S100B
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OBJECTIVES: To determine the prognostic potential of S100B protein in patients with craniocerebral injury, correlation between S100B protein and time, selected internal diseases, body habitus, polytrauma, and season. METHODS: We examined the levels of S100B protein in 124 patients with traumatic brain injury (TBI). RESULTS: The S100B protein level 72 h after injury and changes over 72 h afterwards are statistically significant for prediction of a good clinical condition 1 month after injury. The highest sensitivity (81.4%) and specificity (83.3%) for the S100B protein value after 72 h was obtained for a cut-off value of 0.114. For the change after 72 h, that is a decrease in S100B value, the optimal cut-off is 0.730, where the sum of specificity (76.3%) and sensitivity (54.2%) is the highest, or a decrease by 0.526 at the cut-off value, where sensitivity (62.5%) and specificity (62.9%) are more balanced. The S100B values were the highest at baseline; S100B value taken 72 h after trauma negatively correlated with GCS upon discharge or transfer (r=-0.517, P<0.0001). We found no relationship between S100B protein and hypertension, diabetes mellitus, BMI, or season when the trauma occurred. Changes in values and a higher level of S100B protein were demonstrated in polytraumas with a median of 1.070 (0.042; 8.780) μg/L compared to isolated TBI with a median of 0.421 (0.042; 11.230) μg/L. CONCLUSION: S100B protein level with specimen collection 72 h after trauma can be used as a complementary marker of patient prognosis.
- MeSH
- biologické markery * krev MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- S-100 kalcium vázající protein G, podjednotka beta * krev MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- traumatické poranění mozku * krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * genetika krev MeSH
- melanom * genetika krev patologie diagnóza chirurgie MeSH
- mutace * MeSH
- nádorové biomarkery * krev genetika MeSH
- nádory kůže * krev genetika patologie diagnóza chirurgie MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- protoonkogenní proteiny B-Raf * genetika krev MeSH
- S-100 kalcium vázající protein G, podjednotka beta * krev genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- tekutá biopsie metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Brain injury is a multifaceted condition arising from nonspecific damage to nervous tissue. The resulting cognitive developmental impairments reverberate through patients' lives, affecting their families, and even the broader economic landscape. The significance of early brain injury detection lies in its potential to stave off severe consequences and enhance the effectiveness of tailored therapeutic interventions. While established methods like neuroimaging and neurophysiology serve as valuable diagnostic tools, their demanding nature restricts their accessibility, particularly in scenarios such as small hospitals, nocturnal or weekend shifts, and cases involving unstable patients. Hence, there is a pressing need for more accessible and efficient diagnostic avenues. Among the spectrum of brain injuries, hypoxic-ischemic encephalopathy stands out as a predominant affliction in the pediatric population. Diagnosing brain injuries in newborns presents challenges due to the subjective nature of assessments like Apgar scores and the inherent uncertainty in neurological examinations. In this context, methods like magnetic resonance and ultrasound hold recommendations for more accurate diagnosis. Recognizing the potential of serum biomarkers derived from blood samples, this paper underscores their promise as a more expedient and resource-efficient means of assessing brain injuries. The review compiles current insights into serum biomarkers, drawing from experiments conducted on animal models as well as human brain pathologies. The authors aim to elucidate specific characteristics, temporal profiles, and the available corpus of experimental and clinical data for serum biomarkers specific to brain injuries. These include neuron-specific enolase (NSE), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), and high-mobility-group-protein-box-1 (HMGB1). This comprehensive endeavor contributes to advancing the understanding of brain injury diagnostics and potential avenues for therapeutic intervention.
Úvod: Traumatické poranění mozku (traumatic brain injury; TBI) je v rozvojových zemích stále velmi vážným problémem. Nevyhnutelným výsledkem traumatu je sekundární fáze s neuroinflamací, která vede ke zvýšené morbiditě a mortalitě. Do současné doby byly tetovány různé účinné látky a léčebné modality. První klinicky dostupný tryptan, který byl použit k léčbě migrény – sumatriptan (SUM) – byl předtím hodnocen při cerebrální, testikulární a renální ischemii, ale pokud je nám známo, toto je první článek, který hodnotí jeho protizánětlivé a antioxidační vlastnosti po experimentálním TBI u potkanů. Cíl: Při použití naší techniky experimentálního traumatu jsme si dali za cíl zjistit, zda SUM zlepšuje stav při zánětlivé fázi TBI, a to prostřednictvím neurologické, histologické a biochemické analýzy. Metodologie: Dvacet tři potkanů kmene Wistar albino bylo náhodně rozděleno do tří skupin: kontrolní skupina, skupina s traumatem a skupina s traumatem, které byl podáván SUM. U posledních dvou skupin bylo vyvoláno experimentální difuzní poranění kortexu, které simulovalo TBI. Subjekty podstoupily neurologické hodnocení prostřednictvím Garciova testu, histologické vyšetření pomocí nového skórovacího systému a biochemickou analýzu hladin neuron specifické enolázy (NSE), S100B, kaspázy-3 (CASP3) a tzv. „rat thiobarbituric acid reactive substances“ (TBARS). Výsledky: Skupina, které byl podáván SUM, měla lepší skóre Garciova testu (p < 0,001), zvýšený protizánětlivý účinek (p = 0,004) a neuroprotektivní účinek (p < 0,001) a zároveň sníženou hladinu TBARS (p < 0,05), ale v porovnání se skupinou s traumatem měly podobné hladiny S100B, CASP3 a NSE. Závěr: Podání SUM může přinést prospěch z hlediska snížení mortality a morbidity po TBI vlivem jeho protizánětlivého a antioxidačního účinku. Nový skórovací systém použitý v této studii může být u podobných experimentů užitečným nástrojem.
