S-100 Protein Levels Research Articles

The regenerative effect of exosomes isolated from mouse embryonic fibroblasts in mice created as a sciatic nerve crush injury model.

Exosomes (Exos) are candidates for functional recovery and regeneration following sciatic nerve crushed (SNC) injury due to their composition which can accelerate tissue regeneration. Therefore, mouse embryonic fibroblast-derived exosomes were evaluated for their regenerative capacity in SNC injury. In the study, 40Balb/c males (20 ± 5g) and two pregnant mice (for embryonic fibroblast tissue) were used and crushed injury was induced in the left sciatic nerve with an aneurysm clamp. Sciatic nerve model mice were randomly divided into 5 groups (n = 8; control, n = 8; sham, n = 8; SNC, n = 8; Mouse embryonic fibroblast exosome (mExo), n = 8; SNC + Mouse embryonic fibroblast exosome (SNC + mExo). Rotarod tests for motor functions and hot plate and von Frey tests for sensory functions were analyzed in the groups. Expression changes of exosome genes (RARRES1, NAGS, HOXA13, and MEIS1) immunohistochemical analysis of these gene proteins, and structural exosome NF-200 and S100 proteins were evaluated by confocal microscopy. Behavioral analyses showed that the damage in SNC was significant between groups on day14 and day28 (P < 0.05). In behavioral analyses, it was determined that motor functions and mechanical sensitivity lost in SNC were regained after mExo treatment. While expression of all genes was detected in MEF-derived exosomes, the high expression was MESI1 and the low expression was HOXA13. NF200, an indicator of axon number and neurofilament density, was found to decrease in SNC (P < 0.001) and increase after treatment, but not significantly. The decreased S100 protein levels in SNC and the increase detected after treatment were not significant. The expression of four mRNAs in mExos indicates that these genes may have an effect on regenerative processes after SNC injury. The regenerative process supported by tissue protein expressions demonstrates the therapeutic potential of mExo treatment.

Proinflammatory Microenvironment in Adenocarcinoma Tissue of Colorectal Carcinoma.

Cancer-promoting proinflammatory microenvironment influences colorectal cancer (CRC) development. We examined the biomarkers of inflammation, intestinal differentiation, and DNA activity correlated with the clinical parameters to observe progression and prognosis in the adenocarcinoma subtype of CRC. Their immunohistology, immunoblotting, and RT-PCR analyses were performed in the adenocarcinoma and neighboring healthy tissues of 64 patients with CRC after routine colorectal surgery. Proinflammatory nuclear factor kappa B (NFκB) signaling as well as interleukin 6 (IL-6) and S100 protein levels were upregulated in adenocarcinoma compared with nearby healthy colon tissue. In contrast to nitrotyrosine expression, the oxidative stress marker 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was increased in adenocarcinoma tissue. Biomarkers of intestinal differentiation β-catenin and mucin 2 (MUC2) were inversely regulated, with the former upregulated in adenocarcinoma tissue and positively correlated with tumor marker CA19-9. Downregulation of MUC2 expression correlated with the increased 2-year survival rate of patients with CRC. Proliferation-related mammalian target of rapamycin (mTOR) signaling was activated, and Ki67 frequency was three-fold augmented in positive correlation with metastasis and cancer stage, respectively. Conclusion: We demonstrated a parallel induction of oxidative stress and inflammation biomarkers in adenocarcinoma tissue that was not reflected in the neighboring healthy colon tissue of CRC. The expansiveness of colorectal adenocarcinoma was confirmed by irregular intestinal differentiation and elevated proliferation biomarkers, predominantly Ki67. The origin of the linked inflammatory factors was in adenocarcinoma tissue, with an accompanying systemic immune response.

(276) Light Emitting Diodes (LED) as a Potential Therapy for Erectile Function: A Preclinical Study in a Cavernous Nerve Injury Model

