v.; E) patients receiving 10 mg of MgSO4 per min i.v.; F) patients receiving OPS-Mg and 10 mg of MgSO4 per min i.v. Additionally, all patients were divided into three groups: O) patients, who did not receive dopamine or dobutamine infusion, DOP) those receiving dopamine infusion, and DOB) those receiving dobutamine infusion in doses dependent on their clinical state. Total serum Mg concentrations (Mg(t)) were measured at five time-points: 1) just before anaesthesia; 2) 10 min after ECC; 3) just after surgery, 4) in the morning of the first postoperative day, 5) in the morning of the second postoperative day. RESULTS: ECC resulted in S100beta elevation in all patients. In groups A, B and C, S100beta increased from the second to the fourth time-points; in groups D and F, S100beta increased at the second and third time-points; and in group E, S100beta increased only at the third time-point. The highest serum S100beta concentrations were noted in groups A and B, and the lowest concentrations were noted in groups E and F. There were significant correlations between serum S100beta and Mg(t) concentrations at time-point 3 in groups A, B, C and F. Moreover, there were significant overall correlations between S100beta and Mg in groups A and B. CONCLUSIONS: 1) ECC resulted in S100beta elevation, 2) infusion of 10 mg of MgSO4 per min reduced serum S100beta concentrations, and 3) dopamine infusion resulted in the highest serum S100beta concentrations.

Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

PURPOSE: Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. PATIENTS AND METHODS: Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. RESULTS: MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. CONCLUSION: SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

Prospective monitoring of adjuvant treatment in high-risk melanoma patients: lactate dehydrogenase and protein S-100B as indicators of relapse.

At present there is no international consensus on laboratory testing during the follow-up of melanoma patients. We carried out a prospective monitoring study on the usefulness of lactate dehydrogenase (LDH) and protein S-100B assessment in high-risk melanoma patients. Ninety-seven patients treated within prospective randomized trials on the adjuvant treatment of melanoma received quarterly clinical visits and blood examinations. During the median observation period of 30 months disease progression was observed in 52 of 97 patients (53.1%). The clinical course of melanoma was correlated to elevated LDH and S-100B serum concentrations. The comparative analysis revealed that (i) neither LDH nor S-100B were indicators of in-transit metastases, (ii) clinically apparent lymph nodes were rarely detected because of elevated S-100B (29.4%) or LDH (11.8%) only, and (iii) the S-100B assessment was superior to LDH in the identification of early distant metastasis (53.8 vs. 23.1%; P=0.008). The rate of false-positive (elevated) LDH-serum levels and S-100B-serum levels in clinically disease-free melanoma patients did not differ significantly (S-100B 1.9% vs. LDH 1.6%). Our data indicate that only protein S-100B might be used as a highly specific and relatively sensitive marker of early distant metastasis. Both markers, LDH and S-100B, are not able to identify loco-regional metastases with a low tumor load in high-risk melanoma patients.