Universal nanocomposite coating with antifouling and redox capabilities for electrochemical affinity biosensing in complex biological fluids.

Electrochemical affinity biosensors have the potential to facilitate the development of multiplexed point-of-care diagnostics in complex biological fluids. However, their commercial viability has been hindered by challenges such as electrode biofouling and the lack of inherent redox properties. To address this unmet need, we have developed a universal nanocomposite coating which is unique in its ability to not only allow oriented conjugation of the biorecognition element but also specific detection directly in complex biological fluids like serum and urine owing to its built-in antifouling and redox capabilities, thus improving suitability for point of care testing. This multifunctional coating comprises a 3D porous crosslinked bovine serum albumin matrix for oriented conjugation and antifouling properties with embedded graphene nanosheets modified with amino-ferrocene for enhanced conductivity and mediator-free biosensing. The coating showed minimal signal degradation despite prolonged exposure to 1% bovine serum albumin, artificial urine and untreated human serum for up to 30 days. To demonstrate its utility, we fabricated and tested proof-of-concept electrochemical immunosensors for bladder cancer protein biomarkers, specifically interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The practical feasibility was highlighted by the excellent sensitivity and specificity observed for IL-8 and VEGF with a limit of detection of 41 pg mL-1 and 67 pg mL-1, respectively. Consequently, this universal nanocomposite-based electrochemical biosensing platform can be extended to the point of care testing of a broad spectrum of biomarkers present in complex biological fluids, thus enabling reliable and early diagnostics.

Urine soluble TLR4 levels may contribute to predict urinary tract infection in children: the UTILISE Study.

BACKGROUND: One of the most common bacterial infections in childhood is urinary tract infection (UTI). Toll-like receptors (TLRs) contribute to immune response against UTI recognizing specific pathogenic agents. Our aim was to determine whether soluble TLR4 (sTLR4), soluble TLR5 (sTLR5) and interleukin 8 (IL-8) can be used as biomarkers to diagnose UTI. We also aimed to reveal the relationship between urine Heat Shock Protein 70 (uHSP70) and those biomarkers investigated in this study. METHODS: A total of 802 children from 37 centers participated in the study. The participants (n = 282) who did not meet the inclusion criteria were excluded from the study. The remaining 520 children, including 191 patients with UTI, 178 patients with non-UTI infections, 50 children with contaminated urine samples, 26 participants with asymptomatic bacteriuria and 75 healthy controls were included in the study. Urine and serum levels of sTLR4, sTLR5 and IL-8 were measured at presentation in all patients and after antibiotic treatment in patients with UTI. RESULTS: Urine sTLR4 was higher in the UTI group than in the other groups. UTI may be predicted using 1.28 ng/mL as cut-off for urine sTLR4 with 68% sensitivity and 65% specificity (AUC = 0.682). In the UTI group, urine sTLR4 levels were significantly higher in pyelonephritis than in cystitis (p < 0.0001). Post-treatment urine sTLR4 levels in the UTI group were significantly lower than pre-treatment values (p < 0.0001). CONCLUSIONS: Urine sTLR4 may be used as a useful biomarker in predicting UTI and subsequent pyelonephritis in children with UTI. A higher resolution version of the Graphical abstract is available as Supplementary information.

Biomarkers for febrile urinary tract infection in children.

BACKGROUND: The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI. METHODS: This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls. RESULTS: We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children. CONCLUSIONS: NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

Albumin Urinary Excretion Is Associated with Increased Levels of Urinary Chemokines, Cytokines, and Growth Factors Levels in Humans.

The aim of the present study was to study the associations between urine albumin excretion, and a large number of urinary chemokines, cytokines, and growth factors in a normal population. We selected 90 urine samples from individuals without CVD, diabetes, stroke or kidney disease belonging to the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females, all aged 75 years). Urinary cytokine levels were analyzed with two multiplex assays (proximity extension assays) and the cytokine levels were correlated with urine albumin. After adjustment for sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), smoking and multiplicity testing, 11 biomarkers remained significantly associated with urine albumin: thrombospondin 2, interleukin 6, interleukin 8, hepatocyte growth factor, matrix metalloproteinase-12 (MMP-12), C-X-C motif chemokine 9, tumor necrosis factor receptor superfamily member 11B, osteoprotegerin, growth-regulated alpha protein, C-X-C motif chemokine 6, oncostatin-M (OSM) and fatty acid-binding protein, intestinal, despite large differences in molecular weights. In this study, we found associations between urinary albumin and both small and large urine proteins. Additional studies are warranted to identify cytokine patterns and potential progression markers in various renal diseases.