Abstract Introduction Erectile dysfunction (ED) induced by nerve injury including prostatectomy poorly responds to PDE5 inhibitor and requires invasive treatment. Light emitting diodes (LED) in some spectral range, is able to irradiate cells without overheating for its low energy consumption and to enhance mitochondrial metabolism, intracellular energy transfer, and thereby cell proliferation and tissue regeneration in some organs. We, herein, investigated whether and how LED therapy may improve penile erection in mouse cavernous nerve injury (CNI) - induced ED model Objective To identify the optimal LED parameters using molecular, histological, and erectile function analysis in cavernous nerve injury. Methods Eight week old male mice (n=120) were divided into 5 age-matched groups, a sham operation group receiving heat treatment, a CNI group receiving heat treatment, a CNI group receiving red light of LED (wavelength; 660 ±3% nm), a CNI group receiving near infrared light of LED (wavelength; 830 ±2% nm), and a CNI group receiving combination of both LED light. Mice were exposed to LED light for 30 minutes on the ventral side including penis for 5 consecutive days after CNI operation. Molecular study, histopathological analysis of the penis and erectile function test were done 2 weeks following the treatment in each subject. Results CNI group with heat treatment had much lower maximum and total ICP than sham control group. In contrast, three groups with LED light irradiation exhibited considerably improved maximum and total ICP, and the group with both LED treatments had the best erectile performance, reaching 90% of the sham surgery group. Histologically, mice treated with RED, NIR, or LED irradiation had more cavernous pericytes and endothelial cells than CNI mice after sham operation. In addition, all three CNI groups with various LED lengths improved neuroprotection and brain regeneration in CNI mice. All groups treated with LED showed increased expression of βIII-tubulin, neurofilament-1, and nNOS in cavernous tissue and dorsal nerve bundle. Additionally, LED treatment in three groups, particularly the combination group, significantly increased βIII-tubulin, S100, and myelin basic protein levels, indicating axonal integrity or expansion in the dorsal root and major pelvic ganglions. Molecular analysis of downstream signals of neural regeneration or angiogenesis showed that 3 groups with LED treatment increased phosphorylated PI3K, neurotrophic factors like BDNF, NGF, and NT-3, and angiogenic factors like angiopoietin1 and vascular endothelial growth factor in cavernous tissue and llpopolysaccharide-treated PC-12 cells. The TUNEL assay and BrdU staining of these tissue and cells showed lower cell apotosis and proliferation in LED-treated groups. Conclusions The results show that LED therapy with RED, NIR, preferably combination of each wavelength improves penile erection by neural progection or regeneration in cavernous nerve injury induced-ED. This noninvasive therapy may be useful in near future for ED refractory to PDE5 inhibitor. As far as we are aware, this is the first research to demonstrate the advantage of LED therapy, low level in sexual dyfunction field. Disclosure No.

Rehabilitation Exercises Supported by Monitor-Augmented Reality for Patients with High-Grade Glioma Undergoing Radiotherapy: Results of a Randomized Clinical Trial.

Exercise has been shown to improve quality of life (QoL) and even treatment outcomes in cancer patients. However, the evidence to support the benefits of exercise in patients with high-grade glioma (HGG) is limited. Therefore, we performed a randomized clinical trial (RCT) to examine the effect of augmented-reality-based rehabilitation exercises on physical and functional fitness, cognitive function, fatigue, mood, QoL, selected blood parameters, brain derived neurotrophic factor (BDNF), and S100 protein in patients with HGG. Adult patients with HGG scheduled to undergo radiotherapy after tumor resection were randomized to participate in an exercise program (experimental group, n = 25) or to receive usual care (controls, n = 22). Physical and mental fitness was measured at baseline, after the completion of radiotherapy, and at 3 months. The following tests were administered: Handgrip Strength Test; 6-Minute Walk Test; Time Up and Go test; Functional Independent Measure scale; Addenbrooke's Cognitive Examination III (ACE III); Hospital Anxiety and Depression Scale; Functional Cancer Therapy Assessment-Brain; and Functional Assessment of Chronic Illness Therapy-Fatigue. We also measured blood parameters, BDNF, and S100 protein levels. No significant changes were observed in the exercise group. However, the controls experienced a significant decrease in HGS and in the ACE III attention domain. No significant changes were observed in QoL, fatigue, BDNF, or S100 levels in either group. Augmented-reality-based exercise during radiation therapy may prevent loss of muscle strength and attention in patients with HGG.

Neuroinflammation as a Main Etiopathogenetic Factor in the Development of Drug-Resistant Epilepsies and Epileptic Encephalopathies

