Nerve Growth Factor Levels In Patients Research Articles

Analysis of nerve growth factor (NGF) gene methylation in patients with schizophrenia

Analysis of nerve growth factor (NGF) gene methylation in patients with schizophrenia

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.

Serum level of nerve growth factor is a potential biomarker of conversion to bipolar disorder in women with major depressive disorder

The aim of this study was to identify biomarkers associated with major depressive disorder (MDD) and conversion from MDD to bipolar disorder (BD) in an outpatient sample of women. This was a longitudinal study including women diagnosed with MDD and aged 18 to 60 years. The follow-up was 3 years. The diagnosis was performed using the Mini International Neuropsychiatric Interview Plus. Blood collection was just performed in the first phase. Serum interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and nerve growth factor (NGF) levels were measured using a commercial immunoassay kit. We included 156 women. The conversion rate from MDD to BD was 15.4% (n = 24). NGF serum levels were increased in patients who converted to BD compared to the remitted MDD group and current MDD group (P = 0.013). The Bonferroni post-hoc test for multiple comparisons revealed significant differences for higher NGF levels in patients who converted to BD compared to patients with current MDD (P = 0.037). Interleukin-6, tumor necrosis factor-α, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor serum levels did not differ among the groups. Our results suggest that NGF might be a useful biomarker associated with early detection of conversion to BD, helping clinicians in the clinical diagnosis.

Peripheral blood nerve growth factor levels in major psychiatric disorders

Nerve growth factor (NGF) plays crucial roles in promoting neural growth and survival, and mediating synaptic and morphological plasticity. Several studies investigated the correlation between peripheral NGF levels and major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD); however, the findings were inconsistent. This meta-analysis sought to investigate blood NGF levels in patients with psychiatric disorders compared with healthy subjects and examined potential effects of blood fraction, medication and disease status. A total of 21 eligible studies, encompassing 1342 patients suffering from psychiatric disorders and 1225 healthy subjects, were enrolled in the present meta-analysis. No obvious publication bias was observed either for SCZ, MDD or BPD by the Begg's test (P>0.05). Random-effects meta-analysis showed that SCZ (Z=2.14, P=0.033, SMD=-1.08, 95% CI=-2.07 to-0.09) and MDD (Z=2.57, P=0.010, SMD=-0.61, 95% CI=-1.08 to-0.14) patients had significantly reduced NGF levels, compared with healthy controls. Notably, this decrease was enhanced in un-medicated patients of SCZ (P=0.004) and medicated or chronic patients of MDD (P<0.001). No significant difference of NGF levels was observed between BPD patients and controls (P>0.05). These results supported an association between the reduction of NGF levels and psychiatric disorders. It remains unclear whether the change of NGF levels is a prerequisite for its function in psychiatric disorders development or merely an epiphenomenon unrelated to the pathophysiologic mechanisms.

Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review.

IntroductionSince its discovery several decades ago, nerve growth factor (NGF) has been found to play roles in different areas, such as neurology, endocrinology, and immunology. There is some evidence linking NGF and psychiatry, including the role of NGF in subjects’ response to stress, the alteration of NGF in different emotional states, and the penetration of NGF across the blood–brain barrier under specific conditions. There are many inconsistent findings regarding the differences in NGF in patients with major depressive disorder (MDD) at the present time. The aim of our study was to clarify whether NGF levels are different in MDD compared with healthy controls (HCs).MethodsWe conducted a thorough literature search and compared peripheral NGF levels between MDD and HC through meta-analysis, and investigated possible confounding variables through meta-regression.ResultsSeven studies were brought into the current meta-analysis comparing peripheral NGF in MDD and HCs. The main result was that the NGF levels were significantly lower in MDD than in HCs and that this had an inverse correlation with mean age and disease severity. In addition, meta-analysis of four articles found that the peripheral NGF levels did not change significantly before and after treatment.ConclusionOur study highlights the significant differences in peripheral NGF levels in patients with MDD. However, further exploration of the dynamic changes in peripheral NGF along with the disease course, and specific studies investigating the correlation of NGF in the peripheral and CNS environments are still needed.

