20S constitutive proteasome, 20S immunoproteasome, and cathepsin S are high-sensitivity and independent markers of immunological activity in relapsing-remitting type of multiple sclerosis.

Research on the markers of autoimmune response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface plasmon resonance imaging (SPRI) biosensors were used for the evaluation of protein concentrations. Plasma 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S concentrations were significantly higher in RRMS patients compared to the control group. All three parameters were characterized by excellent usefulness in differentiating MS patients from healthy individuals (AUC equal to or close to 1.000). The plasma concentration of analyzed parameters was not correlated with severity of disability in the course of RRMS (EDSS value), the number of years from the first MS symptoms, the number of years from MS diagnosis, or the number of relapses within the 24-month observational period. Our study has shown that plasma concentrations of 20S constitutive proteasome, 20S immunoproteasome, and cathepsin S have promising potential in differentiating RRMS patients from healthy individuals. All of the analyzed parameters were found to be independent of the time of MS relapse and the severity of neurological symptoms. Hence, their potential as highly sensitive and independent circulating markers of RRMS suggests a stronger association with immunological activity (inflammatory processes) than with the severity of the disease.

Ubiquitin carboxy-terminal hydrolase L1 - physiology and pathology.

Ubiquitin C-terminal hydrolase 1 (UCHL1) is an enzyme unique for its multiple activity - both ligase and hydrolase. UCHL1 was first identified as an abundant protein found in the brain and testes, however its expression is not limited to the neuronal compartment. UCHL1 is also highly expressed in carcinomas of various tissue origins, including those from brain, lung, breast, kidney, colon, prostate, pancreas and mesenchymal tissues. Loss-of-function studies and an inhibitor for UCHL1 confirmed the importance of UCHL1 for cancer therapy. So far biological significance of UCHL1 was described in the following processes: spermatogenesis, oncogenesis, angiogenesis, cell proliferation and differentiation in skeletal muscle, inflammation, tissue injury, neuronal injury and neurodegeneration.

Intraoperative Peritoneal Interleukin-6 Concentration Changes in Relation to the High-Mobility Group Protein B1 and Heat Shock Protein 70 Levels in Children Undergoing Cholecystectomy.

The aim was the evaluation of IL-6 concentration in peritoneal lavage fluid of children which underwent cholecystectomy to ascertain if there is a difference in early inflammatory response depending on the type of surgical approach (open vs. laparoscopy). The analysis of high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70) was performed to find out if the source of IL-6 was related to tissue damage. IL-6 concentration in peritoneal lavage fluid samples, obtained at the beginning and at the end of the laparoscopic (N = 23) and open cholecystectomy (N = 14), was tested with a routinely used electrochemiluminescence assay. The concentrations of HMGB1 and HSP70 were analyzed with the use of an ELISA method. Statistical analysis was performed using the STATISTICA PL release 12.5 Program. The differences were assessed using the Mann-Whitney U test and Wilcoxon matched pairs test. Correlations were studied by using the Spearman correlation test. Our results demonstrated significant peritoneal lavage fluid IL-6 concentration growth measured at the end of the cholecystectomy as compared to the beginning, regardless of the type of the procedure. IL-6 growth during open cholecystectomy was greater compared to laparoscopic cholecystectomy (62.51-fold vs. 3.19-fold). IL-6 concentration did not correlate with HMGB1 and HSP70, which indicate that the significant growth of this cytokine was not related to mechanical tissue damage due to surgical procedure. A clinical significance of the study could be related to the fact that the evaluation of IL-6 concentration in peritoneal lavage fluid may be useful to assess an early local inflammatory response.

Plasma concentration of MMP-1 and MMP-2 in boys with cryptorchidism and its lack of correlation with INSL3 and inhibin B.