Background: despite the large number of newly emerging antiepileptic drugs, the frequency of treatment-resistant forms of epilepsy has not decreased, averaging 25–30%. Moreover the number of epileptic encephalopathies of early childhood has increased. One of the reasons of drug resistance is neuroinflammation. Aim: to evaluate the role of neuroinflammation in the pathogenesis of severe forms of childhood epilepsy and resistant adult epilepsy.Patients and methods: the main group 1 — 94 pediatric patients with epileptic encephalopathies, average age 20.4 ± 6.2 months. The control group 1 — 42 pediatric patients in remission of epilepsy, average age 21.3 ± 5.7 months. The main group 2 — 35 adult patients with resistant forms of epilepsy, average age 38.3 ± 7.9 years. The control group 2 — adult patients in remission of epilepsy 47 patients, average age 34.2 ± 8.6 years. The following blood levels were analyzed: neuron-specific enolase, S100 protein, eosinophilic cationic protein, IgE total level, total level of circulating immune complexes, leukocyte elastase and alpha-1 antitrypsin. Results: in the group of children with epileptic encephalopathies, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 27.6 ± 5.3 ng/ml compared to 14.2 ± 3.5 ng/ml in the control group. The average S100 protein level is 0.232 ± 0.041 ng/ml compared to 0.092 ± 0.024 ng/ml in the control group. The average level of eosinophilic cationic protein is 39.7 ± 9.4 ng/ml compared with 18.2 ± 5.3 ng/ml in the control group. The average IgE level is 157.3 ± 64.2 IU/ml compared to 42.2 ± 17.5 IU/ml in the control group. The average level of circulating immune complexes is 265.6 ± 54.4 UE/ml compared to 56.8 ± 16.8 UE/ml in the control group. In the group of adult patients with resistant forms of epilepsy, an increase in neuroinflammation indicators was revealed in most patients. The average level of neuron-specific enolase is 19.2 ± 7.2 ng/ml compared to 13.1 ± 4.1 ng/ml in the control group. The average S100 protein level is 0.115 ± 0.037 ng/ml compared to 0.093 ± 0.018 ng/ml in the control group. The average level of eosinophilic cationic protein is 24.2 ± 6.7 ng/ml compared to 18.8 ± 4.7 ng/ml in the control group. The average level of total IgE is 117.9 ± 32.6 IU/ml compared to 53.4 ± 18.2 IU/ml in the control group. The average level of circulating immune complexes is 235.2 ± 43.7 UE/ml compared to 62.6 ± 20.4 UE/ml in the control group. The level of leukocyte elastase was increased in 32 (91.4%) patients, the average level was 267.2 ± 36.8 nmol/min × ml compared with 175.2 ± 23.8 nmol/min × ml in the control group. The level of alpha-1 antitrypsin was increased in 33 (94.3%) patients, the average level was 55.2 ± 12.1 ng/ml compared with 26.4 ± 15.6 ng/ml in the control group. Conclusion: neuroinflammation is the factor of the development of severe forms of epilepsy and the formation of resistance in epileptic encephalopathies. Epileptic encephalopathies of early childhood according to their etiopathogenesis should be considered as subacute encephalitis, where seizures are only one sign of the pathological inflammatory process. The main clinical aim of the treatment of epileptic encephalopathies is the diagnosis of cumulative antigenic load and the selection of anti-inflammatory therapy.

Serum levels of S-100 protein are directly proportional to the size, number, thickness and degree of cellularity of congenital melanocytic nevi

Serum levels of S-100 protein are directly proportional to the size, number, thickness and degree of cellularity of congenital melanocytic nevi

Correlation Studies between S100 Protein Level and Soluble MIA or Tissue MelanA and gp100 (HMB45) Expression in Cutaneous Melanoma.

(1) Background: Cutaneous melanoma (CM) originates from melanocytes and causes 90% of skin cancer deaths; therefore, the comparison of different soluble and tissue markers could be valuable in the detection of melanoma progression and therapy monitoring. The present study is focused on the potential correlations between soluble S100B and MIA protein levels in different melanoma stages or with tissue expression of S100, gp100 (HMB45), and MelanA biomarkers. (2) Methods: Soluble S100B and MIA levels were evaluated by means of immunoassay methods in blood samples from 176 patients with CM, while tissue expressions of S100, MelanA, and gp100 (HMB45) were detected by means of immunohistochemistry in 76 melanomas. (3) Results: Soluble S100B correlated with MIA in stages III (r = 0.677, p < 0.001) and IV (r = 0.662, p < 0.001) but not in stages I and II; however, 22.22% and 31.98% of stage I and II patients, respectively, had high values for at least one of the two soluble markers. S100 tissue expression correlated with both MelanA (r = 0.610, p < 0.001) and HMB45 (r = 0.476, p < 0.01), while HMB45 and MelanA also significantly positively correlated (r = 0.623, p < 0.001). (4) Conclusions: Blood levels of S100B and MIA corroborated with melanoma tissue markers expression could help to improve the stratification process for patients with a high risk of tumor progression.

