Effects of Vitamin D3 in Long-Term Ovariectomized Rats Subjected to Chronic Unpredictable Mild Stress: BDNF, NT-3, and NT-4 Implications.

The purpose of this study was to explore the antidepressant-like effects of vitamin D3 at different doses (1.0, 2.5, and 5.0 mg/kg sc) on a model of depression produced by chronic unpredictable mild stress (CUMS) for 28 days in long-term (3 months) ovariectomized (OVX) adult rats. Sucrose preference (SPT), forced swimming (FST) and open-field (OFT) tests were conducted to examine the depression-like state. Serum corticosterone/adrenocorticotrophic hormone (ACTH) levels and hippocampal brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3/NT-4 expressions by ELISA kits and/or western blotting were determined to assess the possible mechanisms of the vitamin D3 effects on the depression-like profile in long-term OVX rats subjected to CUMS. The results showed that vitamin D3 (5.0 mg/kg), as well as fluoxetine treatment, considerably reversed the depression-like state in the SPT and FST, decreased serum corticosterone/ACTH levels, and increased BDNF and NT-3/NT-4 levels in the hippocampus of long-term OVX rats compared to OVX rats with CUMS (p < 0.05). Thus, a high dose of vitamin D3 (5.0 mg/kg sc) could improve the depression-like profile in long-term OVX adult female rats subjected to the CUMS procedure, which might be mediated by the regulation of BDNF and the NT-3/NT-4 signaling pathways in the hippocampus, as well as the corticosterone/ACTH levels of the blood serum.

The effect of Xinkeshu tablets on depression and anxiety symptoms in patients with coronary artery disease: Results from a double-blind, randomized, placebo-controlled study.

A large proportion of patients with coronary artery disease (CAD) suffer from depression or anxiety symptoms and this is associated with increased mortality [1]. This double-blinded, randomized, placebo-controlled, clinical trial (ChiCTR-IPR-17010940) aimed to explore whether Xinkeshu tablets can reduce anxiety or depressive symptoms in CAD patients and how this is related to the concentration of plasma cytokines. Sixty patients with CAD anda Hospital Anxiety and Depression Scale (HADS-a/HADS-d) score of ≥8 were treated with Xinkeshu tablets or placebo for 12 weeks following percutaneous revascularization. Depressive/anxiety symptoms and the levels of 440 peripheral blood cytokines were evaluated at baseline and after 12 weeks treatment. Results showed significantly lower (P < 0.05) HADS-a/HADS-d and PHQ-9 scores in CAD patients treated with Xinkeshu tablets than in those who received placebo. These improvements were associated with changes in certain peripheral blood cytokines; most notably trappin-2, adiponectin, interleukin 1ß (IL-1ß), thrombopoietin, activated leukocyte cell adhesion molecule (ALCAM), neurotrophin-3 (NT-3), and transferrin. A significant correlation between anxiety/depression symptoms and trappin-2, NT-3, transferrin, and ALCAM (p < 0.05) were observed in an independent cohort of patients with CAD. These findings were in-keeping with the anti-depressive effects of Xinkeshu tablets. This trial demonstrates that Xinkeshu tablets can improve anxiety and depression symtoms effectively address in patients with coronary heart disease possibly through increasing the blood ratio of anti-inflammatory:pro-inflammatory cytokines.

Immunopotentiator Thymosin Alpha-1 Promotes Neurogenesis and Cognition in the Developing Mouse via a Systemic Th1 Bias.

In early life, the immune system plays an essential role in brain development. In our study, the immunopotentiator thymosin alpha-1 (Ta1) was peripherally administered to neonatal mice to explore whether the peripheral immunopotentiator affects neurodevelopment and cognition, and to further investigate the relevant mechanism. Compared with the control group, the Ta1 mice displayed better cognitive abilities in early life. The numbers of 5-bromodeoxyuridine (BrdU)+, nestin+, T-box transcription factor 2 (Tbr2)+, BrdU+/doublecortin (DCX)+, BrdU+/ionized calcium-binding adaptor molecule 1 (Iba1)+, and BrdU+/neuronal nuclei (NeuN)+ cells in the hippocampus were increased in the Ta1 group, accompanied by increased interleukin-4 (IL-4), interferon-gamma, brain-derived neurotrophic factor, nerve growth factor, and insulin-like growth factor-1 as well as decreased IL-6 and tumor necrosis factor-α. Furthermore, the Ta1-group showed a Th1-polarized immune response, and the neurotrophic factors were positively associated with the Th1/Th2 ratio. More importantly, administration of Ta1 blocked lipopolysaccharide-induced impairment of hippocampal neurogenesis in early life. These findings suggest that peripheral Ta1 contributes to neurogenesis and cognition probably through a systemic Th1 bias, as well as neuroprotection against LPS infection by Ta1.

