Urinary Nerve Growth Factor Research Articles

Acupuncture for overactive bladder in adults: Study protocol for a randomized controlled trial

BackgroundOveractive bladder (OAB) is a prevalent condition that substantially degrades patient quality of life. Acupuncture is recognized as an effective therapeutic approach for various urological diseases. However, there is limited evidence validating the effectiveness and safety of acupuncture for OABs. ObjectiveTo assess the therapeutic efficacy of acupuncture for OAB and to investigate the potential mechanisms by analyzing its effects on relevant urinary biomarkers. MethodsThis is a randomized, participants and outcome assessors blinded, sham acupuncture controlled trial. A total of 110 patients with OABs will be randomly divided in a 1:1 ratio between the acupuncture and sham acupuncture groups. Participants in the acupuncture group will undergo 30-min authentic acupuncture, while their counterparts in the sham acupuncture group will undergo sham acupuncture needling non-acupoints superficially three times weekly for a duration of 8 weeks. The two co-primary outcomes will be the change in the mean number of micturitions per 24 h from baseline to the end of the 8-week treatment and 20-week follow-up. The secondary outcomes will encompass the change in Overactive Bladder Symptom Score, Overactive Bladder Questionnaire Short Form, and average 24 h values of urgency, daytime micturition, nocturia, and mean volume voided per micturition from baseline to weeks 8 and 20. Urinary nerve growth factor, brain-derived neurotrophic factor, and monocyte chemoattractant protein-1 levels will be measured at baseline and week 8. Adverse events will also be documented. DiscussionThe results of this trial provide evidence for the effectiveness and safety of acupuncture in the management of OAB.

Platelet-rich plasma attenuates the UPEC-induced cystitis via inhibiting MMP-2,9 activities and downregulation of NGF and VEGF in Canis Lupus Familiaris model

One of the most prevalent disorders of the urinary system is urinary tract infection, which is mostly brought on by uropathogenic Escherichia coli (UPEC). The objective of this study was to evaluate the regenerative therapeutic and antibacterial efficacy of PRP for induced bacterial cystitis in dogs in comparison to conventional antibiotics. 25 healthy male mongrel dogs were divided into 5 groups (n = 5). Control negative group that received neither induced infection nor treatments. 20 dogs were randomized into 4 groups after two weeks of induction of UPEC cystitis into; Group 1 (control positive; G1) received weekly intravesicular instillation of sodium chloride 0.9%. Group 2 (syst/PRP; G2), treated with both systemic intramuscular antibiotic and weekly intravesicular instillation of PRP; Group 3 (PRP; G3), treated with weekly intravesicular instillation of PRP, and Group 4 (syst; G4) treated with an intramuscular systemic antibiotic. Animals were subjected to weekly clinical, ultrasonographic evaluation, urinary microbiological analysis, and redox status biomarkers estimation. Urinary matrix metalloproteinases (MMP-2, MMP-9) and urinary gene expression for platelet-derived growth factor -B (PDGF-B), nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were measured. At the end of the study, dogs were euthanized, and the bladder tissues were examined macroscopically, histologically, and immunohistochemically for NF-κB P65 and Cox-2. The PRP-treated group showed significant improvement for all the clinical, Doppler parameters, and the urinary redox status (p < 0.05). The urinary MMPs activity was significantly decreased in the PRP-treated group and the expression level of urinary NGF and VEGF were downregulated while PDGFB was significantly upregulated (p < 0.05). Meanwhile, the urinary viable cell count was significantly reduced in all treatments (P < 0.05). Gross examination of bladder tissue showed marked improvement for the PRP-treated group, expressed in the histopathological findings. Immunohistochemical analysis revealed a marked increase in Cox-2 and NF-κB P65 in the PRP-treated group (P < 0.05). autologous CaCl2-activated PRP was able to overcome the bacterial infection, generating an inflammatory environment to overcome the old one and initiate tissue healing. Hence, PRP is a promising alternative therapeutic for UPEC cystitis instead of conventional antibiotics.

Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome.

Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a β3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy. Urinary NGF and BDNFlevels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire. Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05). Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

Urinary biomarkers in children with neurogenic and non-neurogenic lower urinary tract dysfunction: A systematic review and meta-analysis.

The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD). The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program. A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges's g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001). Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD.