S100 as Serum Tumor Marker in Advanced Uveal Melanoma

S100 protein is routinely used as a serum tumor marker in advanced cutaneous melanoma. However, there is scarce and inconclusive evidence on its value in monitoring disease progression of uveal melanoma. In this monocenter study, we retrospectively assessed the connection between documented S100 protein levels of patients suffering from stage IV uveal melanoma and the clinical course of disease. Where available, we analyzed expression of S100 in melanoma metastases by immunohistochemistry. A total of 101 patients were included, 98 had available serum S100 levels, and in 83 cases, sufficient data were available to assess a potential link of S100 with the clinical course of the uveal melanoma. Only 12 of 58 (20.7%) patients had elevated serum levels at first diagnosis of stage IV disease. During progressive disease, 54% of patients showed rising serum S100 levels, while 46% of patients did not. Tumor material of 56 patients was stained for S100. Here, 26 (46.4%) showed expression, 19 (33.9%) weak expression, and 11 (19.6%) no expression of S100. Serum S100 levels rose invariably in all patients with strong expression throughout the course of disease, while patients without S100 expression in metastases never showed rising S100 levels. Thus, the value of S100 serum levels in monitoring disease progression can be predicted by immunohistochemistry of metastases. It is not a reliable marker for early detection of advanced disease.

Clinic and diagnosis of encephalopathy of critical conditions in children with infectious diseases

Purpose: to assess the functional state of the brain in critically ill encephalopathy in children with infectious diseases.Materials and methods: 75 patients aged from 1 month to 17 years 11 months with infectious diseases, who were in the intensive care unit of the clinic, were examined, divided into two groups: the main group and the comparison group. Exclusion criteria: patients with cerebral palsy, organic lesions of the central nervous system, neuroinfections and epilepsy. Conducted daily clinical and neurological examination; study of the level of neurospecific proteins (NSE, protein S100) in blood serum; electroencephalography; study of evoked potentials of various modalities; ultrasound examination of the optic nerves, neuroimaging.Results: All patients had general infectious manifestations, the development of sepsis syndrome, cerebral systemic disorders with impaired consciousness, as well as convulsive syndrome. In the acute period of the disease in the main group, NSE values in 87.5% of children were within the upper limit of normal, S100 protein levels were many times higher than those in the comparison group. In dynamics, all patients showed an increase in the level of NSE, which correlated with persistent neurological symptoms in the form of irritability, weakness, and cognitive decline. In the comparison group, an increase in NSE occurred in 53% of children, an increase in S100 - in 83%. By the time of discharge, 47% of patients had an increase NSE and S100 protein. Visual evoked potentials in 84% of the children of the main group in the acute period, had a decrease the amplitude of the N2-P2 cortical response was revealed without significant dynamics in the future, which was accompanied by pronounced clinical manifestations, which made it possible to substantiate the expediency of dispensary observation of children who underwent a critical condition against the background of severe infectious pathology.Conclusion: in infectious diseases in children that are not accompanied by inflammatory processes in the nervous system, but proceed with the development of a critical condition, there is a neuropsychiatric deficit in the outcomes, which necessitates follow-up follow-up of such patients in the future.

Regional Cerebral Oxygenation in Patients with Severe COVID-19

The aim of the study was to assess regional cerebral oxygenation (rScO₂) in patients with acute respiratory distress syndrome (ARDS) associated with COVID-19.Material and methods. The cross-sectional study was conducted. Twenty-eight patients with severe COVID-19 who were admitted in the intensive care unit were enrolled. Regional cerebral oxygenation was assessed using near-infrared spectroscopy, laboratory markers of cerebral damage, clinical and laboratory characteristics.Results. Median age of patients was 65 years, of whom 50% were men. Three (11%) patients had severeARDS, 8 (29%) patients had moderate ARDS, and 17 (60%) patients had mild ARDS. Mechanical ventilation was performed in 20 (71%) patients, vasopressors were used in 14 (50%) patients. The median levels of cerebral saturation were normal and did not differ between the left (rScO₂l) and right (rScO₂r) hemispheres (68 (58–75) and 69 (59–76), respectively). The level of S-100 protein was increased (0.133 (0.061–0.318) µg/l) in contrast to the normal level of neuron-specific enolase (12.5 (8.0–16.5) µg/l). A correlation was found only between rScO₂ and hemoglobin level (rho=0.437, P=0.02) and between rScO₂ and lymphocyte count (rho=–0.449, P=0.016). An increase in S-100 negatively correlated with a decrease in Glasgow Coma Scale score (rho=–0.478, P=0.028).Conclusion. Near-infrared spectroscopy did not reveal a decrease in rScO₂ among patients with ARDS associated with COVID-19. The S-100 protein is a useful marker for the assessment of impaired consciousness. Further study of the causes of cerebral dysfunction in patients with severe COVID-19 and methods for its early identification is warranted.