Interleukin 8 Is Overexpressed in Acute Rejection in Kidney Transplant Patients.

The main complication associated with renal graft loss is immune rejection. The gold standard for the diagnosis of renal graft rejection is percutaneous renal biopsy, which is expensive and can lead to complications. Inflammation is one of the main pathogenic pathways in allograft rejection, and urine samples seem to be efficient windows to explore the allograft condition with a high cost-benefit ratio. This study aimed to evaluate the messenger ribonucleic acid (mRNA) profile expression pattern for interleukin (IL) 2, IL-4, IL-6, IL-8, and IL-10; tumor necrosis factor alfa; gamma interferon; and transforming growth factor ß1 in the urine renal cells of patients with a diagnosis of humoral rejection and patients with a diagnosis of normal biopsy. METHODS: An observational, cross-sectional analytical study was performed. All kidney transplants were performed at the Organ Transplant Department between 2018 and 2019. Also, a healthy control with a normal blood test and no apparent infection was included. mRNA from urine samples and biopsies was isolated, and the expression of interleukins was analyzed in PCR real time. Data were analyzed by Shapiro-Wilk and Kruskal-Wallis tests. RESULTS: The proinflammatory IL expression pattern in urine samples of kidney rejection group showed overexpression for IL-8 (P = .0001). No differences were observed in the rest of the interleukins analyzed. When we compared the results in the rejected versus not rejected transplanted patients with a group of apparently healthy subjects, the difference remains consistent. Thus, mRNA of IL-8 could function as a diagnostic tool in cases of chronic damage secondary to fibrosis.

Novel Urinary Biomarkers for Diagnosis of Acute Pyelonephritis in Children.

Urinary tract infection (UTI) is common among pediatric population. Pyelonephritis, especially in young infants, is associated with a significant morbidity. Usually, clinical manifestations, laboratory findings, and imaging are used to differentiate between lower and upper UTI. Lack of specific clinical findings and commonly used nonspecific blood indices are important hamper differentiation between lower and upper UTI in early stages. Imaging techniques are neither cost benefit nor safe for detection of UTI. Recent efforts have focused on characterization of novel serum and urinary biomarkers for early detection of acute pyelonephritis in children. It seems that urinary NGAL, NAG, TNF-α and IL-8 may be used as novel markers for early diagnosis of acute pyelonephritis in children.

Identification of clinical and urine biomarkers for uncomplicated urinary tract infection using machine learning algorithms.

Women with uncomplicated urinary tract infection (UTI) symptoms are commonly treated with empirical antibiotics, resulting in overuse of antibiotics, which promotes antimicrobial resistance. Available diagnostic tools are either not cost-effective or diagnostically sub-optimal. Here, we identified clinical and urinary immunological predictors for UTI diagnosis. We explored 17 clinical and 42 immunological potential predictors for bacterial culture among women with uncomplicated UTI symptoms using random forest or support vector machine coupled with recursive feature elimination. Urine cloudiness was the best performing clinical predictor to rule out (negative likelihood ratio [LR-] = 0.4) and rule in (LR+ = 2.6) UTI. Using a more discriminatory scale to assess cloudiness (turbidity) increased the accuracy of UTI prediction further (LR+ = 4.4). Urinary levels of MMP9, NGAL, CXCL8 and IL-1ß together had a higher LR+ (6.1) and similar LR- (0.4), compared to cloudiness. Varying the bacterial count thresholds for urine culture positivity did not alter best clinical predictor selection, but did affect the number of immunological predictors required for reaching an optimal prediction. We conclude that urine cloudiness is particularly helpful in ruling out negative UTI cases. The identified urinary biomarkers could be used to develop a point of care test for UTI but require further validation.

