Serum Neopterin Concentrations Research Articles

P23 The influence of maternal inflammatory status on the risk of atopic eczema in offspring during infancy

Abstract Introduction and aims Maternal influences on infantile atopic eczema are complex, with emerging evidence for a protective role for maternal T helper (Th)1 inflammation during pregnancy. Substantial literature on characterization of a proinflammatory dietary pattern, led us to hypothesize that analyses of maternal diet and markers of inflammation might help identify mechanisms influencing the risk of infantile atopic eczema. The aim of this study was to examine the associations between energy-adjusted dietary inflammatory index (eDII) scores indicative of a proinflammatory diet pattern, maternal serum neopterin levels (a biomarker elevated in Th1 immune activation which counteracts Th2 inflammation seen in atopic eczema), and infantile risk of atopic eczema. Methods Within the UK Southampton Women’s Survey, scores for the eDII were derived from mothers’ diets (questionnaires at preconception, early and late pregnancy). Atopic eczema was ascertained at age 6 and 12 months using the UK Working Party Diagnostic Criteria (n = 262 and 270, respectively). Late pregnancy maternal serum neopterin levels were measured in a subsample (n = 497). Directed acyclic graphs were used to determine covariates to be included in linear regression analyses. Results A higher eDII score in late pregnancy was associated with a reduced risk of atopic eczema at age 6 months [odd ratios (OR) 0.89, 95% CI confidence interval (CI) 0.81–0.98; P = 0.02], with a similar trend at age 12 months (OR 0.91, 95% CI 0.83–1.00; P = 0.06). Consistent with this, and adjusting for maternal body mass index, education, smoking during pregnancy, and recent eczema, and infant filaggrin single-nucleotide polymorphism rs7512552, breastfeeding duration and sex, higher maternal serum concentrations of neopterin were associated with lower risks of infant eczema at age 6 months (OR 0.72, 95% CI 0.51–1.01; P = 0.05) and 12 months (OR 0.71, 95% CI 0.53–0.96; P = 0.03). Conclusions These findings suggest that a proinflammatory maternal diet that promotes a Th1 predominant environment protects the developing infant from Th2 inflammation and reduces the risk of atopic eczema.

The concentration of serum neopterin in patients with surgical treatment of spondyloarthrosis complicated byfacet syndrome

Objective. To study the concentration of serum neopterin in patients before and after surgical treatment of pain syndrome caused by the formation of facet syndrome associated with spondyloarthrosis.
 Materials and methods. The study involved 52 patients (32 men and 20 women) hospitalized to the neurosurgical department of the City Clinical Hospital No. 4. The main group consisted of 26 patients with spondyloarthrosis complicated by chronic pain associated with facet syndrome. The comparison group (n=26) consisted of patients with pain syndrome in radiculopathy. The control group (comparable in gender and age) consisted of 10 people who underwent periodic examination. The concentration of neopterin in blood serum was determined by solid-phase enzyme immunoassay (ELISA) using the Neopterin ELISA kit (cat. No. 59321; lot ENO230) ("IBL", Germany).
 Results. Statistically significant differences in the level of serum neopterin concentration (p = 0.0016) were revealed between the studied groups. The highest concentration of neopterin was noted in the comparison group, where it was 10.31 ± 2.02 nmol/l, exceeding the results of the control group (p=0.02256) and the main group (p=0.04996). Three months after surgical treatment of patients in the main group, the median content of serum neopterin decreased by 1.161 times (p = 0.049029).
 Conclusion. Further studies to clarify the influence of pain on metabolic processes and neopterin in particular are required.

Biological variation of serum neopterin concentrations in apparently healthy individuals.