Cerebral intestinal interaction in children with autism spectrum disorder

Background. Autism spectrum disorders (ASD) in children are associated with features of neuropsychological development, characterized by socio-communicative, emotional, and behavioral problems. The processes of interaction between the central and enteric nervous systems, taking into account the inherent RAS reactions of autonomic maladaptation, endogenous stress, eating behavior determine the pathophysiological mechanisms underlying the comorbid pathology of the digestive system. The study was aimed to analyze the cerebral intestinal interaction signs in children with ASD, taking into account the role of NSE and S-100 neurotransmitters. Materials and methods. Sixty-six children with ASD were examined, out of which 45 children had concomitant functional disorders of the digestive system (FDDS). Clinical manifestations of ASD were assessed by the CARS scale; FDDS was diagnosed based on the Rome IV criteria. Serum levels of NSE neurotransmitters and S-100 protein were measured immunochemically. The patients were examined after obtaining informed consent in compliance with the principles of bioethics. Results. According to the data obtained in children with ASD, the frequency of concomitant FDDS is 68.20 %. In this case, ASD in combination with functional disorders of the biliary tract (FDBT) is observed in 22.7 %, with irritable bowel syndrome (IBS) — in 27.30 %, with syntropic FDDS — in 18.20 % of patients. The study traced the association between severe ASD and concomitant FDDS, in particular ASD with isolated IBS (p = 0.004), ASD with isolated FDBT (p = 0.009), ASD with syntropic functional disorders (p = 0.041). Increased serum concentrations of the NSE and S-100 neurotransmitters have been observed in children with concomitant FDDS. The level of S-100 protein and clinical manifestations of FDDS reveal a correlation, the degree of which increases in the following sequence: IBS (r = 0.34), and syntropic FDDS (r = 0.48). Conclusions. Peculiarities of cerebral intestinal interactions in ASD determine the high frequency of FDDS, in the structure of which IBS dominated. The presence of concomitant pathology impacts the clinical manifestations of ASD, complicating its course to a greater extent in cases of syntropic FDDS. Involvement of enteric glial structures in ASD is accompanied by the NSE and S-100 neurotransmitters level increase on the background of concomitant FDDS. The diagnostic value of S-100 protein in IBS in children with ASD is shown.

Correlation of Serum S-100 Protein Level with Severity of Ischaemic Stroke

Background: Stroke is currently the second leading cause of death worldwide and the first leading cause of death in Bangladesh. The National Institute of Health Stroke Scale is the most commonly used deficit rating scale to assess stroke severity. S-100 protein is a low molecular weight calcium-binding protein expressed mostly in glial cells like astrocytes, oligodendrocytes, and microglial cells. During the ischaemic process, S-100 protein is secreted from the glial cells into the extracellular space. After secretion, S-100 protein releases initially into the cerebrospinal fluid and then eventually into the bloodstream due to disruption of the blood-brain barrier. Aim of the study: To correlate serum S-100 protein level with the severity of ischaemic stroke. Methods: This cross-sectional study was conducted at the Department of Laboratory Medicine in collaboration with the Department of Neurology, BSMMU, Dhaka, Bangladesh from September 2018 to August 2019. A total of 70 ischaemic stroke patients were enrolled in this study. After taking proper history and neurological examination, the severity of ischemic stroke was assessed on the basis of NIHSS score. Then, serum S-100 protein levels were measured by the Electrochemiluminescence Immunoassay method. Statistical analysis was done by SPSS version 22.0. Results: According to the NIHSS scores, 35(50.0%) of the patients had moderate stroke (NIHSS score=5-15), 17(24.3%) had minor stroke (NIHSS=1-4), 12(17.1%) had moderate to severe stroke (NIHSS=16-20) and 4(5.0%) had severe stroke (NIHSS=21-42). The mean S-100 protein level was found 0.283±0.165 μg/L. Mean S-100 protein levels was assessed in different categories of severity of ischaemic stroke. Maximum Mean± SD value of serum S-100 protein was found in case of severe stroke (NIHSS score=21-42; Mean ± SD: 0.739±0.207, range: 0.523-1.019). The significance test was done by ANOVA test which was found statistically significant (p-value &lt;0.001). Pearson’s correlation test revealed a significant strong positive correlation (r=+943, p&lt;0.001) between serum S-100 protein level and NIHSS scores of ischaemic stroke patients. Conclusion: In the present study it was found that serum S-100 protein levels were higher in severe ischaemic stroke in relation to the ischaemic stroke of lower severity. S-100 protein level is rapidly determined by the method used in the present study. Serum S-100 protein level in this regard can be used as an important tool to predict the severity of ischaemic stroke. Further study is needed to confirm the findings of the present study.