The matrix metalloproteinases are enzymes capable of remodeling of extracellular matrix, and modulate the behavior of cells. Maturation of gubernaculum and spermatogenesis demand proper equilibrium of metalloproteinases and their inhibitors. The aim of this survey was to investigate the levels of matrix metalloproteinase type 1 (MMP-1) and matrix metalloproteinase type 2 (MMP-2) in the plasma of children with unilateral cryptorchidism along with levels of Insulin-like Peptide 3 (INSL3) and inhibin B. INSL3 have a role in gubernaculum development. Inhibin B is produced by Sertoli cells, and its levels reflect the status of the testis germinative epithelium. Fifty boys with an undescended testicle, aged 1-4 years (median = 2.4 years) were enrolled into the study. Fifty boys with inguinal hernia aged 1-4 years, served as controls (median age = 2.1 years). Investigators assessed the MMP-1 and MMP-2 concentrations using Surface Plasmon Resonance Imaging. The levels of INSL-3 and inhibin B were assessed using commercial enzyme-linked immunosorbent assay ELISA. The median concentration of MMP-1 and MMP-2 in the blood plasma of patients with unilateral cryptorchidism, was nearly 2-folds higher than in controls. The great area under the ROC curve with the cut off value of 0.865 for MMP-1, and 0.819 for MMP-2, indicates the high clinical sensitivity and specificity of the test of plasma levels of MMP-1 and MMP-2 for boys with cryptorchidism. The increased plasma levels of MMP-1 and MMP-2, probably reflect the level of apoptosis of the germ cells in undescended testicles, in response to the heat stress during the period of prepubertal testis development. In the group of cryptorchid boys, we found slightly lower concentrations of INSL3, without statistical significance and without correlation with MMP-1 and MMP-2 levels. There were no significant differences in the levels of inhibin B in the group of boys with cryptorchidism and boys with inguinal hernia and it also did not correlate with MMP-1 and MMP-2 concentrations.

Concentration of Proteasome in the Blood Plasma of Children with Acute Appendicitis, Before and After Surgery, and Its Correlation with CRP.

OBJECTIVE: The determination of 20S proteasome concentration in the blood plasma of children with appendicitis and its correlation with CRP. DESIGN AND SETTING: Thirty-one children with acute appendicitis, were randomly included into the study (age 5 years up to 17 years, mean age 11.5 + 1 years). PARTICIPANTS: There were 17 girls and 14 boys. Eighteen healthy, age-matched subjects, admitted for planned surgeries served as controls. Exclusion criteria were: severe preexisting infections, immunological or cardiovascular diseases that required long-term medication, and complicated cases of appendicitis with perforation of appendix and/or peritonitis. MAIN OUTCOME MEASURES: The 20S proteasome concentrations in the blood plasma of patients with acute appendicitis were highest before the surgery and were above the range of concentrations measured in controls, and the difference was statistically significant. RESULTS: The 20S proteasome concentration measured 24 and 72 h after the operation, slowly decreased over time, and still did not reach the normal range, when compared with the concentration measured in controls (p < 0.05). CONCLUSIONS: 20S proteasome concentration may reflect the metabolic response to acute state inflammation, and the process of gradual ebbing of the inflammation. The method of operation-classic open appendectomy, or laparoscopic appendectomy, does not influence the general trend in 20S proteasome concentration.

Proteasome Activity and C-Reactive Protein Concentration in the Course of Inflammatory Reaction in Relation to the Type of Abdominal Operation and the Surgical Technique Used.

Surgical tissue damage and the accompanying inflammatory response lead to proteasome activation, initiation of damaged protein degradation, and induction of acute-phase inflammatory response. The aim of this study was to investigate the rate of change in proteasome chymotrypsin-like (ChT-L) activity and C-reactive protein concentration depending on the degree of tissue damage and their correlation with prealbumin concentrations in children before and after abdominal surgery. This experimental study included children who underwent abdominal surgery between 2015 and 2017. Plasma prealbumin concentrations and C-reactive protein levels (CRP) were determined by standard biochemical laboratory procedures. Proteasome activity was assessed using a Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Elevation of plasma proteasome activity was noted in children after laparoscopic and open abdominal surgeries. However, 20S proteasome activity in children undergoing conventional open surgery was significantly higher (P < 0.05) than in patients subjected to laparoscopy. At the same time, an increase in the CRP level was observed. However, there was no correlation between C-reactive protein concentrations and the type of abdominal surgery while there was a correlation observed in the case of proteasomes. Proteasome activity correlates with the degree of surgical tissue damage and prealbumin concentrations. More invasive surgery leads to a stronger activation of the proteasome involved in removing proteins that were damaged due to the surgical procedure. Proteasomes are more specific markers because there is a correlation between proteasome activity and the type of abdominal surgery in contrast to C-reactive protein concentrations which are not different in response to surgery performed in regard to ovarian cysts or cholelithiasis.