The aims of this study were to determine the biological variation (BV), reference change value (RCV), index of individuality (II), and quality specifications for serum neopterin concentrations; a measurand provided by clinical laboratories as an indicator of cellular immunity. The study delivered serum samples collected for 10 consecutive weeks from 12 apparently healthy individuals (3 male, 9 female). Serum neopterin concentrations were measured using high-performance liquid chromatography with fluorometric detection. The data analysis was performed using an online statistical tool and addressed published criteria for estimation of biological variation. The mean neopterin concentration was 5.26 nmol/L. The within-subject biological variation (CVI) with 95 % confidence interval (CI) of neopterin serum concentrations was 11.54 % (9.98-13.59), and the between-subject biological variation (CVG) with 95 % CI was 43.27 % (30.52-73.67). The neopterin asymmetrical RCV was-24.9 %/+33.1 %, and the II was 0.27. The desirable quality specifications for neopterin were <5.77 % for precision, <11.20 % for bias, and <20.72 % for total allowable error (TEa). When analytical variation was used instead of CVI to calculate TEa, the desirable TEa was <18.39. This study determined BV data for neopterin, an indicator of cell-mediated immune response. Asymmetric RCV values, of 24.9 % decrease or a 33.1 % increase between consecutive measurements indicate significant change. The II of 0.27 indicates a high degree of individuality, therefore that it is appropriate to consider the use of personal reference data and significance of change rather than the reference interval as points of reference for the evaluation of neopterin serum concentrations.

Association of angiotensin-converting enzyme (ACE) I/D variation with biochemical parameters and oxidative stress markers in systemic lupus erythematosus patients in west of Iran.

We aimed to study insertion/deletion (I/D) variation (rs4646994) of ACE gene in a group of SLE patients in west of Iran and its possible relationship with oxidative stress. Genotypes and allele frequencies related to ACE (I/D) variation were determined in 108 SLE patients and 110 gender and age-matched healthy controls using PCR. Neopterin, malondialdehyde (MDA), and serum lipid concentrations were determined by HPLC and enzyme assay respectively. The overall distribution of ACE I/D genotypes in SLE patients was different from that of the control group (P = 0.005). DD genotype compared to ID genotype increased the risk of SLE (OR = 2.57, 95% CI 1.4-4.8, P = 0.003). ID genotype compared to the II genotype decreased the risk of disease (OR = 0.45, 95% CI 0.2-0.99, p = 0.042). SLE patients with DD, ID, and II genotypes had lower paraoxonase (PON) activity and higher serum levels of MDA and neopterin versus control patients. We also detected a significant protective effect against SLE in presence of ACE I alleles and lack of angiotensin II receptor, type 1 (AGTR1) A1166C (NCBI reference SNP id: rs5186), C alleles in this study (OR = 0.31, 95% CI 0.14-0.68, P = 0.002). Carriers of the DD genotype of ACE gene with higher serum concentrations of neopterin and MDA, and lower PON activity had a high risk to develop SLE, while ID genotype decreased the risk of disease development by 2.22 times compared to II genotype.

#4277 EGF, GDF-15 AND NEOPTERIN AS PREDICTORS OF CHRONIC KIDNEY DISEASE PROGRESSION IN CHILDREN BY MEANS OF ARTIFICIAL NEURAL NETWORK MODELS

