S-100 Protein Concentration Research Articles

Сравнение динамики биомаркеров нейронспецифической енолазы и протеина S-100 у новорожденных с гипоксически-ишемической энцефалопатией в зависимости от времени начала проведения лечебной гипотермии (0–6 часов и 6–24 часа после родов)

Актуальность. Сегодня остается невыясненным соответствие абсолютных сывороточных концентраций нейронспецифической енолазы (NSE) и протеина S-100 степени тяжести и возможным последствиям гипоксически-ишемической энцефалопатии (ГИЭ), а также динамика этих показателей на протяжении острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Цель: исследовать динамику сывороточных показателей нейронспецифической енолазы и протеина S-100 у доношенных новорожденных в течение острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Материалы и методы. Проспективное одноцентровое когортное исследование 205 доношенных младенцев, которые в 2012–2017 гг. находились на лечении в отделении анестезиологии и интенсивной терапии для новорожденных с диагнозом «гипоксически-ишемическая энцефалопатия». Дети были стратифицированы по времени от рождения до поступления в отделение интенсивной терапии (ОАИТН). Были исследованы сывороточные концентрации нейронспецифической енолазы и протеина S-100 в 1, 3 и 5-й день лечения как в целом во всей когорте, так и в группах: 0–6 часов (группа 1, n = 56) и более 6 часов после рождения (группа 2, n = 149). Результаты. Динамика S-100 была существенной в течение 5 дней в обеих группах новорожденных (p < 0,001). Однако не было найдено достоверного различия в тенденции изменения концентрации протеина S-100 в течение первых 5 дней в обеих группах (р = 0,082). Также не было статистически значимой разницы между пациентами, поступившими в первые 6 часов и позже, относительно значения S-100 (р = 0,320) в течение всех пяти дней, за исключением первого дня при поступлении (р = 0,002). Не было найдено статистически значимой разницы уровня NSE в группах как в динамике от 1-го до 5-го дней (р = 0,217), так и относительно раннего (0–6 часов) или позднего (более 6 часов) поступления в ОАИТН (р = 0,845). Нет также достоверного различия концентрации NSE между группами (р = 0,719). Выводы. Отсутствие достоверного различия динамики уровня протеина S-100 и NSE у новорожденных до 6 часов и после от момента рождения свидетельствует о возможности начала проведения лечебной гипотермии более чем через 6 часов после родов, если по организационным причинам ее не успели начать раньше.

Predicting the prognosis for severe brain injury patients: short-latency somatosensory evoked potential combined with electroencephalogram reactivity

Objective: To explore the the effectiveness of using short-latency somatosensory evoked potential(SLSEP) combined with electroencephalogram(EEG) reactivity to predict the prognosis of severe brain injury(SBI) patients. Methods: Consecutive patients with SBI admitted in neurosurgery intensive care unit(NSICU) at Xiangya Hospital of Central South University from July 2018 to January 2019 were prospectively collected. SLSEP and EEG were recorded in these patients in NSICU within two weeks after injury onset. EEG reactivity(EEG-R) was tested during EEG signal stabilization. In addition, the concentrations of serum neuron-specific enolase (NSE) and S100 protein were also detected. All patients were evaluated with Glasgow Outcome Scale(GOS) during 12 months' follow-up. GOS grade 3 to 5 was defined as favorable group, and GOS grade 1 to 2 was defined as unfavorable group. The association of relevant predictors with patient's prognosis was assessed. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate each potential predictor. Results: Forty-three patients were included in the study, with 26 patients of favorable outcomes and 17 patients with unfavorable prognosis. Univariate analysis revealed that the Glasgow Coma Scale (GCS) score, the concentration of serum NSE, EEG-R, the amplitude of SLSEP were all associated with the prognosis after 12 months' follow-up. Moreover, the AUC for prediction of favorable prognosis by GCS, NSE, EEG-R, SLSEP was 0.661(95%CI: 0.493-0.829), 0.697(95%CI: 0.531-0.862), 0.718(95%CI: 0.557-0.879) and 0.758(95%CI: 0.609-0.907) respectively. However, there was no significant difference of age, gender, pupillary light reflex and S100 protein between the two groups. Furthermore, multiple logistic regression analysis showed that only SLSEP amplitude (OR=2.058, 95%CI: 0.867-4.888) and EEG-R(OR=3.748, 95%CI: 0.857-16.394) were independent predictors of favorable prognosis, and the prognostic model containing these two variables yielded an predictive performance with an AUC of 0.798. Conclusion: The higher amplitude of SLSEP and the existence of EEG-R are predictors of good prognosis in SBI patients, and the combined use of SLSEP and EEG-R in predicting the prognosis of SBI patients is more reliable.