Proteasome and C-reactive protein inflammatory response in children undergoing shorter and longer lasting laparoscopic cholecystectomy.

Operations of varying duration cause the release of a number of inflammatory mediators, in particular cytokines which lead to proteasome and acute-phase reactions. The purpose of this novel human study, was to characterize inflammatory response in children undergoing laparoscopic cholecystectomy, by analyzing changes in selected inflammatory mediators: C-reactive protein concentration and circulating 20S proteasome activity following surgical injury and to correlate them with the duration of the surgical procedure. Plasma C-reactive protein concentration (CRP) was determined by standard biochemical laboratory procedures. Proteasome activity in the plasma of children was assessed using Suc-Leu-Leu-Val-Tyr-AMC peptide substrate. Statistically significant increase in the plasma proteasome activity and C-reactive protein concentration, was noted (p < .05) in children after laparoscopic cholecystectomy. We found the correlation between the 20S proteasome activity and the length of the procedure. In children undergoing longer lasting laparoscopic cholecystectomy the proteasome activity was much higher than in patients having shorter surgical procedure. The CRP concentration and 20S proteasome activity significantly increase after surgery, but only 20S proteasome activity correlate with the length of the surgery. This may confirm that CRP is only an indicator of pathological state, while the function of the proteasomes is more complex because of their participation in the processes of repair and wound healing, and in the removal of damaged proteins.

VEGF-A, sVEGFR-1, and sVEGFR-2 in BCR-ABL negative myeloproliferative neoplasms.

BACKGROUND AND OBJECTIVE: Data from the literature indicate the relationship between the bone marrow microvessel density and the blood parameters of angiogenesis. The aim of this study was to evaluate selected parameters of angiogenesis (VEGF-A, sVEGFR-1, and sVEGFR-2) and their correlations with white blood cells, platelets, and red blood cells. MATERIALS AND METHODS: The study included 72 patients (mean age, 61.84 years) with myeloproliferative neoplasms (MPNs): essential thrombocythemia (ET) (n=46), polycythemia vera (PV) (n=19), and primary myelofibrosis (PMF) (n=7). Serum VEGF-A, sVEGFR-1, and sVEGFR-2 were determined using the ELISA assay. RESULTS: We observed a significantly higher level of VEGF-A and reduced concentrations of sVEGFR-1 and sVEGFR-2 in the whole group of patients with MPNs as compared to controls. Detailed analysis confirmed significantly higher level of VEGF-A and lower concentration of sVEGFR-2 in each subgroups of MPNs patients. However, sVEGFR-1 concentrations were significantly lower only in PV and ET patients. CONCLUSIONS: The study showed an increased level of VEGF-A, which may indicate the intensity of neoangiogenesis in the bone marrow. Decreased sVEGFR-1 and sVEGFR-2 in the blood of patients with MPNs may reflect consumption of these soluble receptors.

[Significance of increased and reduced proteasome activity in the pathomechanism of selected disorders]. / Znaczenie podwyzszenia i obnizenia aktywnosci proteasomów w patomechanizmie wybranych schorzen.

Proteasomes are structures responsible for the elimination of damaged and misfolded proteins. Thus, they also regulate the most important intracellular processes. Changes in their functions can lead to many molecular diseases. There are two possible disorders in the function of proteasomes. Their increasing activity causes excessive degradation of important cell proteins. On the other hand, their insufficiency can inhibit the degradation of pathological proteins and lead to their accumulation. The increase of proteasome activity and the degradation of important proteins are observed in many pathological disorders. Therefore the study of pharmacological methods using proteasome inhibitors has gained growing interest in the last years. This review summarizes recent findings regarding the role of proteasomes in pathogenesis of selected diseases and discusses the potential use of proteasomes in diagnosis of different disorders.

Circulating proteasome activity following mild head injury in children.

