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

Analgesics — still a nephrological cause for concern?

Nefropatia analgetyczna w swojej klasycznej formie powoli przechodzi do historii medycyny. Ma to związek z zakazem stosowania fenacetyny, wprowadzanym konsekwentnie w kolejnych krajach w II połowie XX wieku. Kwestia nefrotoksyczności innych leków przeciwbólowych czy przeciwzapalnych, w tym pochodnej fenacetyny — paracetamolu, jest przedmiotem badań i kontrowersji. Teoretyczne mechanizmy ich szkodliwości są znane i dość dobrze udokumentowane w badaniach doświadczalnych, dowodów klinicznych jest zaś znacznie mniej. W niniejszym artykule opisano genezę i obraz nefropatii analgetycznej oraz jej wpływ na przewlekłą chorobę nerek w wieku XX i obecnie. Przedstawiono również aktualnie obowiązujące poglądy na nefrotoksyczność stosowanych współcześnie leków przeciwbólowych i przeciwzapalnych.Analgesic nephropathy, in its classic form, slowly fades into history. This is a result of the fenacetin ban, consequently introduced in consecutive countries during the second half of the XX century. Potential nephrotoxicity of other analgesic and anti-inflammatory drugs, including paracetamol, a phenacetin metabolite, remains a matter of studies and debate. Theoretical mechanisms of their nephrotoxicity are well known, and supported by the results of experimental studies. However, the clinical proofs are lacking. The present article describes the genesis and clinical picture of analgesic nephropathy, as well as its contribution to the epidemiology of chronic kidney disease in the XX century and at present. Up to date opinions on the nephrotoxicity of currently utilized analgesic and anti-inflammatory drugs are presented

TF and TFPI in myeloproliferative neoplasms — a preliminary study

Introduction. Haemostatic disturbances such as thrombosis or diathesis are frequent complications in patients with myeloproliferative neoplasms (MPNs). The purpose of this study was to evaluate the concentration of tissue factor (TF), tissue factor pathway inhibitor (TFPI), and thrombin–antithrombin (TAT) complexes in patients with MPNs.Patients and methods. The study involved 43 patients with MPNs (mean age 60.5 years), including 16 patients with essential thrombocythaemia, eight with polycythaemia vera, ten with chronic myeloidleukaemia, and nine with primary myelofibrosis. The control group consisted of 30 healthy volunteers who were age- and sex-matched. TF, TFPI and TAT complexes concentration were measured using the immunoenzyme method.Results. TF and TAT complex concentrations were significantly higher, but the TFPI concentration was lower, in the total study group compared to the control group. TF concentration in each of the subgroups was significantly higher than in the control group. TFPI concentration was significantly lower in essential thrombocythaemia and polycythaemia vera than in controls. In addition, the concentration of TAT complex in patients with chronic myeloid leukaemia was significantly higher than in the control group.Conclusions. Elevated TF levels and decreased TFPI levels in patients with essential thrombocythaemia and polycythaemia vera indicate the activation of blood coagulation process depending on the TF (an extrinsic pathway). These patients represent a group at high risk of thrombotic complications

BDNF and IL-8, But Not UCHL-1 and IL-11, Are Markers of Brain Injury in Children Caused by Mild Head Trauma

The aim of the study was to check whether the plasma levels of brain-derived neurotrophic factor (BDNF), interleukin-8 (IL-8), interleukin-11 (IL-11) and ubiquitin C-terminal hydrolase L1 (UCHL-1) change in children with mild head trauma (N = 29) compared to controls (N = 13). Protein concentration in children with mild head trauma (12 children with mild concussion without loss of consciousness and 17 children with severe concussion and loss of consciousness) and the control group were measured by means of the Enzyme-Linked Immunosorbent Assay (ELISA) method. IL-8 and BDNF concentration was statistically higher in the group of children with mild head trauma (9.89 pg/mL and 2798.00 pg/mL, respectively) compared to the control group (7.52 pg/mL and 1163.20 pg/mL, respectively). BDNF concentration was significantly higher in children with severe concussion and loss of consciousness (3826.00 pg/mL) than in the control group. None of the tested proteins differed significantly between children with mild concussion without loss of consciousness and children with severe concussion and loss of consciousness. BDNF and IL-8 may be sensitive markers of brain response to mild head trauma in children. The lack of statistical differences for BDNF and IL-8 between children with mild or severe concussion could indicate that their elevated levels may not result from significant structural brain damage but rather reflect a functional disturbance

Concentration of UHCL1 in the Serum of Children with Acute Appendicitis, Before and After Surgery, and Its Correlation with CRP and Prealbumin