Urinary nerve growth factor: a biomarker of detrusor overactivity? A systematic review

Nerve growth factor (NGF) is a signalling protein that interacts with specific receptors in autocrine, paracrine and endocrine modes. It is produced by bladder smooth muscle and urothelium. Patients with overactive bladder and detrusor overactivity (DO) have been found to have increased urinary NGF levels in several small studies. The objective of the review was to assess the accuracy of NGF as a biomarker in the diagnosis of DO by a systematic review of the literature. A systematic search of MEDLINE, Embase, CINAHL, MEDION and LILACS databases was conducted (inception till December 2012). Selection criteria included studies where NGF (as a biomarker for DO) and urodynamics were performed in humans with symptoms of overactive bladder. Two reviewers independently selected articles and extracted data on study characteristics, quality and results. All the eight included studies were of case-control design. A meta-analysis was not performed as there were variations in the quality, methods of performing the NGF assay, different NGF cut-offs used and the format of reporting findings. Two studies used a cut-off of 0.05 for NGF levels. Six studies observed a trend towards higher NGF levels in patients with DO. There was a trend towards higher NGF in patients with DO. However, the data are imprecise and hence cannot be recommended for use in current clinical practice.

Association of Nerve Growth Factor, Chemokine (C-C motif) Ligands and Immunoglobulin E with Pruritus in Cutaneous T-cell Lymphoma

Many patients with cutaneous T-cell lymphoma (CTCL) experience severe pruritus. This study evaluated serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with CTCL. Although serum NGF and BDNF levels in patients with CTCL were not significantly higher than in healthy controls, serum NGF levels in patients with Sézary syndrome were higher than in those with mycosis fungoides and in healthy controls. Enhanced NGF expression by keratinocytes and increased dermal nerve fibres were detected in lesional skin of subjects with Sézary syndrome. Correlations between pruritus in CTCL and serum levels of NGF, BDNF, chemokine (C-C motif) ligand 1 (CCL1), CCL17, CCL26, CCL27, lactate dehydrogenase (LDH), IgE, and soluble interleukin-2 receptor were analysed. Serum CCL1, CCL26, LDH, and IgE levels correlated with pruritus in patients with CTCL. NGF may be associated with increased dermal nerve fibres and pruritus in Sézary syndrome, and CCL1, CCL26, and IgE may be associated with pruritus in CTCL.

Increased serum nerve growth factor levels in patients with overactive bladder syndrome refractory to antimuscarinic therapy

To investigate the serum nerve growth factor (NGF) and urinary NGF levels in patients with overactive bladder syndrome (OAB) refractory to antimuscarinic therapy. Thirty-four patients with OAB (17 OAB-dry and 17 OAB-wet) and 31 normal subjects were enrolled. The patients were diagnosed to have OAB based on symptoms of urgency with/without urgency incontinence and 3-day voiding diary. All OAB patients had been treated with previous antimuscarinic therapy for at least 3 months but had failed. Serum and urine were collected at baseline and after solifenacin treatment for 3 months. The serum NGF and urinary NGF levels were compared between OAB-dry and OAB-wet and between baseline and after solifenacin treatment. Serum NGF levels were significantly elevated in OAB (median and interquartile range, 7.367 pg/ml, 0-57.66) compared to the controls (0.0728 pg/ml, 0-0.234, P < 0.001). Urinary NGF/Cr levels were significantly elevated in patients with OAB (0.685 pg/mg, 0.08-1.94) compared to the controls (0.005 pg/mg, 0-0.0275, P < 0.001). Serum NGF levels were significantly correlated with urinary NGF (P = 0.002) and NGF/Cr levels (P < 0.001) in OAB patients. There was no significant difference of serum NGF levels between OAB-dry and OAB-wet. The serum and urinary NGF levels remained unchanged (P = 0.504 and 0.414, respectively) in OAB patients after solifenacin therapy. The serum NGF levels were highly correlated between baseline and after solifenacin treatment (R(2) = 0.83, P < 0.001). Increased serum and urinary NGF levels in patients with OAB refractory to antimuscarinic treatment suggest these bladder disorders might be caused by chronic inflammation.