Risk Factors and Serum S-100 Protein Level Analysis of Ischaemic Stroke Patients: A Tertiary Care Hospital Study in Bangladesh

Background: Information regarding the associated risk factors is very important in treating patients with ischaemic stroke besides severity measurement. The National Institute of Health Stroke Scale (NIHSS) is the most commonly used deficit rating scale to assess stroke severity. Serum S-100 protein is a low molecular weight calcium-binding protein expressed mostly in glial cells like astrocytes, oligodendrocytes, and microglial cells. During ischaemic process, S-100 protein is secreted from the glial cells into the extracellular space. After secretion, S-100 protein releases initially into the cerebrospinal fluid and then eventually into the bloodstream due to disruption of the blood-brain barrier. Aim of the study: The aim of this study was to assess risk factors and Serum S-100 protein level of ischaemic stroke patients. Methods: This cross-sectional study was conducted at the Department of Laboratory Medicine in collaboration with the Department of Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from September 2018 to August 2019. A total of 70 patients with ischaemic stroke from the Department of Neurology, BSMMU were enrolled in this study. After taking proper history and neurological examination, the severity of ischemic stroke was assessed on the basis of NIHSS score. Then, serum S-100 protein levels were measured by Electrochemiluminiscence Immunoassay (ECLIA) method. Statistical analysis was done by SPSS version 22.0. Results: In this study, as risk factors, maximum patients 45(64.3%) had hypertension followed by dyslipidemia 34(48.6%), diabetes mellitus 23(32.9%), heart disease 22(31.4%), history of previous vascular events 9(12.9%) and family history of stroke 8(11.4%). In assessing the relationship among severity of ischaemic stroke with Serum S-100 protein level we observed that the mean ± SD S-100 protein level was found 0.283± 0.165 μg/L with the range of 0.103-1.019 μg/L. Mean± SD levels of serum S-100 protein .....

Comparative Characterization of Candidate Molecular Markers in Ischemic and Hemorrhagic Stroke

According to epidemiological studies, the leading cause of morbidity, disability and mortality are cerebrovascular diseases, in particular ischemic and hemorrhagic strokes. In recent years considerable attention has been given to the study of molecular markers of ischemic and hemorrhagic strokes. These studies are relevant because brain-specific protein biomarkers of neurons and glial cells can provide valuable and timely diagnostic information necessary for clinical decision-making.The aim of the study was to reveal the differences in the serum level of molecular markers in acute, subacute and early recovery periods of ischemic and hemorrhagic strokes.Material and methods. The study included 59 patients. Twenty patients were diagnosed with hemorrhagic stroke and 39 had ischemic stroke. The control group included 20 volunteers. Serum levels of molecular CNS markers were determined in acute, subacute, and early recovery stages of stroke. The serum levels of CNS molecular markers of patients with ischemic and hemorrhagic stroke was measured quantitatively by enzyme immunoassay. Statistical analysis was performed by nonparametric Mann-Whitney method.Results. The level of brain-derived neurotrophic factor (BDNF) in the control volunteers was 574.5 [455.5; 615] pg/ml. Significant differences were found for acute and subacute periods of hemorrhagic stroke: it was 674 [560; 749] pg/ml (P=0.003) and 664 [616; 762] pg/ml (P=0.0001).The level of neuron-specific enolase was significantly increased in all periods of the study: it was 4.15 [3.53; 4.8] ng/ml in the control group, 5.4 [4.4; 6.4] ng/ml in acute period of ischemic stroke (P&lt;0.001), 5.4 [4.4; 6.4] ng/ml in early recovery period of ischemic stroke (P=0.001), 5.1 [4.6; 6.4] ng/ml in acute period of hemorrhagic stroke (P=0.014), 664 [616; 762] ng/ml in subacute period of hemorrhagic stroke (P=0.003).In the control group, the serum S-100 protein level was 4.5 [3.8; 5.4] ng/ml. In the acute and early recovery periods of ischemic stroke, S-100 protein level has significantly fallen down to 4.1 [3.4; 4.6] ng/ml (P&lt;0.031) and 3.9 [3.4; 6] ng/ml (P=0.014), respectively. Glial-cell derived neurotrophic factor level was 1.98 [1.64; 2.1] ng/ml in the controls and increased up to 2.4 [2.2; 5] ng/ml (P=0.002) in the acute period and 2.4 [2.3; 2.6] ng/ml (P&lt;0.001) in the subacute period of hemorrhagic stroke.The vascular endothelial growth factor receptor-1 (VEGFR-1) was significantly lower in the subacute period of hemorrhagic stroke: 485 [211; 945] pg/ml in the subacute period vs 903.5 [626; 1115] pg/ml in the controls (P=0.001).Conclusion. We found differences in the serum level of molecular markers in patients with ischemic and hemorrhagic strokes. In the acute period, early recovery period of ischemic stroke, and subacute period of hemorrhagic stroke, there was an increase in the serum level of neuron-specific enolase. The level of brain-derived neurotrophic factor increased significantly in the acute and subacute periods of hemorrhagic stroke. In the acute and early recovery periods of ischemic stroke, the level of S-100 protein decreased. The level of glial cell-derived neurotrophic factor increased in the acute and subacute periods of hemorrhagic stroke. In the subacute period of hemorrhagic stroke, the level of endothelial growth factor receptor-1 significantly decreased. Moreover, there was significant difference between values of this parameter in the subacute period of hemorrhagic stroke and in the early recovery period of ischemic stroke.