Concentration patterns of antibacterial factors and immunoglobulin A antibody in foremilk fractions of healthy cows.

Antibacterial factors act as innate immune components, which respond as soon as bacteria enter a living organism. To prevent and treat mastitis in cattle, understanding the concentrations of these substances inside the udder is important; however, they remain to be studied. In this investigation, the concentration of lingual antimicrobial peptide (LAP), S100 protein (S100A7), lactoferrin (LF), and immunoglobulin antibody were measured in the different fractions of foremilk. Lactating Holstein cows were examined, and 10 foremilk fractions were obtained from sequential samples up to 150 ml. The LAP concentrations in milk samples increased until 25 ml. The LF concentrations increased up to the 10 ml fraction, then stabilized at low level after the 50 ml fraction. For S100A7, some fractions had significantly higher (p < .05) concentrations than the 5 or 10 ml fractions. The IgA antibody concentration increased up to the 5 ml fraction, then after 50 ml fraction showed relatively low concentrations. This investigation determined the concentration patterns of LAP, LF, S100A7, and IgA antibody secreted in milk inside the udders of healthy lactating cows as baseline data. These distinct concentration patterns might indicate various protective responses.

P40 S100A8/A9 and S100A12 may be biomarkers for juvenile-onset systemic lupus erythematosus

Abstract Background Juvenile-onset SLE (JSLE) is a systemic autoimmune disease affecting young people before the age of 17 years. Despite recent progress in understanding the pathogenesis of JSLE, it remains unclear. The lack of reliable biomarkers makes the assessment of disease activity and organ involvement challenging. A family of pro-inflammatory molecules known as S100 proteins have recently emerged as potential biomarkers for monitoring disease activity in an adult-onset SLE and various (auto-) inflammatory conditions. We investigated the usefulness of S100A8/A9 and S100A12 serum and urine levels as biomarkers for renal involvement and/or disease activity in JSLE. Methods Serum and urine from JSLE patients (n = 60), matched healthy controls (n = 53) and patients with IgA vasculitis (disease controls, n = 9) were collected. S100A8/A9 and S100A12 concentrations in serum and urine samples were quantified using the Meso Scale Discovery Immunoassay [serum; median ng/mL (I.Q.R), urine; median ng/mmol creatinine (I.Q.R)]. Furthermore, S100 protein concentrations in serum and urine were compared between groups and between JSLE patients with active (BILAG scores A, B, C) and inactive (BILAG scores D, E) renal disease. Potential effects of age, sex and global disease activity (SLEDAI scores) on S100 protein concentrations were tested. Results S100A8/A9 levels were significantly increased in the serum of JSLE patients [1577.80ng/mL (2313.97)] when compared to healthy controls [732.53 ng/mL (1003.47); p &lt; 0.001)] and patients with IgA vasculitis [531.23 ng/mL (824.50); p &lt; 0.05)]. This, however, was not reflected in patients’ urine samples. S100A12 concentrations were significantly increased in both the serum [41.12 ng/mL = (106.06); p &lt; 0.05] and urine [90.12ng/mmol creatinine (348.44); p &lt; 0.05] when compared to healthy controls [serum;17.75ng/mL(47.16), urine; 14.88ng/mmol creatinine (198.36)]. No differences were seen between S100A12 protein levels in serum or urine of JSLE patients when compared to patients with IgA vasculitis. No differences were observed between S100 protein concentrations in the serum or urine of patients with JSLE with active vs. inactive renal disease, between ages or sexes. Also, global disease activity (SLEDAI) did not correlate with serum or urine S100 protein concentrations. Conclusion JSLE patients exhibit increased concentrations of S100A8/A9 and S100A12 proteins in the serum, independent of clinical disease activity. Furthermore, increased urine concentrations of S100A12 in JSLE patients are independent of current renal involvement or activity. Based on the small molecular weight of S100 proteins, this may suggest renal loss of elevated serum S100A12 (21 kDa) through the kidneys rather than being the result of kidney inflammation or damage. Thus, S100 proteins may help to distinguish JSLE patients from healthy controls and patients with the differential diagnosis IgA vasculitis, supporting previous reports in adult-onset SLE. Longitudinal assessment of S100 proteins for an individual patient and/or in combination with other biomarkers may be helpful in assessing disease activity in JSLE patients. Conflicts of Interest The authors declare no conflicts of interest.