Ubiquitin-mediated protein degradation plays a crucial role in various cellular processes, including signal transduction, cell differentiation, and stress response. Ubiquitin C-terminal hydrolase 1 (UCHL1) is a unique deubiquitinating enzyme that has both hydrolase and ligase activities. The aim of this study was the determination of UCHL1 concentration in serum of children with appendicitis, before and after the surgery. Material and methods: 42 children with acute appendicitis, who were managed at the Pediatric Surgery Department, between 2013 and 2014, were randomly included into the study (age 9 months up to 14 years, mean age 2.5 + 1 years). There were 15 girls and 27 boys. 18 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. Results: The UCHL1 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, the difference was statistically significant. The UCHL1 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: UCHL1 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 UCHL1 concentration in children with appendicitis. There is strong negative correlation between prealbumin and UCHL1 concentrations

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

Levels of Selected Matrix Metalloproteinases—MMP-1, MMP-2 and Fibronectin in the Saliva of Patients Planned for Endodontic Treatment or Surgical Extraction

Objectives: Composition of saliva reflects the condition of the oral cavity. The aim of the study: Investigation of the concentrations of MMP-1 (Matrix metalloproteinase-1), MMP-2 (Matrix metalloproteinase-2) and fibronectin in the saliva of patients planned for endodontic treatment or surgical extraction. Material and methods: Seventy-five patients with caries and 14 healthy subjects were included in the study. Subjects were divided into group 1, in which 50 patients were planned for endodontic treatment, and group 2, in which 25 patients were planned for surgical extraction. For the measurements, we used a surface plasmon resonance imaging biosensor. Results: We found higher levels of MMP-1, MMP-2 and fibronectin in the saliva of patients planned for dental treatment than in healthy donors. We found lower concentrations of MMP-2 in subjects planned for surgical extraction, than in patients planned for endodontic treatment; however, there were no such differences in salivary concentrations of MMP-1 and fibronectin. There were no statistically significant differences in MMP-1 concentrations in the saliva before and after any type of dental treatment, but contrary to that, we found a statistically significant decrease in MMP-2 concentrations after endodontic treatment and after surgical extraction. We found a significant rise in the concentrations of fibronectin after surgical extraction but not after endodontic treatment. Conclusions: The concentrations of MMP-1 and MMP-2 in the saliva of our patients with caries were increased in comparison to healthy individuals, but after the treatment&mdash;so sanation of the oral cavity&mdash;we noted a decrease in matrix metalloproteinases (MMPs) levels. MMPs can be found in gingival crevicular fluid and saliva, carious dentin and plaque. According to our observations, the main source of MMPs in patients with caries is probably carious dentin. Increase in the salivary levels of fibronectin (FN) after surgical extraction may be connected with soft tissue injury caused by surgical extraction. Our results are another example of the fact that higher salivary concentrations of MMP-1, MMP-2 and FN can reflect the health status of the oral cavity in patients with caries

Overexpression of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in boys with cryptorchidism.

BACKGROUND:The ubiquitin-proteasome system regulate p53, caspase and Bcl-2 family proteins, and is crucial for the degradation of the defective germ cells in testes. Purpose: to evaluate the concentration of ubiquitin carboxyl-terminal hydrolase 1 (UCHL1) in the blood plasma of boys with cryptorchidism and if there is any correlation with patient age. METHODS:Patients-50 boys aged 1-4 years (median = 2,4y.) with unilateral cryptorchidism. Exclusion criteria were: previous human chorionic gonadotropin treatment, an abnormal karyotype, endocrine or immunological disorders or any long-term medication. The control group-50 healthy, age matched boys (aged 1-4 years, median = 2,1y.), admitted to the Pediatric Surgery Department for planned herniotomy. To investigate UCHL1 in blood plasma of boys with cryptorchidism, we used a novel technique Surface PLASMON RESONANCE Imaging (SPRI). RESULTS:The median concentration of UCHL1 in the blood plasma of boys with cryptorchidism, was 5-folds higher than in boys with inguinal hernia, whose testicles were located in the scrotum. We also noticed statistically significant difference between UCHL1 levels in boys with cryptorchidism up to 2 years old, and above 2 years old. Older boys, whose testicles since birth were located in the inguinal pouch or in the abdominal cavity, had higher concentration of UCHL1 in their blood plasma, than boys from younger group. In the group of cryptorchid boys, we also found slightly lower concentrations of INSL3, without statistical significance and no correlation with UCHL1 levels. CONCLUSIONS:Uchl1 concentrations in the blood plasma of boys with cryptorchidism, may reflect the heat-induced apoptosis of germ cells. Higher UCHL1 concentrations in older boys with undescended testicles, probably express intensity of germ cell apoptosis, more extensive when testicles are subjected to heat-stress for longer period. Further analyses of UCHL1 may help to elucidate its role in mechanisms influencing spermatogenesis