Discriminating Different Bladder and Bladder Outlet Dysfunctions by Urinary Biomarkers in Women with Frequency–Urgency Syndrome

To investigate the role of urinary biomarkers in discriminating different bladder and bladder outlet dysfunctions in women with frequency-urgency syndrome. Urine samples collected from 146 women with frequency-urgency syndrome and 34 controls were investigated. All patients were included in previous clinical trials of functional urology studies and underwent a videourodynamic study. Patients with frequency-urgency syndrome were subdivided into idiopathic detrusor overactivity (IDO), neurogenic detrusor overactivity (NDO), dysfunctional voiding (DV), and hypersensitive bladder (HSB) subgroups. Urine samples were collected before any treatment, and urinary inflammatory proteins (interleukin- (IL-) 1β, IL-2, IL-6, IL-8, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor (VEGF)), neurogenic proteins (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin E2 (PGE2)), and oxidative stress biomarkers (8-isoprostane, total antioxidant capacity (TAC), and 8-hydroxydeoxyguanosine (8-OHdG)) were measured and compared between the different OAB subgroups and controls. Of the 146 patients, 31 had IDO, 41 had NDO, 45 had DV, and 29 had HSB. The control group included 34 women. The patients with HSB had lower urinary TAC and IL-2 levels than the controls. The patients with IDO, NDO, and DV had significantly higher urinary TNF-α levels than those with HSB. The patients with IDO and NDO showed an increase in the urinary 8-isoprostane levels, whereas the patients with IDO had higher urinary IL-2, NGF, and BDNF levels than those with NDO. The other urinary inflammatory biomarkers did not show enough significant differences to discriminate between the different bladder and bladder outlet dysfunctions. The urinary levels of inflammatory, neurogenic, and oxidative stress biomarkers varied widely among the patients with bladder and bladder outlet dysfunction. This study's results provide evidence that women with frequency-urgency syndrome and different urodynamic subtypes have varying bladder inflammation and oxidative stress conditions, which might have an impact on treatment outcomes.

Urinary brain-derived neurotrophic factor and nerve growth factor as noninvasive biomarkers of overactive bladder in children.

IntroductionOveractive bladder (OAB) is the most common urinary disorder and the leading cause of functional daytime intermittent urinary incontinence in children. The aim of this study was to determine whether urinary brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) concentrations, normalized to urine creatinine, could be used as biomarkers for diagnosis and treatment monitoring of OAB in children.Materials and methodsUrine samples of 48 pediatric patients with OAB were collected at the start of anticholinergic therapy (baseline), at follow-up visits (3 and 6 months), and from 48 healthy controls. Urinary BDNF and NGF concentrations were determined by ELISA method (Merck, Darmstadt, Germany) and Luminex method (Thermo Fisher Scientific, Waltham, USA). Differences of frequency between quantifiable analyte concentrations between subject groups were determined using Fisher’s exact test.ResultsThere was no statistically significant difference between quantifiable analyte concentrations between patients at baseline and the control group for BDNF and NGF by either the ELISA or Luminex method (P = 1.000, P = 0.170, P = 1.000, and P = N/A, respectively). There was a statistically significant difference between quantifiable BDNF by the ELISA method between patients at baseline and complete success follow-up (P = 0.027), while BDNF by Luminex method and NGF by both methods were not statistically significant (P = 0.078, P = 0.519, and P = N/A, respectively).ConclusionsThis study did not demonstrate that urinary BDNF and NGF concentrations, can be used as biomarkers for diagnosis and therapy monitoring of OAB in children.

Could urinary nerve growth factor and bladder wall thickness predict the treatment outcome of children with overactive bladder?