Abstract Background and Aims Progression of chronic kidney disease (CKD) is a compound process, where activation of immunocompetent cells and subclinical inflammation play pivotal role. Enhanced atrophy of the tubular cells, and finally, gradual fibrosis of tubulointerstitial tissue, are responsible for irreversible character of the disease. Multiple molecules influence above-mentioned processes. Growth differentiation factor (GDF)15, a member of TGF-β cytokine superfamily, is a marker of inflammation and an integrative signal in both acute and chronic stress conditions. Elevated serum concentrations of GDF15 were associated with increased risk of development and progression of CKD in adults, as well as with mortality in this group of patients. Our previous investigation revealed increased serum GDF15 concentrations in children on chronic dialysis. Epidermal growth factor (EGF), a tubule-specific protein, promotes proliferation, differentiation and migration of epithelial cells, and therefore, modulates regeneration of injured renal tubules. Decreased concentrations of EGF in urine were observed in variety of kidney diseases, including diabetic nephropathy, lupus nephritis or CKD. Our previous analysis of EGF serum concentrations in CKD children confirmed their decreased values on chronic dialysis. Neopterin is a product of activated monocytes and macrophages and serves as a marker of cell-mediated immunity. Elevated serum concentrations of neopterin were observed in CKD adult patients, our investigation revealed its increased values in children on chronic dialysis. None of the above mentioned markers was analyzed in the population of CKD children treated conservatively. Therefore, the aim of study was to assess the serum concentrations of EGF, GDF-15 and neopterin in children with CKD on conservative treatment and verify the usefulness of these markers in predicting CKD progression by means of artificial intelligence tools. Method The study group consisted of 153 children with pre-dialysis CKD stages 1-5 (stage 1 – 27 patients, stage 2 – 26 patients, stage 3 – 51 patients, stage 4 - 28 patients, stage 5 – 21 patients). EGF, GDF-15 and neopterin serum concentrations were assessed by ELISA. The patient database was implemented into the artificial neural network. In detail, the recursively selected subsets of input variables constituted the input layer of an artificial neural network built of perceptrons (multi-layer perceptron). Anthropometric data, biochemical parameters, EGF, GDF15 and neopterin were included into the model, serum creatinine and eGFR, as direct classifiers of CKD stage, were excluded. Various models were tested, regarding their accuracy, AUROC and Matthews correlation coefficient (MCC) values. Results EGF serum concentrations decreased gradually, whereas GDF15 and neopterin values rose systematically with CKD progression, keeping statistically significant inter-stage differences. Moreover, the most precise ANN model, among the tested artificial neural networks, contained EGF, GDF15 and neopterin as input parameters and classified patients into either CKD 1-3 or CKD 4-5 groups. This model has put new patients into appropriate classes with excellent Accuracy of 96.77%, AUROC 0.9169 and Matthews correlation coefficient (MCC) of 0.9157. Conclusion The presented model of an artificial neural network, with serum concentrations of EGF, GDF15 and neopterin as input parameters, may serve as a useful predictor of CKD progression in the pediatric population. It suggests the essential role of inflammatory processes, defined by newly discovered markers, in the renal function decline towards advanced stages of CKD in children.

Residual Central Nervous System Immune Activation Is Not Prevented by Antiretroviral Therapy Initiated During Early Chronic HIV Infection.

Antiretroviral therapy (ART) initiated during acute infection can potentially impact the central nervous system (CNS) reservoir, but the differential long-term effects of ART initiation during early or late chronic infection are unknown. We included neuroasymptomatic people with human immunodeficiency virus (HIV) with suppressive ART initiated during chronic (>1 year since transmission) HIV with archived cerebrospinal fluid (CSF) and serum samples after 1 and/or ≥3 years of ART from a cohort study. CSF and serum neopterin was measured using a commercial immunoassay (BRAHMS, Germany). In total, 185 people with HIV (median, 79 [interquartile range, 55-128] months on ART) were included. A significant inverse correlation was found between CD4+ T-cell count and CSF neopterin only at baseline (r = -0.28, P = .002), but not after 1 (r = -0.026, P = .8) or ≥3 (r -0.063, P = .5) years of ART. No significant differences were seen in CSF or serum neopterin concentrations between different pretreatment CD4+ T-cell strata after 1 or ≥3 (median, 6.6) years of ART. In people with HIV initiating ART during chronic infection, occurrence of residual CNS immune activation was not correlated with pretreatment immune status, even when treatment was initiated at high CD4+ T-cell counts, suggesting that the CNS reservoir, once established, is not differentially affected by the timing of ART initiation during chronic infection.

Dynamika klinichnykh oznak i pokaznykiv biomarkera zapalennia neopterynu v syrovattsi krovy krolykiv iz eksperymentalnym neinfektsiinym avtoimunnym uveitom, z urakhuvanniam riznoho stupenia tiazhkosty