PURPOSE: The aim of the study is to characterize changes in circulating proteasome (c-proteasome) activity following mild traumatic brain injury in children. METHODS: Fifty children managed at the Department of Pediatric Surgery because of concussion-mild head injury was randomly included into the study. The children were aged 11 months to 17 years (median = 10.07 + -1.91 years). Plasma proteasome activity was assessed using Suc-Leu-Leu-Val-Tyr-AMC peptide substrate, 2-6 h, 12-16 h, and 2 days after injury. Twenty healthy children admitted for planned inguinal hernia repair served as controls. RESULTS: Statistically significant elevation of plasma c-proteasome activity was noted in children with mild head injury 2-6 h, 12-16 h, and 2 days after the injury. CONCLUSIONS: Authors observed a statistically significant upward trend in the c-proteasome activity between 2-6 and 12-16 h after the mild head injury, consistent with the onset of the symptoms of cerebral concussion and a downward trend in the c-proteasome activity in the plasma of children with mild head injury between 12-16 h and on the second day after the injury, consistent with the resolving of the symptoms of cerebral concussion. Further studies are needed to demonstrate that the proteasome activity could be a prognostic factor, which can help in further diagnostic and therapeutic decisions in patients with head injury.

Treatment of problematic infantile hemangiomas with propranolol: a series of 40 cases and review of the literature.

UNLABELLED: Infantile hemangiomas (IH) are neoplastic proliferations of endothelial cells which occur with an incidence of 10 to 12% within the first year of life. IH grow after birth and usually regress spontaneously, but still can lead to deformities when they are located in the facial areas of the lip, eyelid, nasal tip or the ear. We wanted to share our experience in the treatment of problematic IH with propranolol. A retrospective review of medical charts was performed for 40 consecutive children treated with propranolol because of problematic IH between 2009 and 2012. 40 patients (33 girls, 7 boys) with a median age of 4.2 months (aged 1 to 11 months) were treated because of problematic IH. Rapid improvement was reported in the first days of treatment in 38 patients. In one case we had to terminate the treatment because serious tachycardia developed within the first 48 hours after propranolol was started. In this case the patient benefited from alternative treatment with timolol maleate gel. 35 patients (87%) showed an excellent response with complete resolution of the lesion. 4 patients (10%) showed a good result with >50% reduction in the size of the hemangioma. Also a patient with residual IH after terminating oral propranolol benefited from topical treatment with timolol maleate gel. A minor side effect was poor weight gain during prolonged treatment in one patient and tachycardia in another patient in which case we had to terminate the treatment. CONCLUSIONS: Our observations show that gradually increasing the dosage of propranolol up to 3 mg/kg and gradually weaning the dosage is safe and effective in treatment of problematic IH. Timolol maleate gel should be considered as a complementary treatment for residual hemangiomas after terminating propranolol treatment or as an alternative treatment in patients who do not tolerate oral propranolol well.

The preliminary study suggests an association between NF-ĸB pathway activation and increased plasma 20S proteasome activity in intracranial aneurysm patients.

The significant role of increased activation of 20S proteasomes in the development of abdominal aortic aneurysms has been well-established in a mouse model. The available literature lacks similar studies concerning brain aneurysms. The aim of the study was to verify the hypothesis that patients with unruptured intracranial aneurysms (UIA) have increased 20S proteasome ChT-L activity compared to the control group of individuals without vascular lesions in the brain. In the next step, the relationship between the activity of 20S proteasomes ChT-L and precursor proteins from the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) family, namely NF-κB1 (p105), NF-κB2 (p100), NF-κB p65, and the inflammatory chemokine MCP-1, was examined. Patients with UIA had significantly higher 20S ChT-L proteasome activity compared to the control group. Patients with multiple aneurysms had significantly higher 20S proteasome ChT-L activity compared to those with single aneurysms. In patients with UIA, the activity of the 20S proteasome ChT-L negatively correlated with the concentration of NF-κB1 (p105) and NF-κB p65 precursor proteins and positively correlated with the concentration of the cerebrospinal fluid chemokine MCP-1. Our results may suggest that increased 20S proteasome ChT-L activity in UIA patients modulates inflammation in the cerebral arterial vessel via the MCP-1 chemokine as a result of activation of the canonical NF-κB pathway.