ABSTRACTObjective:Bladder wall thickness (BWTh) measurements and Nerve Growth Factor (NGF) /creatinine (Cr) values, as noninvasive tools, were found to predict daytime voiding problems in children with overactive bladder (OAB). The goal of this research was to examine if bladder wall thickness together with urine NGF/Cr could be a clinical utility in treatment outcome of OAB in children.Patients and Methods:A total of 60 children with OAB, (Group 1; n=40) and healthy normal controls (Group 2; n=20), aged 6-14 years old were involved in this prospective study. Children were evaluated with detailed history and physical examination, including neurologic examination, and were asked to complete a self-reported questionnaire and a 3-day bladder diary with the aid of their parents. Uroflowmetry was performed in all cases. Urinary nerve growth factor levels were measured by the ELISA and BWTh was measured trans-abdominally by one uro-radiologist specialized in pediatric ultrasonography. Urinary NGF levels were normalized by urinary creatinine levels and compared among all subgroups. Children with OAB received urotherapy as first line treatment at least for three months. 18 children refractory to urotherapy received anticholinergic therapy defined as group 3.Results:The median age of the study group was 10 (range 6 to 16). After urotherapy, 22 children had similar BWTh and NGF/Cr values compared to controls. (2.75 ± 1.15; 2.40 ± 1.00 mm; p=0.86 and 1.02 ± 0.10; 0.78 ± 0.15; p=0.12, respectively). After anticholinergic treatment, BWTh levels (2.25 ± 0.90; 2.40 ± 1.00 mm; p=0.94) and NGF/Cr values (0.95 ± 0.10; 0.78 ± 0.15; p=0.42, respectively) had no significantly difference compared to controls (Group 2).In receiver operating characteristic analysis, bladder wall thickness was found to have sensitivity of 85% and specificity of 84.2% (3,20 AUC, 913; 95 %) and NGF/Cr had sensitivity of 90% and specificity of 92.1% (1,595; AUC, 947; 95 %) in predicting treatment outcome in children with OAB.Conclusions:Bladder wall thickness measurements and NGF/Cr values, as noninvasive tools, could guide outcomes in the treatment of children with overactive bladder.

Plasma and Urinary Levels of Nerve Growth Factor Are Elevated in Primary Hypertension.

Nerve growth factor (NGF) is the main neurotrophic factor that can control sympathetic nerve innervation and sympathetic neural activity in cardiovascular organs. Although NGF overproduction and its influences on the sympathetic nervous system have been shown in hypertensive animals, NGF status and its association with sympathetic nerve activity have not yet been explored in human hypertension. In the present study, therefore, plasma and urinary levels of NGF and those of catecholamines (i.e., indices for NGF status and sympathoadrenal activity, respectively) were compared between 83 untreated primary hypertensives without apparent cardiovascular damages and 81 healthy normotensive subjects. Plasma and urinary levels of NGF were significantly greater in the hypertensive group (311 ± 158 pg/mL and 72.7 ± 54.0 ng/g of Cr) than in the normotensive group (168 ± 188 pg/mL and 54.5 ± 38.8 ng/g of Cr) (p < 0.05 for each measurement), even if the baseline differences of age and gender between the groups were adjusted. Similarly, plasma and urinary levels of catecholamines were significantly higher in the hypertensive group than in the normotensive group except for plasma noradrenaline. In addition, despite no significant correlations between plasma levels of NGF and catecholamines in both groups, urinary NGF significantly correlated positively with both urinary noradrenaline and urinary adrenaline in the hypertensive group (r = 0.259, p=0.018 and r = 0.232, p=0.035), but not in the normotensive group (r = 0.115, p=0.307 and r = −0.018, p=0.871). On the contrary, plasma and urinary levels of NGF as well as those of catecholamines did not associate with any systemic hemodynamic indices such as blood pressure and pulse rate in either group. Thus, primary hypertension was characterized by the enhancements of both NGF status and sympathoadrenal activity and the positive relationship between them. Our data indicate that enhanced NGF status and subsequent NGF-induced sympathoadrenal overactivity could occur in primary hypertension.

Urine Nerve Growth Factor May Not Be Useful as a Biomarker of Overactive Bladder in Patients with Pelvic Organ Prolapse.

(1) Background: Overactive bladder (OAB) symptoms are frequently present in women with pelvic organ prolapse (POP). Although urinary nerve growth factor (NGF) is a promising biomarker of OAB, little is known about its role in patients with OAB secondary to POP. The aim of the study was to evaluate urinary NGF levels in patients with POP involving the anterior vaginal wall and check if it may serve as a predicting factor for postoperative resolution of OAB symptoms. (2) Methods: Eighty-three Caucasian women included in the study were divided into three groups: pure OAB, one associated with POP (POP&OAB) and a control group composed of healthy volunteers. The urine NGF and creatinine were assessed with ELISA tests to calculate the NGF/creatinine ratio. (3) Results: The NGF/creatinine ratio was significantly higher in patients with pure OAB in comparison with other groups; however, it did not differ between the control group and the POP&OAB group. There was no correlation between NGF/creatinine ratio and age, menopausal status, BMI, parity or urodynamic findings. The NGF/creatinine ratio was not a prognostic factor for OAB symptoms’ resolution after surgical treatment of POP. (4) Conclusions: Urinary NGF excretion is not increased in women with OAB secondary to POP; thus, it may not serve as an OAB biomarker in these patients.