Introduction. Uveitis is an inflammatory condition involving iris, ciliary body and choroid of the eyebulb. Uveitis curretntly affects about two million people worldwide and is among five leading causes of blindness in the working population. Diagnosis of uveitis requires a number of investigations. As important biomarker in the diagnosis of uveitis can be used the detection of Neopterin (NP) in blood serum, since it is a stable metabolite and its increased level encompass activation of cellular immunity. It should be also noted that NP is present in blood serum and plasma, urine, tears, aqueous humor, vitreous body, other biological fluids and can be easily detected. According to literature data and our own investigations, the concentration of NP usually depends on the degree of activity of the pathological process, and its high concentration of NP is one of the main predictors of an unfavorable prognosis. The aim of the study. To investigate the dynamics of clinical signs and inflammatory biomarker Neopterin level in blood serum of rabbits with experimental non-infectious autoimmune uveitis (NAU) considering varying degrees of severity. Materials and methods. The experimental study was conducted on 30 rabbits of the “Chinchilla” breed, which were divided into two main groups (I and II), 15 animals in each. NAU was induced by intravitreal injection of an undiluted normal sterile horse serum to group I rabbits, while group II animals received diluted with the physiological solution serum in the proportion of 1:2. General sensitization was previously carried out with the same serum injected intravenously. Results. The average level of NP in rabbits before the start of the experiment was 1.7 ± 0.2 nmol/l. It was considered the norm, since there is no information in the literature about the study of NP in healthy rabbits of the “Chinchilla” breed. In the reported research the severity of experimental NAU was estimated due to the concentration of the injected normal sterile horse serum intravitreally. As an additional proof of the development of NAU clinical picture was used the detection of Neopterin concentration in blood serum of rabbits. In both group animals the development of acute inflammation on days 3, 7, 10 and 14 of experiment the NP level was significantly higher compared to control (p-value less than 0.05). However, in the I group animals with moderate and severe NAU, the level of NP was significantly higher than that in group II, in which uveitis was characterized by a mild course. Namely, on the 3rd day of experiment NP concentration in the I group animals was 5.60 ± 0.70 nmol/l, in the group II – 4.70 ± 0.60 nmol/l (p-value less than 0.05); on day 7th – 6.00 ± 0.20 nmol/l and 4.45 ± 0.30 nmol/l (p-value less than 0.05); on day 10th – 5.90 ± 0.40 nmol/l and 2.60 ± 0.40 nmol/l (p-value less than 0.05); on the 14th – 3.80 ± 0.40 nmol/l and 2.10 ± 0.10 nmol/l (p-value less than 0.05). On the day 21st, the NP concentration in both group animals did not differ statistically – estimated level 2.70 ± 0,30 nmol/l, (p-value more than 0.05) – which apparently encompass the regression of inflammatory changes in the eye. Conclusions. A correlation between the severity of experimental non-infectious autoimmune uveitis with concentration of inflammatory biomarker neopterin in blood serum was investigated in rabbits. NP level in all experimental animals was elevated and statistically different in comparison to NP control levels on days 3rd, 7th, 10th and 14th day of experiment. In the group of animals with a more severe course of uveitis, a significantly higher level of NP was noted compared to animals with a milder course of NAU. This observation confirms the immune response to inflammation and the stability of NP biomarker in blood serum. The dynamics of this biomarker levels in rabbits of two experimental groups has a correlation with the dynamics of clinical changes. Detection of the inflammatory biomarker Neopterinin in blood serum can be used as a criterion for assessement the severity of non-infectious autoimmune uveitis, its course and, probably, prognosis.

Pharmacokinetics/pharmacodynamics by race: Analysis of a peginterferon β-1a phase 1 study

Black/African American participants are underrepresented in clinical trials for multiple sclerosis but can experience a greater burden of disease than other racial groups in the United States. A phase 1, open-label, crossover study that demonstrated bioequivalence of subcutaneous and intramuscular injection of peginterferon β-1a in healthy volunteers enrolled similar proportions of Black and White participants, enabling a post hoc subgroup analysis comparing these groups. Peginterferon β-1a (125μg) was administered by subcutaneous or intramuscular injection, followed by a washout period before a second injection using the alternative method. The primary pharmacokinetic and pharmacodynamic endpoints were maximum observed concentration (Cmax) and area under the concentration-time curve from hour 0 to infinity (AUCinf) of study drug and serum concentration of neop-terin, respectively. Safety and tolerability were included as secondary endpoints. This analysis included 70 (51.5%) Black and 59 (43.3%) White participants. Peginterferon β-1a Cmax was 29.8% higher in Black than in White participants following subcutaneous administration but was similar following intramuscular administration. Mean AUCinf was 31.0% and 11.8% greater in Black than in White participants with subcutaneous and intramuscular administration, respectively. Pharmacodynamics and safety signals were similar between groups, although Black participants reported numerically fewer adverse events. No clinically meaningful differences were identified between Black and White participants related to peginterferon β-1a administration, supporting the approved dose of 125μg/mL peginterferon β-1a. Future clinical studies should include sufficiently diverse populations to ensure accurate assessments of treatment response. Funding for medical writing support was provided by Biogen (Cambridge, MA, USA).