Vitamin D and neurospecific proteins in children with inflammatory demyelinating diseases of central nervous system

The relevance of studying the provision of vitamin D in children with inflammatory diseases of the central nervous system (CNS) is due to a high prevalence of vitamin D deficiency conditions in children population, which, according to current literature data, leads to the imbalance of the immune system and a predisposition to a severe disease course, chronization of the process, development of autoimmune pathology. The study of the concentration of neurospecific proteins (NSP) in blood serum and cerebrospinal fluid (CSF) has been recently used to analyze the degree and nature of nervous tissue damage in case of various CNS diseases. The study included investigation of blood serum and CSF samples obtained from 107 children (34 – with encephalitis, 28 – with disseminated encephalomyelitis (DEM), 20 – with multiple sclerosis (MS), 25 – control group). Determination of vitamin D levels (25(OH)D) was performed by the method of electrochemiluminescence immunoassay, concentrations of myelin basic protein, neuron-specific enolase, S100 protein and glial fibrillary acidic protein – by ELISA method. A decrease in the concentration of vitamin D under 30 ng/ml was found in 95% of children with inflammatory diseases of the central nervous system, while the severity of the deficiency of 25(OH)D was associated with the severity of the disease course. In the early stages of the disease in all groups, a significant increase in the level of the main myelin protein was found, while an increase in the concentration of other NSP was observed less frequently and was associated with a severe and complicated course of the disease. Correlations of different intensity and direction between NSP and 25(OH)D were found, which indicates their importance in the pathogenesis of inflammatory diseases of CNS.

Value of NSE and S100 Protein of Kawasaki Disease with Aseptic Meningitis in Infant.

The cerebrospinal fluid content was examined for concentrations of S100 protein and neuron-specific enolase (NSE) in two diseases, Kawasaki disease (KD) with aseptic meningitis (1-3 months) and purulent meningitis (PM), to determine whether or not these measuremets could be used in early diagnosis. The content of cerebrospinal fluid S100 protein of KD with aseptic meningitis and PM were significantly higher than those in the control group. There was also a difference between KD and purulent meningitis (PM). The concentration of NSE was highest in the encephalitis group, which was statistically different from control group. However, there was no difference between the KD and control groups. The levels of S100 protein and NSE of KD with aseptic meningitis were lower than those in PM, indicating that the extent of neuronal damage is significantly lower than of the enchephalitis group. The area under the curve (AUCs) of the receiver operating characteristic (ROC) curve for S100 and NSE were both 0.972. The S100 threshold was 0.4315, the sensitivity was 92.1%, and the specificity was 100%, while the NSE threshold was 9.325, sensitivity 92.1%, and specificity 90%. The combined detection of NSE and S100 levels in the cerebrospinal fluid can be used for the differential diagnosis of KD with aseptic meningitis and purulent meningitis.

Can low cerebrospinal fluid S-100 protein concentration indicate the presence of unruptured intracranial aneurysm? – A preliminary study

Can low cerebrospinal fluid S-100 protein concentration indicate the presence of unruptured intracranial aneurysm? – A preliminary study

Pharmacological neuroprotection for intracerebral hemorrhages in patients with polyvascular disease