The use of urinary biomarkers in the diagnosis of overactive bladder in female patients. A systematic review and meta-analysis.

Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and other proteins are related to overactive bladder (OAB) syndrome, as their urinary concentrations are significantly different from those of the general non-OAB population. This review aims to systematically assess whether NGF, BDNF, and other urinary by-products can be used as potential biomarkers to manage women with OAB. This was a systematic review and metanalysis that was conducted according to PRISMA guidelines. Studies were identified by electronic search of Medline, Scopus, ScienceDirect, Embase, and Cochrane Register until October 2020. The included studies investigated the correlation of OAB with NGF, BDNF, and other potential biomarkers in symptomatic women and their controls. Twelve studies (581 female OAB patients and 394 female controls) were included. Urinary NGF, NGF/Cr, BDNF/Cr, ATP/Cr, and PGE2/Cr ratios were identified as potential biomarkers in female OAB patients. Results of the meta-analysis indicated that uNGF [standard mean difference (SMD) 1.45, 95% CI 0.53-2.36], NGF/Cr ratio (SMD 1.23, 95% CI 0.67-1.78), BDNF/Cr ratio (SMD 0.78, 95% CI 0.006-1.50), and BDNF/Cr ratio (RR 0.78, 95% CI 0.006-1.50) were increased in female OAB patients compared to healthy controls, whereas no difference was found for the PGE2/Cr and ATP/Cr ratios. Current data are inadequate to assess any other potential biomarkers, such as urinary MDA, ATP, and cytokines, in the management of OAB in female patients. uNGF, NGF/Cr, and BDNF/Cr ratio could be used in the assessment of female OAB patients. Further studies are needed to specify OAB urinary titer levels in OAB subgroups and healthy women and their potential as diagnostic and management tools in OAB women.

Üriner Sistem Semptomları Olan Multipl Sklerozlu Hastalarda Üriner Sinir Büyüme Faktörü Düzeyleri

Aim: To estimate the sensitivity and specificity of the serum and urinary nerve growth factor (NGF) in MS patients as markers of detrusor overactivity. &#x0D; Materials and Methods: 20 volunteers who were diagnosed with MS and who had urinary tract symptoms and 29 volunteers who were diagnosed with MS however who did not have urinary tract symptoms were included in the study. A comprehensive anamnesis and spot urine samples were obtained from the subjects. Twenty seven healthy volunteers with similar age and gender distribution were included for making a comparison with regard to NGF levels and spot urine samples were obtained.&#x0D; Results: Urinary NGF levels and NGF/urinary creatinine ratios were found lower in the group composed of MS patients who had urinary symptoms compared to the group composed of MS patients who did not have urinary symptoms but the difference was not statistically significant. These parameters were found lower in patient group who did not have urinary symptoms compared to control group however the difference was not statistically significant (p: 0,114 and 0,833)&#x0D; Conclusions: urinary neurotrophins in patients with multiple sclerosis can be used to diagnose detrusor overactivity.

Correlation between the NGF levels and questionnaire forms in patients receiving antimuscarinic treatment and those receiving onabotulinum toxin-A injection.