Assessment of serum neopterin and kynurenine levels in Egyptian children with sickle cell disease: a single center study

Neopterin, a guanosine triphosphate metabolite, is an indicator for cell-mediated immunity. Kynurenine performs a variety of biological functions, such as the dilation of blood vessels in response to inflammation and the regulation of immune response. Objectives: to assess serum neopterin and kynurenine levels in Egyptian children with sickle cell disease (SCD). In our case-control study, we included 40 children aged 2–18 years with SCD treated at the Hematology Unit of the Department of Pediatrics, Menoufia University Hospital and 40 healthy controls matched on age, sex, and socio-economic status. The study was approved by the Institutional Review Board (IRB) of the Menoufia Faculty of Medicine. We obtained comprehensive health history data of the study participants and performed necessary clinical examinations and tests including complete blood count, serum ferritin, and hemoglobin electrophoresis. Serum neopterin and kynurenine concentrations were measured using enzyme-linked immunosorbent assay. In the patients with SCD, serum neopterin and kynurenine levels were significantly higher during vaso-occlusive crisis than in a steady state, and much higher than in the controls (p &lt; 0.001). There was a significant positive correlation between serum neopterin concentrations and mean corpuscular hemoglobin levels, platelets, HbF, HbS, and HbA2, and a significant negative correlation between serum neopterin levels and height, Hb, hematocrit and HbA1. We also observed a significant positive correlation between serum kynurenine and body mass index, HbA2, HbF, HbS, and platelets and a significant negative correlation between serum kynurenine and hemoglobin, hematocrit and HbA1. The cases were shown to have higher neopterin and kynurenine levels than the controls. The concentrations of neopterin and kynurenine were higher in the patients during vaso-occlusive crises than in a steady state.

Urine neopterin in childhood acute demyelinating diseases: Potential for differential diagnosis

Inflammatory demyelinating diseases of the central nervous system (CNS) in childhood include clinically and radiologically defined diseases such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Differentiation between these phenotypes can be difficult and cases not meeting established diagnostic criteria may remain without any specific diagnosis for months. Laboratory markers can assist in the diagnosis and management of these diseases. Previous studies suggest serum kynurenine-tryptophan pathway products and serum neopterin as biomarkers for CNS autoimmune diseases. Because urine is a reliable and repeatable source for analysis of these products with the additional advantage of easy sampling, we measured neopterin concentrations in serum and urine samples, urinary biopterin and serum kynurenine-tryptophan levels in autoimmune demyelinating diseases of CNS: pediatric multiple sclerosis (pMS, n = 27), MOGAD (n = 10), NMOSD (n = 5) patients and a control group consisting of healthy children or children with non-inflammatory diseases (n = 13), total 55 children. Methods were high performance liquid chromatography (HPLC) for neopterin, biopterin and creatinine in urine and kynurenine and tryptophan in serum; ELISA was used for serum neopterin. Comparison for biomarkers between all diagnostic groups showed urinary neopterin values were significantly higher in the pMS group (p = 0.002). The cut-off point determined by ROC analysis indicated urinary neopterin >167.75 µmol/mol creatinine could distinguish the patients from the controls with a sensitivity of 71% and specificity of 90%. The most significant difference was between the pMS and control groups (p = 0.002) while no difference was observed between pMS patients who were in relapse or stable state. Therefore, urinary neopterin appeared as a potential marker that could differentiate pMS from other demyelinating patient groups MOGAD and NMOSD as well as from controls. The fact that pteridine pathway products had not been studied in urine and serum in children with demyelinating disease before highlights the novelty of this study. If further research in larger samples confirm the present results, these molecules might assist the differential diagnosis of pMS from other demyelinating CNS diseases.