[Predictors of perioperative complications in children with obstructive uropathy].

AIM: To identify predictors of perioperative complications in children with obstructive uropathy. MATERIALS AND METHODS: A total of 178 patients with obstructive uropathy were divided into 3 groups. In Group 1 there were 108 children with hydronephrosis, while Group 2 included 47 children with ureterohydronephrosis and Group 3 consisted of 23 children with bladder outlet obstruction according to the results of clinical, laboratory, microbiological, X-ray and pathologic study. The evaluation of the urine level of pro- (IL-8) and anti-inflammatory (IL-10) cytokines was performed at two timepoints, prior to treatment (1 point) and on the 3-5th day after the surgery (2 point) using "Vector - Best" (Russia, Novosibirsk) (IL-8), "Bender Medsystems" (Austria) (IL-10) on the enzyme immunoassay analyzer Stat Fax 2010 (USA). RESULTS: The active phase of chronic pyelonephritis was shown in Groups 1, 2 and 3 in 38%, 36% and 100% of cases, respectively. Microbiological examination of urine allowed to identify a causative agent in 85% and 89% of biopsy specimens from the ureteropelvic and ureterovesical junction, respectively. In all groups, Escherichia coli was a main pathogen (40%). In 25% of patients of Groups 1 and 2, isolated pathogens in biopsy specimen and urine were different. According to the evaluation of cytokines in the urine, during the active phase of chronic pyelonephritis there was an increase in the level of IL8 (p<0.0001) at points 1 and 2 in all patients. In the latent phase of inflammation, there was an increase in the concentration of IL-8 (p<0.04) and IL-10 (p<0.002) at point 2 in Groups 1 and 2. Using the ratio of IL-8 and IL-10, an index of inflammation activity (IIA) was suggested, whose values were increased in all Groups at point 1 and 2. Based on the regression analysis of the changes in IIA level, a model for predicting perioperative complications and an algorithm for personalized patient management were developed. CONCLUSION: Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.

Assessment the Effect of Dexamethasone on Urinary Cytokines and Renal Scar in Children with Acute Pyelonephritis.

INTRODUCTION: One of the most serious complications of acute febrilepyelonephritis in children is the development of renal scar. Thisstudy aimed to investigate the effect of dexamethasone on urinarycytokine levels and renal scar in children with acute pyelonephritis. METHODS: In a double-blind randomized clinical trial, 60 childrenaged 3 months to 12 years with acute febrile pyelonephritis enrolled.The experimental group was treated with a combination of antibioticand dexamethasone, and the control group underwent treatmentwith antibiotic and placebo. The urinary levels of interleukin -6(UIL-6) and -8 (UIL-8) were measured before treatment as baselineand were repeated four days later. RESULTS: 52 cases (23 patients with mean age of 34.19 ± 30.82 monthsin the dexamethasone group, and 29 patients with mean age of50.55 ± 44.41 months in the control group) completed the study. Inthe control group, the UIL-6 and UIL-8 level became significantlylower after four days treatment (P < .05). In the dexamethasonegroup, there was a statistically significant difference between bothUIL-6 and UIL-8 levels before and after treatment (P < .05). Inpatients who had scar on DMSA scan, the mean UIL-8 and UIL-6levels were significantly high before and after treatment. CONCLUSION: Results of this study showed that dexamethasone plusantibiotic have no clear superiority to antibiotic therapy alone indecreasing inflammatory cytokines and scar formation. We foundout that patients with scar had sustained high levels of biomarkersbefore and after treatment.

Biosensing using arrays of vertical semiconductor nanowires: mechanosensing and biomarker detection.

Due to their high aspect ratio and increased surface-to-foot-print area, arrays of vertical semiconductor nanowires are used in numerous biological applications, such as cell transfection and biosensing. Here we focus on two specific valuable biosensing approaches that, so far, have received relatively limited attention in terms of their potential capabilities: cellular mechanosensing and lightguiding-induced enhanced fluorescence detection. Although proposed a decade ago, these two applications for using vertical nanowire arrays have only very recently achieved significant breakthroughs, both in terms of understanding their fundamental phenomena, and in the ease of their implementation. We review the status of the field in these areas and describe significant findings and potential future directions.