To compare nerve growth factor (NGF) levels in patients who received antimuscarinic, versus onabotulinum toxin-A (onaBoNT-A) injection, as well as to investigate whether there is a correlation between NGF levels, and 8-item overactive bladder questionnaire(OAB-V8), urogenital distress inventory (UDI)-6, and incontinence impact questionnaire (IIQ)-7 forms. Fourty adult patients with OAB were enrolled in this prospective study. An antimuscarinic was prescribed to 20 naive patients, and onaBoNT-A injection was administered to 20 patients, who were refractory to antimuscarinics. Urine samples were obtained before, and after 3rd and 6th months of treatment, and NGF levels were measured. Symptom scores of OAB-V8, UDI-6,and IIQ-7 were recorded. There was no significant difference between groups in terms of the initial OAB-V8, IIQ-7, and UDI-6 scores, whereas NGF values showed no significant difference over time in onaBoNT-A group (p=0.069, p=0.069). NGF levels were significantly lower in 3rd and 6th months, in patients receiving antimuscarinic (p=0.003, p=0.007); a strong correlation was found in 3rd month between the NGF levels, OAB-V8 scores (r=0.704, p=0.001), and IIQ-7 scores (r=0.676, p=0.001), and a moderate correlation between NGF levels, and UDI-6 scores (r=0.583, p=0.007). In the 6th months, a very strong correlation was found between NGF levels, and OAB-V8 scores (r=0.811, p=0.004), and a strong correlation was found between NGF levels, and IIQ-7 scores (r=0.671, p=0.001). In onaBoNT-A group, there was no significant correlation between NGF levels, and other variables. NGF level might be a good marker to evaluate effectiveness of treatment in patients receiving antimuscarinics, owing to correlation of urinary NGF levels with symptom scores. Lack of correlation in patients receiving onaBoNT-A injection could be a result of differences in the mechanism of action.

Relationship of potential biomarkers of interstitial cystitis/painful bladder syndrome

BACKGROUND: Biomarker identification fulfills the need for simple, accurate, and non-invasive diagnostic methods for interstitial cystitis/painful bladder syndrome (IC/PBS). The simultaneous study of cytokines and growth factors is essential for understanding the role of biomarkers.&#x0D; AIM: This work determines the concentration of interleukins (IL) 6 and 8, nerve growth factor (NGF), heparin-binding epidermal growth factor (HB-EGF), and their relationship in patients with IC/PBS.&#x0D; MATERIALS AND METHODS: This study examined 126 female patients with IC/PBS, with a mean age of 46.714.0 years. The disease duration averaged 6.02.8 years. The control group consisted of 20 women without IC/PBS, with a mean age of 35.39.7 years. The level of IL-6 and IL-8 in blood serum and urine was determined by ELISA. The NGF and HB-EGF levels were determined by ELISA using the appropriate test kits. Statistical analysis was performed using SPSS software version 15.0. The Students t-test and Spearmans correlation coefficient were calculated.&#x0D; RESULTS: In patients with IC/PBS, blood levels of IL-6 and IL-8 exceeded the control indicator by 65.99% (t=4.62, p=0.000) and by 67.14% (t=2.81, p=0.006), respectively, the NGF level exceeded it by 8.82% (t=0.10, p=0.920), and the HB-EGF level decreased by 30.84% (t=0.62, p=0.537). In urine, the level of IL-6 in IC/PBS was increased by 52.94% (t=7.62, p=0.000), IL-8 level was increased by 57.53% (t=2.01, p=0.049), NGF was increased by 50.44% (t=2.06, p=0.043), and HB-EGF level was increased by 56.44% (t=2.01, p=0.049). Cytokines correlated with growth factors with weakly bound in blood and urine (p 0.05). A strong, direct relationship was registered between the urine levels of NGF and HB-EGF (r=+0.987, p 0.05).&#x0D; CONCLUSIONS: Correlations between IL-6 and IL-8 with NGF and HB-EGF in urine indicate an increased risk of damage to the bladder epithelium. The increase in urinary HB-EGF is a response to a significant increase in urinary NGF and may be a bladder epithelial defense mechanism.

Diagnostic value of nerve growth factor in detrusor overactivity: a study on women with mixed urinary incontinence.