UCHL1, besides leptin and fibronectin, also could be a sensitive marker of the relapsing-remitting type of multiple sclerosis.

Research on the markers of immunoregulatory response in multiple sclerosis (MS) is still of great importance. The aim of our study was the evaluation of leptin, fibronectin, and UCHL1 concentrations as potential biomarkers of a relapsing-remitting type of MS (RRMS). Surface Plasmon Resonance Imaging (SPRI) biosensors were used for the evaluation of proteins concentrations in 100 RRMS patients and 46 healthy volunteers. Plasma leptin, fibronectin, and UCHL1 concentrations were significantly higher in RRMS patients compared to the control group (p < 0.001, respectively). UCHL1 concentration evaluation revealed the highest diagnostic sensitivity (100%) and negative predictive value (100%) in differentiating MS patients from healthy individuals. There was no significant difference in the UCHL1 concentrations depending on the patient's sex, the presence of relapse within the last 24 months, and the EDSS value (p > 0.05, respectively). In RRMS patients UCHL1 concentration positively correlated with fibronectin levels (r = 0.3928; p < 0.001). In the current cohort of patients plasma UCHL1 concentration was independent of the time of MS relapse and the severity of neurological symptoms. Thus current study may indicate that plasma UCHL1, besides leptin and fibronectin, also could be a promising high-sensitive potential biomarker of relapsing-remitting type of MS. However, these results should be validated with a larger group of patients, taking into account neuroimaging and cerebrospinal fluid analysis data, and by comparing them to patients with other neurological diseases as a control group.

Canonical NF-κB signaling pathway and GRO-α/CXCR2 axis are activated in unruptured intracranial aneurysm patients.

Activation of the nuclear factor kappa-B (NF-κB) stimulates the production of pro-inflammatory molecules involved in the formation of intracranial aneurysms (IA). The study aimed to assess the NF-κB p65 subunit and the GRO-α chemokine and its receptor CXCR2 concentrations in unruptured intracranial aneurysm patients (UIA, n = 25) compared to individuals without vascular changes in the brain (n = 10). It was also analyzed whether tested proteins are related to the size and number of aneurysms. Cerebrospinal fluid (CSF) and serum protein levels were measured using the ELISA method. Median CSF and serum NF-κB p65 concentrations were significantly lower, while median CSF GRO-α and CXCR2 concentrations were significantly higher in UIA patients compared to the control group. CSF and serum NF-κB p65 concentrations negatively correlated with the number of aneurysms. In UIA patients the median GRO-α concentration was two-fold and CXCR2 almost four-fold higher in CSF compared to the serum value. CSF GRO-α concentration positively correlated with the size of aneurysms.Significantly decreased CSF NF-κB p65 and significantly increased CSF GRO-α and its CXCR2 receptor concentrations in UIA patients compared to the control group may altogether suggest that the canonical NF-κB signaling pathway is activated and its target pro-inflammatory genes are highly expressed in UIA patients. However, to unequivocally assess the involvement of the classical NF-κB pathway with the participation of the NF-κB p65 subunit and the GRO-α/CXCR2 axis in the formation of IA, further in vivo model studies are needed.

Plasma concentration of Bisphenol A and leptin in patients with meningioma and glioma: A pilot study.

PURPOSE: Recent increase in incidence of meningiomas suggests the need to search for new risk factors. Leptin, a potentially pro-angiogenic and proliferative agent, could be a candidate for this role, as its expression correlates with body mass index (BMI). Because development of meningioma has also been linked to sex hormones, bisphenol A (BPA), a known xenoestrogen, can also be taken into consideration as a potential risk factor. The aim of this study was to determine plasma concentrations of both substances in patients with meningiomas and to match it to patients with gliomas - a group of brain tumors less hormone- and BMI-dependent. MATERIALS & METHODS: Concentrations of BPA and leptin were measured in plasma of 24 patients with low grade meningioma and in 29 patients with glioma, using gas chromatography-mass spectrometry (GC-MS) and ELISA kits, respectively. The concentrations of both substances in patients with neoplasms were interpreted in relation to their concentration in healthy population, published in recent reports. RESULTS: Free and conjugated BPA were present in both meningioma and glioma patients. Moreover, their concentrations far exceeded those reported in the healthy population. Nevertheless, the level of leptin revealed to be significantly higher in meningioma patients than in glioma patients. CONCLUSIONS: Occurrence of both meningioma and glioma may be accompanied by increased concentrations of leptin and BPA. Further large-scale studies are needed to clarify whether the presence of both substances may play a role in pathogenesis or influence clinical course in patients with brain neoplasms.