Роль биохимических маркеров в патогенезе, диагностике и прогнозировании острой церебральной ишемии

В статье приведены данные литературы о современной выживаемости и смертности от церебрального инсульта. Показана роль гематоэнцефалического барьера и сосудистого эндотелия в патогенезе повреждения мозговой ткани с развитием воспалительных нейроаутоиммунных нарушений. Доказано, что критерием тяжести инсульта являются лабораторные определения показателей провоспалительных и противовоспалительных цитокинов, С-реактивного белка. Также важную диагностическую и прогностическую роль в динамике течения инсультной болезни играют нейроспецифические белки. Определение уровней белка S100 и нейроспецифической энолазы дает возможность выявить выраженность поражения нейронов и клеток глии, прогнозировать клиническое течение, исход заболевания, осуществлять мониторинг его лечения. Поэтому важнейшим аспектом фундаментальных исследований в ангионеврологии является изучение биохимических нарушений при ишемии мозга, что позволяет расширить понимание сложных механизмов патогенеза инфаркта мозга, разработать терапевтические подходы к коррекции его лечения. Таким образом, исследование биохимических маркеров позволяет оценить тяжесть деструктивных изменений ткани головного мозга, нарушения целостности гематоэнцефалического барьера, прогнозировать течение и завершение острой церебральной ишемии.

The Influence of Different Dexmedetomidine Doses on Cognitive Function at Early Period of Patients Undergoing Laparoscopic Extensive Total Hysterectomy.

Background This study aims to analyze the influence of different dexmedetomidine doses on cognitive function. It works on early periods of patients undergoing laparoscopic extensive total hysterectomy. Method 119 patients with gynecological cancer underwent a laparoscopic extensive total hysterectomy. The operation was performed at the Affiliated Women's and Children's Hospital of Xiamen University from January 2019 to June 2020. The score of MoCA and the level of TNF-α, IL-6, S-100β protein, NSE, and GFAP of each group were compared 1 day before and after operation and 3 and 7 days after operation. Result In four groups, remifentanil, sufentanil, and propofol were given in the following order: group A > group D > group C > group B. Group A > group D > group C in terms of time spent in the recovery room, extubation, and recovery from anesthesia. The difference between groups B and C was not significant (P > 0.05). Compared with group A, group B scored higher in MoCA at 1 day (T1), 3 days (T2), and 7 days (T3) after operation (P < 0.05). At the same scoring point, the score was group B > group C > group D > group A. The POCD of four groups all occurred at 3 days after surgery. Compared with the T0 point, the level of TNF-α and IL-6 of the four groups at T1 and T2 was significantly increased (P < 0.05). At T3, the level of TNF-α and IL-6 gradually decreased. At various periods, the levels of S-100 protein, NSE, and GFAP in groups B, C, and D were lower than those in group A (P0.05). Group B had a substantially higher rate of bradycardia than the other three groups (P0.05). The incidence of chills, respiratory depression, and restlessness in group A differed significantly from the other three groups (P < 0.05). Conclusion Using 0.5 μg/kg dexmedetomidine during the perianaesthesia can effectively reduce anesthetic drugs in patients. They had a laparoscopic extensive complete hysterectomy, which helps to reduce the adverse responses and the occurrence of POCD while also protecting brain function.

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 &lt; 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.