Urinary incontinence has a profound impact on women's quality of life. Studies have shown that changes in urinary protein levels could be a potential diagnostic biomarker in some urological diseases. The aim of present study is to determine the diagnostic value of nerve growth factor (NGF) in women with mixed urinary incontinence (MUI) as a diagnostic biomarkers of detrusor overactivity (DO). Seventy women aged between 20 and 75years with MUI were enrolled in this prospective study. All participants underwent urodynamic study. Urine NGF levels were measured using an ELISA method. NGF level was compared between groups using Mann-Whitney U test. Receiver Operator Characteristic (ROC) analysis was employed to evaluate the diagnostic performance of urinary NGF. The results showed that the median (min, max) of NGF in patients with DO was significantly higher in comparing to its level in women without DO [184.10 (31, 346.60) pg/ml vs. 151.80 (21, 210.70)], respectively (P = 0.035). Using receiver-operator characteristics analysis, the threshold urinary NGF value of 102.00pg/ml provided a sensitivity of 88% and specificity of 40% in diagnosing DO, PPV of 39.1%, and NPV of 88.2%, positive likelihood ratio 2.18 and negative likelihood ratio of 0.45 (P = 0.02). Based on high sensitivity and low specificity, we can conclude that NGF can be a good tool for ruling out the OAB when the test is negative. However, the future investigations are needed to expand the observed correlation in larger groups of women with DO.

Urinary Nerve Growth Factor in full-term, preterm and intra uterine growth restriction neonates: Association with brain growth at 30–40 days of postnatal period and with neuro-development outcome at two years. A pilot study

Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30−40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30−40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.

Impact of intradetrusor botulinum toxin A injections on serum and urinary concentrations of nerve growth factor and brain-derived neurotrophic factor in patients with multiple sclerosis and neurogenic detrusor overactivity.

To evaluate the practical relevance of changes in serum and urinary neurotrophins levels in patients with multiple sclerosis (MS) and neurogenic lower urinary tract dysfunction (NLUTD) after intradetrusor injections of botulinum toxin A (BoNTA). The study included 36 patients with MS and NLUTD and 20 controls. The patients with NLUTD received intradetrusor injection of BoNTA (200 U). The nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels were measured in serum and urine at baseline and then at 1, 3, and 6 months by enzyme-linked immunosorbent assay. Urinary NGF and BDNF were normalized to creatinine (NGF/Cr, BDNF/Cr). Patients' assessment included urodynamic examination and Neurogenic Bladder Symptom Score (NBSS). After BoNTA injections, no significant changes were observed in the serum NGF and BDNF or the urinary BDNF/Cr. The urinary NGF/Cr was significantly higher in MS patients (1.23 ± 0.34) at baseline compared with controls (0.084 ± 0.02; p = .021). The urinary NGF/Cr decreased to 0.51 ± 0.12 (p = .001) and 0.53 ± 0.32 (p = .005) at 1 and 3 months, increasing to 1.12 ± 0.49 (p = .003) at 6 months. The urinary NGF/Cr level at baseline demonstrated a low diagnostic accuracy in predicting a better response to the BoNTA treatment (area under the curve = 0.661; p = .047) and no correlation with the urodynamic parameters. The urinary NGF/Cr at baseline or its reduction at the first month following treatment does not serve as a predictor for the response to the BoNTA injections or for urodynamic changes.

Genetic variants and expression changes in urgency urinary incontinence: A systematic review.

AimTo perform a systematic review summarizing the knowledge of genetic variants, gene, and protein expression changes in humans and animals associated with urgency urinary incontinence (UUI) and to provide an overview of the known molecular mechanisms related to UUI.MethodsA systematic search was performed on March 2, 2020, in PubMed, Embase, Web of Science, and the Cochrane library. Retrieved studies were screened for eligibility. The risk of bias was assessed using the ROBINS‐I (human) and SYRCLE (animal) tool. Data were presented in a structured manner and in the case of greater than five studies on a homogeneous outcome, a meta‐analysis was performed.ResultsAltogether, a total of 10,785 records were screened of which 37 studies met the inclusion criteria. Notably, 24/37 studies scored medium‐high to high on risk of bias, affecting the value of the included studies. The analysis of 70 unique genes and proteins and three genome‐wide association studies showed that specific signal transduction pathways and inflammation are associated with UUI. A meta‐analysis on the predictive value of urinary nerve growth factor (NGF) levels showed that increased urinary NGF levels correlate with UUI.ConclusionThe collective evidence showed the involvement of two molecular mechanisms (signal transduction and inflammation) and NGF in UUI, enhancing our understanding of the pathophysiology of UUI. Unfortunately, the risk of bias was medium‐high to high for most studies and the value of many observations remains unclear. Future studies should focus on elucidating how deficits in the two identified molecular mechanisms contribute to UUI and should avoid bias.