Premenstrual Syndrome, Inflammatory Status, and Mood States in Soccer Players.

OBJECTIVE: To evaluate the relationship between the inflammatory profile and mood states in the different phases of the menstrual cycle in soccer players with and without premenstrual syndrome (PMS). METHODS: Data on the menstrual cycle and mood states were collected using the Daily Symptom Report and the Brunel Mood Scale. Cytokine and stress hormone concentrations were measured in urine by flow cytometry before and after a game in the luteal phase and in the follicular phase of one menstrual cycle. RESULTS: In all, 59.6% of the athletes had PMS. The PMS group showed higher concentrations of interleukin (IL)-1ß, IL-6, and IL-8 than the athletes without PMS. After the game, IL-6 decreased in the follicular phase and the luteal phase. The tumor necrosis factor-α levels were higher in the group without PMS during the post-game follicular phase than before the game. In the PMS group, tension was higher in the follicular phase before the game and depression was higher in the pre-game luteal phase than in the group without PMS. The PMS group also presented a negative correlation between depression and IL-10 levels in the pre-game follicular phase. Finally, in the pre-game luteal phase were found positive correlations between growth hormone and IL-10. CONCLUSION: PMS influences the inflammatory condition related to mood states and stress hormones in female soccer players.

High urinary interleukin-8 levels is associated with poor prognosis in idiopathic membranous nephropathy.

Biomarkers required to assess accurately the prognosis of idiopathic membranous nephropathy (IMN) are still unavailable. A retrospective study on 156 IMN patients showed only urinary IL-8 was associated with the achievement of initial complete remission (CR) in IMN patients. A urinary IL-8 level of less than 61.25 pg/mL was more sensitive for prediction of CR in IMN patients. Therefore, urinary IL-8 may be a potential biomarker for evaluating short-term prognosis of IMN patients.

Investigating Colorimetric Protein Array Assay Schemes for Detection of Recurrence of Bladder Cancer.

A colorimetric microarray for the multiplexed detection of recurrence of bladder cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular endothelial growth factor (VEGF) was established to enable easy and cheap read-out by a simple office scanner paving the way for quick therapy monitoring at doctors' offices. The chip is based on the principle of a sandwich immunoassay and was optimized prior to multiplexing using IL8 as a model marker. Six different colorimetric assay formats were evaluated using a detection antibody (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III) oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin-carbon, (V) streptavidin (strp)-gold, and (VI) strp-horseradish peroxidase (HRP). Assay Format (III) worked best for NP-based detection and showed a low background while the enzymatic approach, using 3,3',5,5'-tetramethylbenzidine (TMB) substrate, led to the most intense signals with good reproducibility. Both assay formats showed consistent spot morphology as well as detection limits lower than 15 ng/L IL8 and were thus applied for the multiplexed detection of IL8, DCN, and VEGF in synthetic urine. Colorimetric detection in urine (1:3) yields reaction signals and measurement ranges well comparable with detection in the assay buffer, as well as excellent data reproducibility as indicated by the coefficient of variation (CV 5-9%).

[PATHOGENETIC FEATURES OF THE DEVELOPMENT OF OVERACIVE BLADDER IN WOMEN].

The aim of the research was to study the pathogenetic features of the development of the overactive bladder (OAB) in women. 107 women with OAB and a control group of 29 healthy women were involved into the study. The hormonal status was studied based on the determination of serum concentrations of luteinizing hormone (LH), stimulating hormone (FSH), estradiol and progesterone. The urine levels of interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interleukin-8 (IL-8), tumor necrosis factor ά (TNF-ά) and macrophage chemotactic protein-1 (MCP-1) were assessed. Decreased level of estradiol was detected in 26.47% of women of reproductive age. Elevated urine levels of MCP-1 and IL-8 were found in 35.5% of patients. The obtained data testify to the possible pathogenetic role of inflammatory changes in the bladder wall, as well as hypoestrogenism in women of reproductive age in the development of OAB.