Neopterin, procalcitonin, total sialic acid, paraoxonase-1 and selected haematological indices in calves with aspiration pneumonia

This study aims to determine serum neopterin, procalcitonin, total sialic acid (TSA), paraoxonase-1 (PON1), and some haematological indices in calves with aspiration pneumonia (ASP). The patient group consisted of 30 calves of the Simmental breed, 0–28 days old, diagnosed with ASP upon clinical examination, anamnesis, auscultation examination, and radiographic results. The control group consisted of 10 healthy calves, otherwise with the same characteristics. A significant difference was found between calves with ASP and the control group of calves in serum iron (Fe, P &lt; 0.001), total iron-binding capacity (TIBC, P &lt; 0.05), PON1, TSA, procalcitonin, neopterin, and total leukocyte count (WBC) indices as a result of the analyses (P &lt; 0.001). Serum procalcitonin concentration was found to be 285.71 ng/ml in the ASP group and 30.34 ng/ml in the control group. Serum neopterin concentration was found to be 37.68 nmol/l in the ASP group and 15.14 nmol/l in the control group. Serum procalcitonin, neopterin, and TSA concentrations were found to be significantly higher in the ASP group compared to the control group. It was concluded that biomarkers such as serum procalcitonin, neopterin, and TSA are high in calves with ASP, and as a result, these markers provide diagnostically and prognostically important information.

Biomarkers of inflammation and left ventricular remodelling in psoriasis patients treated with infliximab.

Objective: Psoriasis is an immune mediated disorder associated with T cell activation and cardiovascular disease (CVD). We explored the association of inflammation with left ventricular (LV) remodelling in psoriasis patients receiving treatment with the tumour necrosis factor-α (TNF-α) blocker infliximab. Methods: Psoriasis patients (n = 47, age 47 ± 14 years, 66% men) and 99 control subjects without psoriasis (age 47 ± 11 years, 72% men) were examined by echocardiography in a cross-sectional study. LV remodelling was assessed by LV mass index for height in the allometric power of 2.7. Serum concentrations of C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine:tryptophan ratio (KTR) and the pyridoxic acid ratio (PAr) index were measured. Results: Serum concentration of neopterin (p = .007) was higher in psoriasis patients, while the other inflammatory biomarkers had similar levels. LV mass index was lower in patients than controls (35.6 ± 9.6 g/m2.7 vs. 40.3 ± 9.8 g/m2.7, p = .008). In the total study population, serum SAA (β = 0.18, p = .02), KTR (β = 0.20, p = .02) and the PAr index (β = 0.26, p = .002) were all associated with higher LV mass index independent of age, sex, body mass index, hypertension, smoking, renal function and psoriasis. Also in psoriasis patients, higher SAA level (β = 0.34, p = .02), KTR (β = 0.32, p = .02) and the PAr index (β = 0.29, p = .05) were associated with higher LV mass index independent of body mass index, hypertension and diabetes. Conclusion: Higher levels of the inflammatory biomarkers SAA, KTR and the PAr index were associated with greater LV mass index in psoriasis patients, indicating a role of chronic inflammation in LV remodelling evident even during treatment with TNF-α blockers.

Circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during chemoradiation in patients with cervical carcinoma

Abstract The aim of this study was to investigate the changes in circulating concentrations of citrulline, neopterin, kynurenine, and tryptophan during the course of chemoradiation in patients with cervical cancer. Sixteen patients with histologically confirmed carcinoma of the uterine cervix, aged 53 ± 15 years (range 29–76 years), were included in this study. Plasma neopterin, kynurenine, and tryptophan were determined with an enzyme-linked immunosorbent assay. Plasma citrulline was measured with high-performance liquid chromatography. Compared to baseline, citrulline concentration was markedly and statistically significantly decreased at visits 2, 3, and 4, while returning to pretreatment concentrations at visit 5. A significant increase in serum neopterin concentrations was observed at visits 4 and 5. With the exception of decreased kynurenine/tryptophan ratio at visit 3, no significant changes were observed in the concentrations of kynurenine, tryptophan, and kynurenine/tryptophan ratio throughout the course of the treatment. In conclusion, present data demonstrate that citrulline concentrations decrease early and neopterin concentrations increase late during the course of chemoradiation in patients with cervical carcinoma. Citrulline represents a biomarker of intestinal toxicity in this population.