The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture.

Chordae tendineae rupture process is associated with increased production of inflammatory and angiogenesis mediators in connective tissues, which contributes to chronic inflammation and pathogenesis of degenerative chordae. A few trace elements are known to possess antioxidant, anti-inflammatory, and antiangiogenic properties. Therefore, the aim of this study was to determine whether zinc, selenium, midkine (MK), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-BB (PDGF-BB), and reduced glutathione (GSH) levels are associated with inflammation and angiogenesis processes in the context of a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. Seventy-one subjects comprising 34 patients with mitral chordae tendineae rupture (MCTR) and 37 healthy controls diagnosed on the basis of their clinical profile and transthoracic echocardiography were included in this study. The levels of GSH, MK, selenium, and zinc were found to be lower in the patients group when compared to control group. There were no significant difference in plasma TNF-α, IL-1ß, IL-6, IL-8, VEGF-A, and PDGF-BB levels between two groups. There were positive significant correlations between MK and GSH, MK, and selenium levels in patients with MCTR. According to our data in which selenium, zinc, MK, and GSH decreased in MCTR patients, inflammatory response, oxidative stress, and trace element levels may contribute to etiopathogenesis of mitral regurgitation and/or ruptured chordae tendineae.

Prophylactic vitamin D supplementation in ovarian hyperstimulation syndrome: an animal study.

PURPOSE: To investigate the effect of vitamin D in ovarian hyperstimulation syndrome (OHSS). METHODS: In this animal study, 28 immature female Wistar rats were divided into four groups: group 1 (control); group 2 (ovarian stimulation); group 3 (OHSS group); group 4 (OHSS + vitamin D group). All groups were killed 48 h after hCG administration and were compared in terms of vascular permeability, ovarian weight, ovarian diameter, vascular endothelial growth factor (VEGF) expression (immunohistochemistry) in ovarian tissue and pigment epithelium-derived factor (PEDF) level in the serum (ELISA test) with the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: VEGF expression in the vitamin D group was similar to that in the OHSS group. However, the PEDF level was significantly higher in the vitamin D group (p = 0.013). CONCLUSIONS: Prophylactic vitamin D supplementation is not sufficiently effective in preventing OHSS. Vitamin D effectively increases PEDF, which has an opposing effect on VEGF, which plays a key role in OHSS. Thus, the protective effect of Vitamin D on OHSS should be investigated with a vitamin D deficient model in the study group.

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.

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.

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.

Prognostic significance of serum S100B protein in high-risk surgically resected melanoma patients participating in Intergroup Trial ECOG 1694.

PURPOSE: We evaluated adjuvant trial E1694 to more precisely define the prognostic significance of serum S100B in patients with high-risk resected melanoma. PATIENTS AND METHODS: Sera from 670 E1694 patients banked at baseline and three additional time points were tested for S100B protein using chemiluminescence. RESULTS: S100B testing results showed that the higher the S100B level is, the higher the risk of relapse and death, regardless of the cutoff value. Univariate analysis showed that baseline S100B > or = 0.15 microg/L is significantly correlated with overall survival (OS; P = .01). Multivariate analysis was performed adjusting for significant prognostic factors (ulceration and lymph node status) and treatment. Baseline S100B was a significant prognostic factor for survival (hazard ratio = 1.39; 95% CI, 1.01 to 1.92; P = .043). S100B values measured at later time points over 1 year were also demonstrated to be significant prognostic factors for relapse-free survival (RFS) and OS. Lower S100B values at baseline and during follow-up were associated with longer survival. A changing S100B from low at baseline to high on follow-up seemed to be associated with the worst RFS and OS. CONCLUSION: For patients with high-risk surgically resected melanoma, a high baseline or increasing serum S100B is an independent prognostic marker of risk for mortality that may allow us to refine the application of adjuvant therapy in the future.