High urinary interleukin-2 in late post-transplant period portends a risk of decline in kidney allograft function: a preliminary study.

BACKGROUND: Predictive factors for the rate of decline in kidney allograft function beyond the first post-transplant year have not been thoroughly studied. We aimed to determine whether a single measurement of serum and urinary interleukin 2, interleukin 8 and interleukin 10 at 1-15 years after kidney transplantation could predict a decline in estimated glomerular filtration rate (eGFR) over a 2-year period. RESULTS: Greater serum concentrations of interleukin 8 and interleukin 10 in 30 recipients of kidney allograft at enrollment were associated with lower eGFR after 1 year (beta = - 0.616, p = 0.002 and beta = - 0.393, p = 0.035, respectively), whereas serum concentrations of interleukin 8 also demonstrated significant association with eGFR after 2 years of follow-up (beta = - 0.594, p = 0.003). Higher urinary interleukin 2 concentrations were associated with lower eGFR at baseline (rho = - 0.368, p = 0.049) and after the first (beta = - 0.481, p = 0.008) and the second year (beta = - 0.502, p = 0.006) of follow-up. Higher urinary interleukin 2 concentrations predicted certain decline in eGFR of ≥ 25% from baseline after 1 year of follow-up in logistic regression: odds ratio = 2.94, confidence interval 1.06-8.18, p = 0.038. When combined with time after transplantation, urinary interleukin 2 demonstrated good accuracy in predicting rapid decline in eGFR by > -5 mL/min/1.73 m2/year (area under the receiver-operator characteristic curve: 0.855, confidence interval 0.687-1.000, and p = 0.008). CONCLUSIONS: Our findings suggest that urinary interleukin 2 in the late period after kidney transplantation has promise in identifying patients who are at risk for progressive loss of graft function in a short-time perspective and need closer monitoring.

Development of an interstitial cystitis risk score for bladder permeability.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC) is a multifactorial syndrome of severe pelvic and genitalia pain and compromised urinary function; a subset of IC patients present with Hunner's lesions or ulcers on their bladder walls (UIC). UIC is diagnosed by cystoscopy, which may be quite painful. The objective of this study was to determine if a calculated Bladder Permeability Defect Risk Score (BP-RS) based on non-invasive urinary cytokines could discriminate UIC patients from controls and IC patients without Hunner's ulcers. METHODS: A national crowdsourcing effort targeted IC patients and age-matched controls to provide urine samples. Urinary cytokine levels for GRO, IL-6, and IL-8 were determined using a Luminex assay. RESULTS: We collected 448 urine samples from 46 states consisting of 153 IC patients (147 female, 6 male), of which 54 UIC patients (50 females, 4 male), 159 female controls, and 136 male controls. A defined BP-RS was calculated to classify UIC, or a bladder permeability defect etiology, with 89% validity. CONCLUSIONS: The BP-RS Score quantifies UIC risk, indicative of a bladder permeability defect etiology in a subset of IC patients. The Bladder Permeability Defect Risk Score is the first validated urine biomarker assay for interstitial cystitis/bladder pain syndrome.

The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass: A double-blind randomized controlled trial.

STUDY OBJECTIVE: We attempted to explore the effect of Dex on renal function in patients with cardiac valve replacement under cardiopulmonary bypass (CPB). DESIGN: We designed a prospective, randomized, placebo-controlled, single-center, parallel-arm double-blind trial. SETTING: Operating room. PATIENTS: Seven-two eligible patients were randomly divided into Dex group and placebo group. INTERVENTIONS: Dexmedetomidine (Dex) (0.6µg·kg-1) was administered in patients of Dex group at 15min before anesthesia induction, followed by a treatment of 0.2µg·kg-1·h-1 Dex until the end of operation. Patients in placebo group were treated with normal saline equally. MEASUREMENTS: The levels of serum urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), urine interleukin-8 (IL-18) and superoxide dismutase (SOD) activity were tested before anesthesia induction (T1) and after operation at 0, 12h, 24h and 72h (T2-5). The urine output during operation and the post-operative complication of acute kidney injury (AKI) were recorded. MAIN RESULTS: The levels of BUN and Cr were significantly increased at T5, and similar findings were found in the levels of NGAL and urine IL-18 at T3 and T4. The SOD activity was significantly declined at T2 and T3 in the two groups. The levels of BUN and Cr at T5 and the NGAL level at T3 and T4 were significantly lower in Dex group, comparable to placebo group. The intraoperative urine output was significantly increased and the postoperative incidence of AKI was significantly lower in Dex group. CONCLUSIONS: Dex may attenuate the renal injury and decrease the incidence of AKI in patients undergoing cardiac valve replacement under CPB.