To evaluate the efficacy of pharmacological neuroprotection with protein, peptide and metabolic drugs as a part of basic intensive therapy for intracerebral hemorrhages in patients with polyvascular disease (PolyVD). Twenty-eight male patients with PolyVD referred to surgical treatment of intracerebral hemorrhages, who were on mechanical ventilation and received basic intensive care, were included in a single center prospective observational study. All patients were assigned either to routine daily i/v infusions of 10 ml cytoflavin in 0.9% sodium chloride solution for 10 days (n=12) or 0,2 mg daily of cellex subcutaneously (n=16). Central hemodynamics, intracranial pressure, and continuous indicators of the linear velocity of blood circulation were assessed. All patients underwent SOFA scoring. The markers of brain damage, including protein S-100-β (ng/l), antioxidant enzyme activity of superoxide dismutase (SOD) U/gr/Hb), glutathione peroxidase (U/gr/Hb) in the systemic circulation and jugular vein on the lesion side were determined. The length of stay in the intensive care unit and the number of nights were calculated. Mortality was assessed in both groups. Intracranial hypertension in both groups tended to subnormal parameters by 3-5 days. Vasospasm was reduced more rapidly (by the 3rd day) in the cytoflavin group compared to the cellex group (174 [152; 189] vs. 205 [182; 219], respectively). The latter demonstrated the less extent of cerebral damage according to S100 protein concentration. A comparative analysis showed that the antioxidant activity was significantly higher in the cytoflavin group. The cellex group demonstrated a pronounced trend towards the regression of neurological deficit on the NIHSS (p=0,025). The number of fatal outcomes and nights spent in the ICU were similar in both groups. The in-hospital stay was insignificantly shorter in the cellex group. It is recommended to add both antioxidant and neuropeptide pharmacological neuroprotectors in the routine intensive therapy for treating intracerebral hematomas in patients with PolyVD after surgical management.

Targeting low- or high-normal Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation: study protocol for a randomized pilot trial

BackgroundArterial carbon dioxide tension (PaCO2), oxygen tension (PaO2), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists.MethodsThe Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 23 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO2, PaO2, and MAP target levels for 36 h after admission.The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest.DiscussionThe trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low- or high-normal PaCO2, PaO2, and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified.Trial registrationClinicalTrials.gov, NCT02698917. Registered on 26 January 2016.

P 229 - Ubiquinol supplemenetation in elderly patients undergoing aortic valve replacement: Biochemical and clinical effects

There is a steady rise in the mean age of patients affected by heart disease undergoing cardiac surgery. However senescent myocardium has reduced tolerance to ischemic stress and there are clear indications about age-associated deficit in myocardial performance after operatory stress. CoQ10 improve several conditions related to bioenergetic deficit or increased exposure to oxidative stress. The use of ubiquinol, the reduced form of CoQ10, is promising in these clinical settings, on the basis of its superior bioavailability and of the alleged impaired CoQ10-reducing capacity in the elderly. In this study clinical and biochemical effects of ubiquinol were evaluated in 46 patients undergoing aortic valve replacement. They, affected by severe aortic stenosis, were randomized into 2 groups, placebo and CoQ10 group supplemented with 400 mg/die of ubiquinol starting, 7 days before surgery and continuing for 1 month after cardiac intervention. CoQ10 levels, its oxidative status and IL-6, TNF-alpha and S100 protein concentration in plasma were assessed. Moreover, main cardiac adverse effects in the postoperatory phase, NYHA class, contractility and myocardial hypertrophy were evaluated. Ubiquinol treatment improve basal (before surgery) oxidative status of CoQ10 and considerably mitigate increased oxidation related to the operation.

Immunization With a Pneumococcal Polysaccharide Vaccine in Children With Juvenile Idiopathic Arthritis Without Systemic Manifestations: a Prospective Study

Background . Patients with juvenile idiopathic arthritis (JIA) have an increased risk of being infected. Approximately half of all serious infections in children with JIA are associated with airway involvement. Objective . Our aim was to study the efficacy and safety of the pneumococcal 13-valent conjugate vaccine (PCV) in children with JIA. Methods. In a prospective cohort study, 5 groups were formed: children with JIA in the remission phase on methotrexate therapy (group 1) or etanercept (group 2), with JIA in the active phase prior to the appointment of methotrexate (group 3) or etanercept (group 4), control group (conditionally healthy children). 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment of methotrexate or etanercept in patients in the active phase. The main study outcome was the proportion of patients with a protective ( 40 mg/L) level of specific anti-pneumococcal antibodies (anti-SPP) IgG to Streptococcus pneumoniae 4 weeks after vaccination. In addition, we assessed the incidence of infectious events before and after vaccination as well as changes in the content of a high-sensitivity C-reactive protein, S100 protein, and post-vaccination period. Results. The study included 125 children. Four weeks after vaccination, the protective level of anti-SPP IgG was established in 21 (84%) patients in the 1st, 23 (92%) in the 2nd, 22 (88%) in the 3rd, 24 (96%) in the 4th and 5th groups (p =1.0). Increase in the concentration of S100 protein and high-sensitivity C-reactive protein after vaccination was not noted. JIA exacerbation episodes were not recorded in any patient. After immunization, the total number of infectious events decreased in all observed groups (p 0.001). Serious adverse events were not registered during the study. Conclusion . Vaccination with the 13-valent PCV in children with JIA is highly effective and is not accompanied by the development of serious adverse events.