ОЦЕНКА ИСХОДНОГО СТАТУСА ПАЦИЕНТОВ С ПОЛИТРАВМОЙ КАК ОСНОВНОЙ КОМПОНЕНТ СТРАТЕГИИ АНАЛГОСЕДАЦИИ ПАЦИЕНТОВ В ОИТ

Известно, что хирургическое вмешательство вызывает воспалительную реакцию, величина которой зависит от типа операции и степени повреждения ткани [2]. Эта послеоперационная воспалительная реакция сопровождается депрессией клеточного иммунитета, что в свою очередь предрасполагает пациентов к послеоперационным инфекциям и сепсису. Еще одной проблемой, выявленной нами, является то, что оценка влияния препаратов в ОИТ начинается как бы «с чистого листа», без учета уже имеющихся изменений в соматическом, иммунном и гормональном состояниях, связанных как с самим фактом травмы, так и с фактом оперативного вмешательства и уже имеющимся влиянием препаратов для общей анестезии на пациентов с политравмой. Цель исследования. Определить исходный статус пациентов с политравмой при поступлении в ОИТ для разработки превентивной стратегии аналгоседации, что выполняется впервые.Материал и методы. В исследовании участвовали 78 пациентов с политравмой, находящихся в ОИТ, из которых 62,8% составили мужчины и 37,2% – женщины. Средний возраст всех пациентов – 52,2±3,5 года. Сбор анамнеза и жалоб пациентов включал в себя оценку по шкалам SOFA, GCS, MRS, MMSE. Оценивались уровни белка S-100 и цилиарный нейротрофический фактор (CNTF).Результаты и обсуждение. Оценив по шкале SOFA, мы установили, что лишь 30% пациентов с политравмой требуют перевода в ОИТ с длительной ИВЛ и аналгоседацией. Эти пациенты пребывают в состоянии выраженного иммунодефицита и требуют комплексного подхода к лечению. Заключение. Пациентам на длительной ИВЛ необходимо тщательно подбирать стратегию аналгоседации с учетом исходного состояния и биоритмологических особенностей. Необходимо тщательно подбирать режимы ИВЛ, следить за оксигенацией. Немаловажным этапом лечения является подбор нутритивной поддержки с наиболее ранним переходом на энтеральное питание. Заключительным этапом является индивидуальный подбор антибиотикотерапии для предотвращения осложнений ИВЛ.

820: Elevated plasma S100 protein levels in preterm gestations with histologic chorioamnionitis

Histologic chorioamnionitis (HCA) is an inflammatory process that may be clinically silent and linked with preterm birth. S100 proteins are inflammatory markers which have been identified in amniotic fluid of mothers affected by HCA. We explored the relationship of S100A8 and S100A12 levels in mother-baby pairs with HCA compared to unexposed controls. We hypothesized that S100 protein expression levels are increased in mother-baby pairs affected by HCA. This is a prospective observational cohort of singleton or uncomplicated twin gestations from 230/7 to 346/7 weeks with preterm labor or preterm premature rupture of membranes (PPROM). Exclusion criteria included any maternal inflammatory disorder. Maternal peripheral blood was obtained within 24 h peripartum and venous umbilical cord blood samples were obtained at delivery. Diagnoses of maternal (M-HCA) or fetal (F-HCA) or the absence of HCA (Ctrl) were determined by placental examination per Redline HCA definitions (Redline 2012). S100A8 and S100A12 levels were measured by commercial ELISA. Data were analyzed using appropriate statistical methods. S100 protein levels were determined in plasma samples from 41 mother-baby pairs (7 M-HCA, 22 F-HCA, 12 Ctrl). Demographic data, PPROM incidence and gestational age at delivery were similar between groups. In F-HCA, S100A8 levels were increased 2-fold in maternal blood (p< .05) and 4-fold in cord blood (p< .001) relative to Ctrl. In F-HCA, maternal and cord blood S100A8 levels were similar, but in M-HCA, maternal levels were higher (p=.01). Cord blood S100A12 levels were 4-fold higher with F-HCA vs. Ctrl (p< .0001). In contrast, maternal S100A12 levels were similar across conditions. Fetal HCA is associated with elevated S100A8 and S100A12 levels in maternal and neonatal plasma. Our data suggest that maternal S100A8 blood levels may uniquely identify fetal HCA, a diagnosis that currently depends on postpartum placental analysis. Studies to establish the utility of S100A8 as a biomarker of HCA in a more extensive population are planned.

The interconnection between the postoperative cognitive dysfunction, the S100 protein and BNDF levels in patient after the coronary bypass graft surgery

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