Impact of the SARS-CoV-2 pandemic on the course and treatment of appendicitis in the pediatric population.

SARS-CoV-2 is a highly contagious virus causing mainly respiratory track disease called COVID-19, which dissemination in the whole world in the 2020 has resulted in World Health Organisation (WHO) announcing the pandemic. As a consequence Polish Government made a decision to go into a lockdown in order to secure the population against SARS-CoV-2 outbreak what had its major influence on the Polish Health Care System. All of the social and medical factors caused by the pandemic might influence children's health care, including urgent cases. The aim of this survey was the analysis of medical charts with focus on the course and results of surgical treatment of children who underwent appendectomy before and during the COVID-19 pandemic. Material and methods: We performed analysis of charts of 365 subjects hospitalized in the Pediatric Surgery Department from 1st January 2019 to 31st December 2020 because of acute appendicitis. Patients were divided into two groups-those treated in 2019-before pandemic outbreak, and those treated in 2020 in the course of pandemic. Results: the most common type of appendicitis was phlegmonous (61% of cases in 2019 and 51% of cases in 2020). Followed by diffuse purulent peritonitis (18% of cases in 2019 vs 31% of cases in 2020), gangrenous (19% of cases in 2019 vs 15% of cases in 2020) and simple superficial appendicitis (1% of cases in 2019 vs 3% of cases in 2020). There was statistically significant difference in the length of hospitalization: in 2019 the mean length of hospi-talization was 4.761 vs 5.634 in 2020. Laparoscopic appendectomy was performed more frequently before the COVID period (63% of cases treated in 2019 vs 61% of cases treated in 2020). In the pandemic year 2020, there was double increase in the number of conversion from the laparoscopic approach to the classic open surgery. In the year 2019 drainage of abdominal cavity was necessary in 22% of patients treated with appendectomy, in 2020 the amount of cases threated with appendectomy and drainage increased to 32%. Conclusions: fear of being infected, the limited availability of appointments at General Practitioners and the new organisation of the medical health care system during pandemic, delay proper diagnosis of appendicitis. Forementioned delay leads to higher number of complicated cases treated with open appendectomy and drainage of abdominal cavity, higher number of conversions from the laparoscopic to classic open technique, and longer hospitalization of children treated with appendectomy in the year of pandemic.

The Concentration of Selected Inflammatory Cytokines (IL-6, IL-8, CXCL5, IL-33) and Damage-Associated Molecular Patterns (HMGB-1, HSP-70) Released in an Early Response to Distal Forearm Fracture and the Performed Closed Reduction With Kirschner Wire Fixation in Children.

The evaluation of trauma after surgery through objective analysis of biochemical markers can help in selecting the most appropriate therapy. Thus the aim of the study was the evaluation of the concentration of selected inflammatory cytokines (IL-6, IL-8, CXCL5, IL-33), C-reactive protein (CRP), and damaged-associated molecular patterns (DAMPs): HMGB-1, HSP-70 in the plasma of children in response to bone fracture and 12-14 hours after subsequent surgery performed by closed reduction with percutaneous Kirschner wire fixation (CRKF). The study will answer the question if the CRFK procedure leads to excessive production of inflammatory and damage markers. Blood samples from 29 children with distal forearm fractures were collected 30 min. before CRKF procedure and 12-14 hours after performance of the procedure. The control group was composed of 17 healthy children. IL-6 and CRP concentrations were analyzed using routinely performed in vitro diagnostics tests; the remaining proteins were analyzed with the use of the ELISA method. Increased values of IL-6, CRP, and HSP-70 represented an early inflammatory response to distal forearm fractures classified as SH-II type according to the Salter-Harris classification system. However, the median CRP concentration was within the reference values not indicative of inflammation. The CRKF procedure may be a good solution for the treatment of bone fractures, as damaged associated molecular patterns - HMGB-1 and HSP-70 - did not significantly differ 12-14 hours after the approach was applied as compared to the control group. Moreover, the increase in IL-6 concentration after the CRKF procedure was 1.5-fold to the level before CRKF, while the increase of this marker in response to the distal forearm fracture was 4.3-fold compared to the control group. Based on this data, it appears reasonable to suggest that the CRKF approach caused less damage and inflammatory response in comparison to the response to the fracture itself.