Markers of Intestinal Damage and their Relation to Cytokine Levels in Cardiac Surgery Patients.

OBJECTIVES: In patients undergoing cardiac surgery, both extracorporeal circulation (ECC) and intraoperative mesenterial hypoperfusion may account for increased cytokine levels and lead to postoperative gastrointestinal (GI) symptoms. METHODS: We investigated levels of the intestinal damage markers intestinal fatty acid binding protein (I-FABP in plasma [n = 72] and urine [n = 37]), citrulline (in plasma [n = 35]), and claudin-3 (in urine [n = 37]) in patients undergoing aortic or mitral valve surgery with or without coronary artery bypass grafting. Furthermore, the relationship between these markers and the surgery-induced cytokine response was explored by measuring serial plasma levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 (n = 35). Finally, the relationship between markers of intestinal damage and GI-symptoms (abdominal pain, ileus, vomiting, diarrhea, time to first defecation) was assessed. RESULTS: Plasma and urinary I-FABP levels, and urinary claudin-3 levels peaked at the end of surgery, while citrulline levels were not influenced by surgery. ECC duration correlated with plasma I-FABP levels (r = 0.31, P = 0.007). Plasma levels of all measured cytokines increased during surgery, with peak levels observed either at the end of surgery or on the first postoperative day. While ECC duration correlated with IL-6 and IL-8 release (r = 0.43, P = 0.01 and r = 0.36, P = 0.04 respectively), there was no direct relationship between I-FABP and claudin-3 levels and cytokine concentrations. No patients developed significant GI or non-GI complications, and I-FABP and claudin-3 release appeared not to be related to postoperative GI symptoms, although the incidence of these symptoms may have limited a reliable assessment. CONCLUSIONS: Longer duration of ECC is associated with a more pronounced release of intestinal injury markers and inflammatory cytokines, but intestinal injury markers are not directly related to the observed increase in cytokine levels or GI-symptoms. These findings indicate that ECC duration contributes to the cytokine response observed in cardiac surgery patients and that intestinal injury itself is not a causative factor for this response.

Urinary Levels of IL-1ß and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study.

Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1ß, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1ß and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

Urinary IL-8 is a marker of early and long-term graft function after renal transplantation.

In this study, we examined whether the IL-8 content of urine sampled on day 1 and day 14 after renal transplantation is a marker of early and long-term renal function. Moreover, we assessed whether its concentration is positively correlated with the matrix metalloproteinase-9 (MMP-9) content of urine sampled on day 1 and day 30 and 12 months after renal transplantation. Our analysis covered 87 patients who underwent a kidney transplant. The patients were observed for an average of 30 months (12-60 months). The IL-8 concentration determined on day 1 was significantly negatively correlated with creatinine clearance early after renal transplantation (on days 1, 7, 14 and 30), as well as during long-term observations. IL-8 concentration in urine sampled on day 1 and day 14 was higher in patients demonstrating DGF than in those without DGF. No relationship was found between IL-8 content and cold ischaemia time. MMP-9 activity determined on day 1 and month 3 after renal transplantation was positively correlated with the IL-8 content determined in urine sampled on day 1, Rs = +0.32, p < .05 and Rs = +0.31, p < .05, respectively. The results of this study suggest that a high IL-8 content in urine sampled on day 1 after renal transplantation is an unfavourable marker of early and long-term (years-long) graft function. A high IL-8 content in urine sampled on day 1 after renal transplantation was positively correlated with the activity of metalloproteinase-9 in urine. This proves that both of these chemokines cooperate in ischaemia-reperfusion injuries in transplanted kidneys.