Urinary Nerve Growth Factor Levels in Urinary Tract Diseases With or Without Frequency Urgency Symptoms.

To measure urinary nerve growth factor (NGF) levels in patients with several urinary tract diseases under different conditions and compare with NGF levels in patients with overactive bladder (OAB) and interstitial cystitis/painful bladder syndrome (IC/PBS). Urinary NGF levels were measured using enzyme-linked immunosorbent assay (ELISA) and normalized by urinary creatinine concentration. Patients with acute bacterial cystitis, urinary tract stone, urothelial cell carcinoma, and OAB patients after antimuscarinic therapy were evaluated. The urinary NGF levels of OAB, IC/PBS and controls from previous studies were used for comparison. NGF levels were compared among subgroups and between urinary tract diseases with or without associated OAB symptoms. The urinary NGF levels were also compared among natural filling, after normal saline filling and after potassium chloride test in a group of OAB and IC/PBS patients. Patients with acute bacterial cystitis, urinary tract stones or urothelial cell carcinoma had elevated NGF levels that were not associated with the presence of OAB symptoms. Symptomatic cystitis patients who had resolved OAB symptoms after antibiotic treatment had a significant decrease in urinary NGF levels. The urinary NGF levels decreased significantly in OAB patients with effective antimuscarinic treatment for 6 months, but remained stationary and higher than the controls for up to 12 months after treatment. Urinary NGF is not produced solely in patients with OAB or IC/PBS. Acute bacterial cystitis, urinary tract stones and urothelial cell carcinoma can have high urinary NGF production.

Urinary Nerve Growth Factor Levels are Elevated in Patients with Detrusor Overactivity and Decreased in Responders to Detrusor Botulinum Toxin-A Injection

Increased nerve growth factor (NGF) levels have been reported in the bladder tissue and urine of patients with overactive bladder and detrusor overactivity (DO). Determination of urinary NGF level could serve as a valuable biomarker for the diagnosis and monitoring of disease progression of DO. To investigate NGF levels in patients with DO and after treatment including detrusor botulinum toxin A (BoNT-A) injections. A cross-sectional study was performed in a referred center. Participants included 143 patients with idiopathic DO (IDO) and 100 with neurogenic DO (NDO) who were untreated, well-treated, and failed-treated with antimuscarinics. Thirty-eight subjects without lower urinary tract symptoms served as controls. Detrusor injection of BoNT-A (100 U for IDO, 200 U for NDO) was given to 24 patients with IDO and 19 with NDO who had failed antimuscarinic treatment. Urine samples were obtained from controls and patients. Urinary NGF levels were measured by ELISA and normalized by urine creatinine level (NGF/Cr). The urinary NGF/Cr levels in controls and patients with DO at baseline and 3 mo after BoNT-A injection were compared. The mean urinary NGF/Cr levels were significantly higher in 66 patients with untreated IDO (mean+/-standard deviation, 1.44+/-2.66, p=0.000) and 59 with untreated NDO (0.62+/-1.22, p=0.000) compared to controls (0.005+/-0.019). Patients with well-treated IDO or NDO had reduced NGF/Cr levels, whereas those with failed-treated IDO or NDO did not. Patients who responded to BoNT-A treatment had significantly reduced urinary NGF/Cr levels in both the IDO (0.07+/-0.12, p=0.025) and NDO (0.096+/-0.17, p=0.033) groups compared to baseline levels. However, the NGF levels remained significantly higher at 3 mo in 7 IDO (1.01+/-1.25) and 5 NDO (1.64+/-2.39) patients who failed BoNT-A treatment. The major limitation of this study is the wide deviation of the urinary NGF levels and lack of age controls. Urinary NGF level is a sensitive biomarker for the diagnosis of IDO and NDO and can be used as a tool to evaluate the therapeutic effect of detrusor BoNT-A injection.