The markers of damage of neurons and glia in cerebrospinal liquor under meningitis in children.

The actuality of analysis of cerebrospinal fluid under meningitis in children is conditioned by severity of course of disease with development of residual aftermaths in part of patients. The appearance of proteins specific for neurons, astro- and oligodendroglia in liquor and blood serum can serve as a marker of severity of damage of cerebral parenchyma and as a predictor of development of neurological deficiency. The analysis was applied to samples of liquor obtained during diagnostic lumbar puncture in 44 children (33 with viral serous meningitis, 11 with bacterial purulent meningitis). The detection of protein S-100, glial fibrillar acid protein and and neuron-specific enolase was implemented using solid-phase immune enzyme technique. The maximal increasing of concentrations of protein S-100 and glial fibrillar acid protein was detected at initial stage of bacterial purulent meningitis with consequent decreasing of at the stage of re-convalescence. Under serous meningitis at acute stage maximal high proved to be average value of concentration of neuron-specific enolase with tendency to its increasing at the stage of re-convalescence. The multi-directional correlation relationships are established concerning levels of of neuron-specific enolase, glial fibrillar acid protein and protein S-100 with standard liquorologic indices and their direct mutual relationships. The variability of levels of neuron-specific proteins in liquor is established associated with clinical characteristics of course of meningitis in children that testifies possibility of their application for specifying involvement into pathological process of different brain structures and necessity of further studying of relationship of infection affection of brain with development of neurological aftermaths at the residual period.

Clinical significance of BRAF mutation status in circulating tumor DNA of metastatic melanoma patients at baseline.

Circulating tumor DNA is a promising non-invasive tool for cancer monitoring. The main objective of our work was to investigate the relationship between mutant BRAF DNA in plasma and clinical response. Thirty-eight stage IV patients with a V600 mutated BRAF melanoma were included prior to any treatment. DNA was extracted from plasma and mutant DNA was detected using the amplification-refractory mutation system method. Before the beginning of any treatment, the corresponding BRAF mutation was detected in 29 of the 38 tested plasma samples (76.3% positive per cent agreement). We observed a strong correlation between the presence of circulating mutated DNA and overall survival (OS; P=.02), and with the number of metastatic sites (P=.01). The presence of circulating mutated DNA was also strongly correlated with serum LDH activity (P<.01) and S100 protein concentration (P<.01). Finally, seven patients presented discordant BRAF status in different tumor sites. In all these patients, the test performed on ctDNA was positive, suggesting that ctDNA analysis might be less sensitive to tumor heterogeneity. Altogether, these results suggest that plasmatic mutant BRAF DNA is a prognostic factor of OS, correlated with tumor burden. In addition, it represents an interesting alternative source of DNA to detect BRAF mutations before treatment.

The prognostic value of cerebral oxygenation and retrograde pressure during carotid endarterectomy