Introduction: Traumatic brain injury (TBI) continues to be a devastating problem in developing countries. The inevitable traumatic effect is followed by a secondary phase of neuroinflammation leading to increased morbidity and mortality. Numerous agents and treatment modalities have been tested to date. The first clinically available triptan used to treat migraine, sumatriptan (SUM), has been evaluated for cerebral, testicular and renal ischemia previously but to our knowledge this is the first paper where its anti-inflammatory and anti-oxidative effects after experimental TBI in rats has been evaluated. Aim: Employing an experimental trauma technique, we aimed to investigate whether SUM has ameliorating effects on the inflammatory phase of TBI via neurological, histological and biochemical analyses. Methodology: Twenty-three Wistar albino rats were randomly divided into three groups: control, trauma and trauma + SUM. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. The subjects underwent neurological assessment via the Garcia Test, histological analysis via a novel scoring system and biochemical analyses of neuron specific enolase (NSE), S-100B, caspase-3 (CASP3), and rat thiobarbituric acid reactive substances (TBARS) levels. Results: SUM receiving group had a better Garcia Test score (P < 0.001), higher anti-inflammatory score (P = 0.004) and higher neuroprotective score (P < 0.001) along with a better histopathological score when compared with the trauma group. SUM receiving group had lower levels of S100B, CASP3 and TBARS. SUM was unable to reduce NSE levels. Conclusion: SUM may prove to be beneficial in decreasing mortality and morbidity rates after TBI through its anti-inflammatory and anti-oxidative effects. The novel scoring system used in this study may be a valuable tool for similar experiments.
Extensive axonal and neuronal loss is the main cause of severe manifestations and poor outcomes in tick-borne encephalitis (TBE). Phosphorylated neurofilament heavy subunit (pNF-H) is an essential component of axons, and its detection in cerebrospinal fluid (CSF) or serum can indicate the degree of neuroaxonal damage. We examined the use of pNF-H as a biomarker of neuroaxonal injury in TBE. In 89 patients with acute TBE, we measured CSF levels of pNF-H and 3 other markers of brain injury (glial fibrillary acidic protein, S100B and ubiquitin C-terminal hydrolase L1) and compared the results to those for patients with meningitis of other aetiology and controls. Serum pNF-H levels were measured in 80 patients and compared with findings for 90 healthy blood donors. TBE patients had significantly (P<0.001) higher CSF pNF-H levels than controls as early as hospital admission. Serum pNF-H concentrations were significantly higher in samples from TBE patients collected at hospital discharge (P<0.0001) than in controls. TBE patients with the highest peak values of serum pNF-H, exceeding 10 000 pg ml-1, had a very severe disease course, with coma or tetraplegia. Patients requiring intensive care had significantly higher serum pNF-H levels than other TBE patients (P<0.01). Elevated serum pNF-H values were also observed in patients with incomplete recovery (P<0.05). Peak serum pNF-H levels correlated positively with the duration of hospitalization (P=0.005). Measurement of pNF-H levels in TBE patients might be useful for assessing disease severity and determining prognosis.
- MeSH
- biologické markery MeSH
- intermediární filamenta MeSH
- klíšťová encefalitida * diagnóza MeSH
- lidé MeSH
- prognóza MeSH
- progrese nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Rodents are the most commonly used animals in the study of spontaneous preterm delivery (PTD). Intra-amniotic inflammation/infection is a frequent and important cause of PTD. Intraperitoneal and intrauterine administrations of inflammatory agents are traditional methods to establish a rodent model of PTD associated with inflammation and infection. The intra-amniotic administration of inflammatory or infectious triggering agents to rodents can be useful to study not only intra-amniotic inflammatory response but also PTD associated with intra-amniotic inflammation/infection. OBJECTIVE: This systematic review aimed mainly to assess and analyze all described methods of intra-amniotic administration of infectious and/or inflammatory agents to create a rodent model of intra-amniotic inflammation associated with PTD. METHODS: A literature search through two electronic databases from their earliest entries to February 2019 was performed. The selection criteria were as follows: (1) rodents as model animals, (2) a model of intra-amniotic inflammation/infection associated with PTD, and (3) intra-amniotic administration of triggering agents. Data extraction included specification of the study (author and year of publication), characteristics of study animals (species, strain, and number of animals), characteristics of intervention (timing and used technique), substance used for induction of intra-amniotic inflammation/infection, and outcome assessment. RESULTS: The search identified a total of 4673 articles, of which 118 were selected for full-text reading, but only 13 studies were included in the review. Intra-amniotic administration was used only in the articles that were published beyond 2004. Two different approaches were identified: (1) open surgery with direct puncture of the amniotic sacs and (2) transabdominal ultrasound-guided puncture of the gestational sacs. Live microorganisms (Ureaplasma parvum), bacterial products (extracellular membrane vesicles), and pathogen-associated (lipopolysaccharide) and damage-associated molecular patterns (high mobility group box-1, S100B, and surfactant protein A) were used to simulate intra-amniotic inflammation/infection. Differences in the effect on intra-amniotic inflammation/infection associated with PTD in the mouse model were identified among triggering agents. Intra-amniotic application of lipopolysaccharide in the rat model caused intra-amniotic inflammation, but it did not lead to PTD. CONCLUSION: The intra-amniotic administration of the triggering agents can be used to study intra-amniotic inflammatory response and intra-amniotic inflammation/infection in the rodents model.
- MeSH
- chorioamnionitida * chemicky indukované farmakoterapie mikrobiologie MeSH
- gestační váček MeSH
- hlodavci MeSH
- krysa rodu rattus MeSH
- myši MeSH
- plodová voda mikrobiologie MeSH
- předčasný porod * MeSH
- zánět farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.
- Publikační typ
- časopisecké články MeSH