Nanomicellar Curcumin Supplementation Improves the Clinical Manifestations of HAM/TSP Patients.

HTLV-1 infection causes a chronic, progressive, demyelinating, neuroinflammatory disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Treatment of HAM/TSP patients which have high levels of proviral load and pro-inflammatory markers is a challenge for clinicians. Therefore, we aimed to investigate the immunomodulatory, anti-inflammatory, and antiviral effects of curcumin in HAM/TSP patients. In this study, 20 newly diagnosed HAM/TSP patients (2 men and 18 women) were enrolled and evaluated for clinical symptoms, HTLV-1 proviral load, Tax and HBZ expression, neopterin serum concentration, and complete blood count (CBC) before and 12weeks after treatment with nanomicellar curcumin (80mg/day, orally). Clinical symptoms such as the mean Osame Motor Disability Score and Ashworth Spasticity Scale Score were significantly improved after the treatment (P=0.001 and P=0.001). Sensory symptoms such as pain and paresthesia were significantly decreased in all of the patients (P=0.001). Furthermore, urinary disorders, including urinary frequency, incontinence, and the feeling of incomplete bladder emptying, were significantly improved (P=0.001, P=0.003, and P=0.03). However, the mean HTLV-1 proviral load (P=0.97) and CBC were similar, whereas Tax, HBZ, and neopterin levels tend to increase after the treatment (P=0.004, P=0.08, and P=0.04). Results suggest that curcumin can safely improve the clinical symptoms of HAM/TSP patients but has no observable positive effects on the HTLV-1 proviral load, Tax, and HBZ expression. Therefore, prolonged use or the use of curcumin with antiviral agents in addition to clinical signs and symptoms can reduce the HTLV-1 proviral load and the expression of functional viral factors such as Tax and HBZ.

Diagnostic and prognostic value of neopterin and RNA-ase in patients with STEMI and NSTEMI

Abstract Background Neopterin and RNA-ase are markers of inflammation with low disclosed role in diagnosis and prognosis of either STEMI or NSTEMI, although inflammation is well documented as a leader pathogenic mechanism in these pathologies. Aim Evaluation of serum admission levels of neopterin and ARN-ase in pts with STEMI and NSTEMI and their prediction value concerning the risk of MACE in 1 year of follow up period. Material and methods The admission serum concentration of neopterin and ARN-ase was determined by ELISA in 94 pts with STEMI and 92 pts with NSTEMI which was compared with normal markers appreciated in 32 healthy persons. Likewise, the rate of MACE in both groups was estimated during 1 year of post-infarction period. Diagnostic worth and MACE prediction power of markers have been established using respectively ROC curve and odds ratio. Results In patients with STEMI the serum level of neopterin was significantly increased compared with normal index by 3,5 times (11,6±3,4 vs 3,3±1,4 nM/L), but RNA-ase was significantly decreased by 43,4% (24,1±3,2 vs 42,6±5,2 nM/ml). In pts with NSTEMI neopterin level was lesser than STEMI, but significantly elevated by 39% (4,6±2,5 vs 3,3±1,4 nM/L) vs normal marker. RNA-ase level didn't significantly differ from normal level. However, adjusted to diabetes mellitus established in 19 pts, RNA-ase significantly diminished (36,4±3,9 vs 42,6±5,2 nM/ml), and its diagnostic value of NSTEMI according to ROC was 69,6% (RNA-ase level indicates inversely inflammation response, such as it breaks down extracellular RNA which has proinflammatory ability). Both markers in pts with NSTEMI and diabetes mellitus demonstrated a diagnostic value of 77,6%. In pts with STEMI highest tertile level of neopterin and lowest tertile level of ARN-ase had 2,8fold (adds ratio=2,8; CI=1,98–4,62; p&amp;lt;0,05) and 2,3fold (adds ratio=2,3; CI=1,71–3,89; p&amp;lt;0,05) higher risk of MACE development. In pts with NSTEMI the combination of these markers (highest and lowest quartile levels) also had a significant prediction regarding MACE risk (adds ratio=2,1; CI=1,86–3,77; p=0,029). Conclusions 1. In STEMI both neopterin and RNA-ase could be as diagnostic markers, due to their significant change. In NSTEMI neopterin significantly elevated, but RNA-ase didn't shift from normal. In diabetic pts with NSTEMI, however, their combination demonstrated in ROC estimation a diagnostic value of 77,6%. 2. Prediction value of markers combination regarding MACE risk in pts with NSTEMI is significant and close to each marker in partly prediction of MACE for pts with STEMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Research Institute of Cardiology, Moldova Republic of