&lt;p&gt;&lt;strong&gt;Aim:&lt;/strong&gt; The study aimed to determine the predictive value of retrograde pressure (RP) indicators and cerebral oxygenation in the evaluation of ischemic brain damage during carotid endarterectomy (CEA).&lt;br /&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This nonrandomized, prospective pilot study included 87 patients with asymptomatic stenosis greater than 70% who underwent carotid endarterectomy under general anesthesia. Brain tolerance to ischemia was determined by measuring and evaluating RP (∆rSO2) and cerebral oxygenation (rSO2) during a trial clamping of the carotid artery. Depending on the degree of reduction of cerebral oxygenation from the baseline (∆rSO2) during a trial clamping of the carotid artery, patients were divided into 3 groups: the first group (n = 35) - ∆rSO2 &amp;lt;9.9%, the second group (n = 35) - ∆rSO2 from 10 to 19.9%, the third group (n = 14) - ∆rSO2 ≥ 20%. The primary end-point of the study was to obtain the AUC value exceeding 0.70, which could mean a high predictive quality of research methods. &lt;br /&gt;&lt;strong&gt;Results:&lt;/strong&gt; There were no perioperative strokes or myocardial infarctions during the study. Average time of carotid artery clamping was 28 (26-30) minutes. 3 patients who received temporary shunts were excluded from the study because of a simultaneous decrease in the rSO2 and ∆rSO2 indicators. It was found out that S-100 and NSE protein concentration in all groups did not significantly differ at different stages (p&amp;gt; 0.05). A temporary shutdown of blood flow in the carotid artery during CEA is accompanied by significant elevation of cerebral damage markers (S100, NSE) concentration with their subsequent restoration at 3 days after surgery. ROC - analysis revealed that none of the methods for assessing cerebral ischemic tolerance (RP, ∆rSO2 and rSO2) is precise enough (AUC &amp;gt; 0.7) to predict brain injury during carotid endarterectomy. Satisfactory, but a poor quality (AUC&amp;lt; 0.7) of predicting an increase in the reference values of S-100 protein neuromarkers was demonstrated by retrograde pressure, while the other indicators (∆rSO2 and rSO2) did not exceed the area under the curve (AUC) over 0.60. &lt;br /&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Methods of measuring retrograde pressure and cerebral oxygenation are merely a reflection of the collateral blood flow and the cerebral oxygenation level due to their close relationship, but they cannot be used as predictors of ischemic neuronal damage during carotid endarterectomy because of poor predictive quality.&lt;/p&gt;

ALA-induced photodynamic effect on viability, apoptosis and secretion of S100 protein, secreted by colon cancer cells in vitro

BackgroundS100 protein is a proven prognostic factor in cancers. In colorectal cancers, its secretion correlates with clinical stage of the disease. Photodynamic therapy (PDT) is used as a supporting therapy in treatment of this particular cancer. The main aim of our study was to estimate the effect of photodynamic therapy with 5-aminolevulinic acid (ALA) in sublethal doses (ALA-PDT) on the secretion of S100 protein by colon cancer cells. MethodsInvestigations were performed on two colon cancer cell lines. The SW480 cell line is a culture containing locally malignant cancer. The SW620 line is characterized by high metastatic activity. Each line was exposed to different concentrations of photosensitizer's precursor-ALA, and various level of light radiation. Afterwards, cell viability, using MTT and LDH assays and apoptosis of both lines was assessed. Then measurement of S100 protein concentration was performed using a 2-step enzyme immunoassay. ResultsAfter application of ALA PDT the S100 protein concentration was reduced by 27% in SW480 cell line and by 30% in SW620 cell line. At the same time there has been no increase in the concentration of S100 protein in cells exposed to the light alone. It was demonstrated that the more aggressive line SW620 releases higher levels of S100 proteins in comparison with the line SW480. ConclusionThe outcome of this study presented beneficial effect of ALA-PDT on persistent colon cancer cells. This therapy leads to decrease of S100 protein concentration in both colon cancer cell lines: SW480 and SW620.

Prognostic Serum Factors in Patients With Traumatic Brain Injury

Objective: The aim of the study was to systematically review which factor of serum, assessed in traumatic brain injury (TBI), predicts patient’s outcome. Materials and Methods: Databases were searched for relevant publications between 2005 and January 2013, and those fulfilling the following selection criteria were included: (1) studies conducted from 2005 until February 2013; (2) studies in which factors affecting the outcome after TBI were evaluated; (3) studies that defined TBI as “acute changes in brain function resulting in a strong external force to the head”; (4) studies in which the result was measured by the Glasgow Outcome Score (GCS) or by means of a comparable measure describing the activity limitation and neurological state; (5) studies in which the correlation between the measured factors in the first month after injury and prognosis was addressed; and (6) studies involving patients with moderate and/or severe TBI (GCS<13). All of the papers shortlisted were checked and approved by a specialist and expert in that field. A systematic review and analysis was performed for the prognostic factors assessed in the studies. Results: A total of 71 studies were included, 58 of which were of high quality. Most studies used the GCS at 6 months after injury as the outcome measure, sometimes in combination with other outcome measures. Strong evidence for predicting outcome was found for serum concentration of S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D-dimer, HSP 70, serum levels of IL-8, number of circulating endothelial progenitor cells (EPCs), and DNA levels in serum. Moderate evidence for predicting outcome was found for high serum MMP9. Strong evidence of no association was found for WBC count and serum cortisol levels, and moderate evidence of no association was found for serum total cholesterol. For other determinants, inconclusive or no evidence or limited evidence was found. Conclusions: S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D-dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum predicted outcome after TBI. WBC count, serum cortisol levels, total cholesterol, and MMP9 did not have predictive values.