Urinary Nerve Growth Factor Levels Are Increased in Patients with Bladder Outlet Obstruction with Overactive Bladder Symptoms and Reduced After Successful Medical Treatment

Urinary nerve growth factor (NGF) levels have been shown to be increased in patients with symptoms of overactive bladder (OAB). This study was designed to measure the urinary NGF levels in patients with bladder outlet obstruction (BOO) with or without OAB and to determine whether urinary NGF can serve as a biomarker for OAB. Urinary NGF levels were measured in 38 male control subjects without lower urinary tract symptoms and 153 patients with BOO. The diagnosis of BOO was further classified as BOO/non-OAB (n = 21), BOO/OAB (n = 25), BOO with urodynamically confirmed detrusor overactivity (BOO/DO, n = 47), and BOO/OAB in patients who had received successful medical treatment (n = 60). The urinary NGF levels were measured by enzyme-linked immunosorbent assay and compared among the different groups. The total urinary NGF levels were normalized to the concentration of the urinary creatinine (NGF/Cr) level. The urinary NGF/Cr levels were very low in the control group (mean +/- standard error 0.005 +/- 0.003) and in patients with BOO/non-OAB (0.017 +/- 0.009) and significantly greater in patients with BOO/OAB (0.81 +/- 0.31) and BOO/DO (0.80 +/- 0.13). The urinary NGF/Cr levels were not significantly different between the BOO/OAB and BOO/DO groups; however, the urinary NGF/Cr levels returned to normal levels (0.059 +/- 0.021) after successful relief of OAB symptoms with medical treatment. In our study, patients with BOO/OAB or BOO/DO had significantly greater urinary NGF/Cr levels compared with controls. These levels decreased to normal after successful relief of OAB symptoms. These results suggest that urinary NGF could be a potential biomarker for BOO with symptoms of OAB.

Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder

The origin of overactive bladder (OAB), which is a leading cause of lower urinary tract symptoms, remains unknown. Nerve growth factor (NGF) is one of the neurotrophic factors which are needed for the maintenance of sensory neurons. It is known that too much expression of NGF may induce bladder hyperactivity. In this study, we explored the correlation of the level of urinary NGF with various pathogenic OAB such as idiopathic, neurogenic OAB, and bladder outlet obstruction (BOO). The study group included 51 OAB patients. Thirteen patients (7 females and 6 males) had idiopathic detrusor overactivity (DO) without BOO, 6 female idiopathic OAB without DO (sensory urgency), 16 patients with BOO due to BPH, and 16 patients with neurogenic DO (10 due to spinal cord injury (SCI), 6 due to cerebrovascular disease (CVD)). Thirty-two patients who had normal cystometric findings (23 females and 9 males) without OAB symptoms were used as controls. Urinary NGF levels were measured by enzyme-linked immunosorbent assay technique (ELISA) and the results were normalized based on creatinine (Cr) concentration. The urinary NGF levels in patients with neurogenic DO due to SCI, BOO, and sensory urgency were significantly higher compared with those of normal cystometric finding patients. However, the levels of urinary NGF were not statistically significant between patients with idiopathic DO without BOO, neurogenic DO due to CVD and patients with normal cystometric findings. These data suggest that urinary NGF levels could serve as a basis for adjunct diagnosis of OAB.

Factor de crecimiento nervioso y enfermedades neurológicas

The effects of Nerve Growth Factor (NGF) within and outside the nervous system have been amply discussed in recent decades. Recently clinical studies have shown the effectiveness of this growth factor in the treatment of neurodegenerative disorders. This clinical use makes it necessary to have sensitive, specific methods available to permit measurement of the level of this protein and to determine how it behaves during the course of treatment. To describe the measurement of NGF levels in human serum using an immunoenzymatic method and evaluating the levels of this protein in some neurological disorders. Materials and methods. NGF levels were measured in the serum of healthy persons and in patients with Alzheimer's disease (AD) Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's chorea (HC) using a double site immune-enzymatic assay. Murine 27/21 anti-beta-NGF monoclonal antibody was used as the antibody to cover the plate and as conjugate. Adding a block pass to the method, in which the sample was incubated with an excess of 27/21 antibody effectively reduced the signal observed in the immuno-enzymatic assay. A moderate reduction in beta-NGF levels was seen in the serum of patients with ALS and MS. There was a statistically significant reduction in the patients who were carriers of PD and HC. The significant reduction in NGF levels in patients with PD and HC may be associated with a disorder in the use of this protein in central and peripheral tissues.