Effects of combined Pulsed Dye Laser and Fractional CO2 Laser treatment of burn scars and correlation with plasma levels of collagen type I, MMP-2 and TIMP-1.

Hypertrophic burn scars remain a significant burden for patients and a challenge for clinicians. THE AIM: Assessement of the efficacy of combined Pulsed Dye Laser and Ablative Fractional CO2 Laser therapy on hyperthophic scars and correlation with plasma levels of MMP-2, TIMP-1 and alpha-1 type I collagen. PATIENTS AND METHODS: Twenty five pediatric subjects were enrolled into the study. Control group consisted of age-matched subjects admitted for surgical repair of inguinal hernia. For the assessment of the results of laser treatment we used the Vancouver scar scale (VSS), and Patient-Observer Scar Assessment Scale (POSAS). We also correlated clinical results with plasma levels of MMP-2, TIMP-1 and alpha-1 type I collagen. RESULTS: All subjects reported the laser treatment resulted in improvement and were somewhat satisfied or very satisfied with their experience. No adverse events were reported. The levels of MMP-2, TIMP-1 and alpha-1 type I collagen in our patients with scars before laser threatment were higher in comparison to controls. We also found statistically significant decrease in the levels of MMP-2, TIMP-1 and alpha-1 type I collagen after laser treatment of burn scars CONCLUSIONS: Our study clearly shows that combined CO2-AFL treatment for burn scars improve texture, colour, function and alleviate pruritus. We believe that decrease in the levels of MMP-2, TIMP-1 and alpha-1 type I collagen after laser treatment of burn scars, reflects reduced dynamic of scar.

IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm.

BACKGROUND: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. METHODS: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. RESULTS: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). CONCLUSION: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.

Myelin-associated proteins are potential diagnostic markers in patients with primary brain tumour.

INTRODUCTION: Taking into account the possibility of myelin-associated proteins having a role in brain tumour development, the study aimed to evaluate the diagnostic usefulness of myelin-associated proteins (Nogo-A, MAG, OMgp) released into extracellular space in patients with brain tumours. PATIENTS AND METHODS: Protein concentration in primary brain tumour (n = 49) and non-tumoural subjects (n = 24) was measured in cerebrospinal fluid (CSF) and serum by means of ELISA. Immunohistochemistry for IDH1-R132H was done on 5-µm thick formalin-fixed, paraffin-embedded tumour sections with the use of an antibody specific for the mutant IDH1-R132H protein. RESULTS: The receiver operator characteristic curve analysis showed that CSF Nogo-A and serum MAG were useful in differentiating patients with primary brain tumour from non-tumoural individuals. This was also true in the case of the separate analysis of the astrocytic tumour versus non-tumoural groups and the meningeal tumour versus non-tumoural groups. Neither Nogo-A nor MAG or OMgp concentrations were significantly different, in serum or CSF, between IDH1 wild-type astrocytic brain tumour patients compared to IDH1 mutant patients. CONCLUSIONS: Our results indicated the potential usefulness of CSF Nogo-A and serum MAG evaluation as circulating biomarkers of primary brain tumours. Because blood is relatively easy to obtain, future research should be conducted to explicitly indicate the value of serum MAG concentration evaluation as a brain tumour biomarker.Key messagesMyelin-associated proteins may be circulating brain tumour biomarkers.Nogo-A and MAG proteins seem to be the most useful in brain tumour diagnosis.Decreased CSF Nogo-A concentration is an adverse prognostic factor for patients' survival.