Effect of recombinant human erythropoietin on brain injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass

Objective To evaluate the effect of recombinant human erythropoietin (rHuEPO) on brain injury in the patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB). Methods Forty-five patients with chronic valvular heart disease, aged 36-62 yr, weighing 42-92 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association of Ⅱ or Ⅲ, undergoing cardiac valve replacement with CPB, were randomly divided into 3 groups (n=15 each) using a random number table: control group (group C), and different doses of rHuEPO groups (EPO1 group, EPO2 group). In EPO1 and EPO2 groups, rHuEPO 40 and 80 IU/kg were injected intravenously before anesthesia induction, respectively.Before anesthesia induction (T0, baseline value), immediately after endotracheal intubation (T1), immediately after aortic cannulation (T2), immediately after cannulation of superior and inferior vena cava (T3), immediately after the beginning of CPB (T4), when each index was decreased to the minimal value during CPB (T5), after rewarming to 36.5 ℃ (T6), immediately after termination of CPB (T7), and at 1 h after termination of CPB (T8), regional cerebral oxygen saturation (rSO2), tissue hemoglobin index (THI), and changes in concentrations of oxyhemoglobin(△O2Hb), deoxyhemoglobin (△HHb) and total hemoglobin (△cHb) in bilateral frontal lobes were recorded.The patients whose minimal rSO2 ≤50% and decrease in minimal rSO2 ≥20% of the baseline value (△rSO2) were recorded.At T0, T8 and 2 h after termination of CPB (T9), venous blood samples were taken for determination of serum concentrations of S100 protein and neuron-specific enolase (NSE) by ELISA.At 1 day before surgery and 8 days after surgery, the patient's cognitive function was assessed using Mini-Mental State Examination, the Digit Span subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Digit Symbol subtest of the WAIS-R, the Trailing Making Test (Part A) and the Stroop Color Word Interference Test, while depression and anxiety were assessed by Zung Self-Rating Depression Scale and Zung Self-Rating Anxiety Scale, respectively.The occurrence of postoperative cognitive dysfunction was recorded. Results There was no significant difference among the three groups in bilateral rSO2 and △cHb, incidence of bilateral rSO2 ≤50% and postoperative cognitive dysfunction, Zung Self-Rating Depression Scale score, and Zung Self-Rating anxiety Scale score at each time point (P>0.05). Compared with group C, the incidence of left △rSO2≥20% was significantly decreased, the right △O2Hb was increased at T6, 8, the serum NSE concentrations were decreased at T9, the serum S100 protein concentrations were decreased at T8, and the number of the Digit Symbol subtest of the WAIS-R completed was increased in group EPO1, and right THI was significantly decreased at T2, T3, T5, T7 and T8, right △HHb was increased at T2 and T3, and the completion time of Stroop color word interference test B was shortened at 8 days after surgery in group EPO2 (P<0.05 or 0.01). Compared with group EPO1, the incidence of left △rSO2≥20% was significantly increased, the right THI was decreased at T2-4 and T6-8, and the left △O2Hb at T6-7 and right △O2Hb at T8 were decreased in group EPO2 (P<0.05). Conclusion rHuEPO 40 IU/kg injected intravenously before induction of anesthesia can mitigate brain injury in the patients undergoing cardiac valve replacement with CPB. Key words: Erythropoietin, recombinant; Brain injuries; Cardiopulmonary bypass; Heart valve prosthesis implantation

Utility of serum concentration of protein S100 at admission to the medical intensive care unit in prediction of permanent neurological injury.