Оценка взаимодействия фактора роста нервов и тучных клеток при интерстициальном цистите/синдроме болезненного мочевого пузыря в эксперименте

to evaluate the level of nerve growth factor (NGF) in the blood and urine and mast cell infiltration of the bladder wall in a model of interstitial cystitis/bladder pain syndrome (IC/BPS) and to analyze their relationships. IC/BPS modeling was performed on 38 female rabbits, which were divided into 4 groups. In the group 1, IC/BPS was simulated by an instillation of 70% alcohol into the bladder, while in group 2 and 3 animals own urine and normal saline were injected into the bladder wall. The group 4 consisted of intact animals. The NGF level was determined by ELISA. To determine the concentration of mast cell in tissues, each cross-section was divided into 10 sections. The severity of mast cell infiltration was evaluated in each area using the following scale: 0 - no mast cells; 1 - less than 20 cells; 2 - 20-45 cells; 3 - more than 45 cells. The points of all 10 areas were added up, divided by 30 (the maximum possible score) and multiplied by 100. An increase in the NGF level in the blood and urine was seen in different models of IC/BPS, but it was significantly more pronounced in the group 2 (toxic model). Mast cells were determined only in the group 1 (0.25+/-0.707) and 2 (14,200+/-5,796). In animals with the urinary toxicity model, mast cell activity was significantly higher in comparison with those in the model with an instillation of 70% alcohol (p<0.001). The level of NGF in blood and urine correlated in different directions. Mast cell proliferation and activation was determined in case of impairment of the bladder wall integrity by the injection of urine. Our animal model of IC/BPS, which was created by instillation of 70% alcohol into the bladder and the injection of urine into the bladder wall, showed an increase in the level of NGF in urine and blood and the concentration of mast cells. These findings, as well as relationship between these values indicate the development of neuroimmune inflammation in this pathological condition. Considering the involvement of many factors in the pathogenesis of this syndrome, further researches are required.

Partners in Crime: NGF and BDNF in Visceral Dysfunction.

Neurotrophins (NTs), particularly Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), have attracted increasing attention in the context of visceral function for some years. Here, we examined the current literature and presented a thorough review of the subject.After initial studies linking of NGF to cystitis, it is now well-established that this neurotrophin (NT) is a key modulator of bladder pathologies, including Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS. NGF is upregulated in bladder tissue and its blockade results in major improvements on urodynamic parameters and pain. Further studies expanded showed that NGF is also an intervenient in other visceral dysfunctions such as endometriosis and Irritable Bowel Syndrome (IBS).More recently, BDNF was also shown to play an important role in the same visceral dysfunctions, suggesting that both NTs are determinant factors in visceral pathophysiological mechanisms. Manipulation of NGF and BDNF improves visceral function and reduce pain, suggesting that clinical modulation of these NTs may be important; however, much is still to be investigated before this step is taken.Another active area of research is centered on urinary NGF and BDNF. Several studies show that both NTs can be found in the urine of patients with visceral dysfunction in much higher concentration than in healthy individuals, suggesting that they could be used as potential biomarkers. However, there are still technical difficulties to be overcome, including the lack of a large multicentre placebo-controlled studies to prove the relevance of urinary NTs as clinical biomarkers.

Effect of Water Avoidance Stress on serum and urinary NGF levels in rats: diagnostic and therapeutic implications for BPS/IC patients

Nerve growth factor (NGF) is thought to play a key role in chronic pain felt by bladder pain syndrome/interstitial cystitis (BPS/IC) patients by activating its high affinity receptor tropomyosin-related kinase subtype A (Trk A). Whether this pathway is also involved in the aggravation of pain sensation during stress events was here investigated. The levels of plasmatic NGF were increased in rats submitted to Water Avoidance Stress test (WAS), compared to controls. The administration of the alpha1A adrenoceptors blocker silodosin prevented the increase of plasmatic NGF. Urinary NGF levels were also moderately increased in animals submitted to WAS. WAS increased pain behaviour score, lowered abdominal mechanical pain threshold and increase voiding bladder reflex activity. These changes were prevented by the administration of TrkA antagonist GW441756. These findings prompt the use of plasmatic NGF as diagnosis tool for chronic visceral painful conditions and opens therapeutic opportunities for TrkA receptors antagonist/NGF sequestration.