IntroductionAdmission to the intensive care unit (ICU) may be preceded by dramatic events leading to permanent neurological injury. Plasma S100 protein levels are proved to be clinically useful in predicting neurological outcome following cardiac arrest. It is unclear, however, whether this may be extrapolated to a broader population of ICU patients.AimTo assess the utility of plasma S100 protein in predicting death, permanent neurological damage, or unfavourable outcome at admission to the intensive care unit.Material and methodsThe concentration of plasma S100 protein was established in 102 patients on admission to the ICU, regardless of their neurological status and the reason for admission. The majority of patients were admitted with various cardiac diseases, excluding trauma patients. The patients were classified into three groups with the following binary outcomes: permanent neurological deficit or restoration of consciousness; unfavourable outcome (death or survival with permanent neurological deficit) or favourable outcome; and death or survival.ResultsPlasma S100 protein levels at admission facilitated the identification of patients who later developed a permanent neurological deficit or regained consciousness (p < 0.0001). All patients with plasma S100 protein over 0.532 μg/l at ICU admission either developed a permanent neurological deficit or had an unfavourable outcome (death or survival with permanent neurological deficit). However, sensitivity for this cut-off value was only 48% and 40%, respectively.ConclusionsPlasma S100 protein levels over 0.532 μg/l are specific but not sensitive for both permanent neurological deficit and unfavourable outcome when assessed in a heterogeneous population at admission to the ICU.

Elevation of serum S100 protein concentration as a marker of ischemic brain damage in extremely preterm infants

BackgroundPeriventricular leukomalacia (PVL) is serious ischemic brain damage that occurs in extreme preterm infants. It is traditionally diagnosed by cranial echography. The purpose of this study was to investigate the relationship between serum S100 calcium-binding protein B (S100B) concentrations and ischemic brain damage, and to find the cutoff value for the early identification of ischemic brain damage in high-risk preterm infants. MethodsAt the age of 3 days, 7 days, 14 days, and 21 days, and before discharge, 22 extremely premature infants (i.e., gestational age <33 weeks) underwent blood sampling to determine the S100B concentrations and cranial echography examinations. The severity of ischemic brain damage in echographic images was scored on a scale of 0–11, and was recorded as the brain echography index (BEI). If the last BEI value was ≥7, the enrolled infants were grouped in the brain damage group. ResultsEight infants were assigned to the brain damage group and 14 infants were assigned to the no brain damage group. At each age point of the blood samplings, the serum S100B concentrations were significantly higher in the brain damage group than in the no brain damage group. There was a significantly positive correlation between the serum S100B concentrations and the BEI on the same day (r = 0.738, p < 0.001) and 7 days later (r = 0.774, p < 0.001). The receiver operating characteristic curve for the serum S100B concentrations showed that the area under curve was 0.985 (p < 0.001). The cutoff value of serum S100B of 1.0 μg/L had a sensitivity of 93.8% and specificity of 90.5% for the diagnosis of ischemic brain damage. ConclusionAn elevation in the serum S100B concentration is highly associated with ischemic brain damage in extreme preterm infants. Ischemic brain damage in a high-risk preterm infant is strongly suggested if the early serum S100B concentration is > 1.0 μg/L.

Prognostic Serum Factors in Traumatic Brian Injury: A Systematic Review

Background & Aim: Traumatic brain injury is one of the main causes of death and disability. The aim of this study is to systematically review the articles which assessed some serum factors of traumatic brain injury patients in relation to their outcomes.METHODS & Materials/Patients: Databases were searched for relevant publications from 2005 to 2014. Selection criteria were:Studies which evaluate the factors affecting the outcome after TBI, TBI defined as acute changes in brain function resulting in a strong external force to the head. Results were measured by Glasgow Outcome Score or a comparable measure.Factors were measured in first month after injury and the prognosis was addressed. All papers were checked and approved by a specialist and expert in that field. A systematic review was performed for prognostic factors.RESULTS: Sixty-three studies were included. Most studies used Glasgow Outcome Score at 6 months post-injury as outcome measure, sometimes in combination with other outcome measures. Strong evidence for predicting outcome was found for serum concentration of S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, partial thromboplastin time, platelet count, D.dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum. Moderate evidence for predicting outcome was found for high serum MMP9. Strong evidence of no association was found for WBC count and serum cortisol levels. Moderate evidence of no association was found for serum total cholesterol for other determinants, inconclusive or no evidence or limited evidence was found.CONCLUSION: S100 protein, NSE, MBP, NF-H, GFAP, UCH-L1, blood glucose levels, serum levels of LDH, sodium level, prothrombin time, Partial thromboplastin time, platelet count, D.dimer, HSP 70, serum levels of IL-8, number of circulating EPCs, and DNA levels in serum predicted outcome after traumatic brain injury. WBC count, serum cortisol levels, total cholesterol and MMP9 did not have predictive value. Language: en