Neopterin and biopterin levels and tryptophan degradation in patients with diabetes

This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.

Comparison of early pregnancy serum concentration of neopterin, neopterin/creatinine ratio, C-reactive protein, and chitotriosidase, in pregnant women with birth at term and spontaneous preterm birth.

Inflammatory mechanisms are involved in achieving a normal pregnancy and in the development of certain pregnancy complications. These changes are more intense in pregnant women that suffer of pregnancy complications, such as spontaneous preterm birth (SPB). This study compared the course of inflammatory markers (IM) [neopterin (Neo), neopterin/creatinine ratio (Neo/Cre), C-reactive protein (CRP), and chitotriosidase (Chito)] serum concentration in the early pregnancy of women with birth at term (BT) and preterm birth (PB). IM concentration was measured in 90 sera sampled from 45 pregnancies with BT and 30 sera from 15 pregnancies with PB. Two sera were sampled from each pregnant woman: one in the first trimester and another one in the second trimester. Early pregnancy IM concentration showed a direct correlation with gestational age: Neo (rho=0.262, P=0.004), Neo/Cre (rho=0.372, P<0.001), CRP (rho=0.187, P=0.041), and Chito (rho=0.039, P=0.66). The correlation was present in both categories of patients with BT and PB. Patients with PB before 34 week of pregnancy (wp) and 32 wp showed higher Neo and Neo/Cre concentration than BT patients. A significant association was found between the risk of PB before 34 wp, PB before 32 wp, and Neo concentration (PB <34 wp: odds ratio (OR) =5.13, P=0.035) (PB <32 wp: OR=8.2, P=0.020) and, respectively, Neo/Cre concentration (PB <34 wp: OR=5.29, P=0.015) (PB <32 wp: OR=9.25, P=0.006). No association between CRP or Chito and PB age was found. IM concentration correlates with the gestational age at the time of blood sampling. Increased Neo and Neo/Cre concentration are associated with PB. Further studies are needed to evaluate the usefulness of these markers in clinical practice.

A Phase 1 study comparing subcutaneous and intramuscular routes of administration of peginterferon beta-1a: macrophage-producing neopterin levels as biomarker

Abstract Background Developing effective therapies for patients can be difficult as many fail due to safety concerns. Changes in route of administration (ROA) for approved therapies offers options to patients while mitigating known side effects. Peginterferon beta-1a (PEG) is approved for subcutaneous (SC) administration at 125 mcg every 2 weeks for patients with relapsing forms of multiple sclerosis. Intramuscular (IM) administration is associated with a different safety profile from SC and could offer patients receiving PEG an additional treatment option. To confirm efficacy is maintained, neopterin – a reliable pharmacodynamic measure for IFN therapies that is produced by macrophages – was tested in a bioequivalence study. Methods A two-period, crossover study with healthy volunteers who received a single dose of PEG administered SC followed by a single dose administered IM (or vice versa) was conducted. Blood samples were collected up to 504 hours post dose to evaluate pharmacokinetic and pharmacodynamic measures, including neopterin. Results The study enrolled 136 participants. Serum neopterin concentrations following SC and IM administration were similar, with maximal concentrations (Epeak) reached at a median ETmax of 40.1 hours and 44.0 hours, respectively. Geometric mean neopterin levels increased from baseline to maximum concentration similarly between both routes, with an increase from 8.0 to 22.6 nmol/L for SC and from 8.1 to 23.2 nmol/L for IM. The overall exposure to neopterin was also similar between both routes. Conclusion These results demonstrate no major difference in PEG activity; therefore, PEG administered SC or IM is expected to have a comparable pharmacological impact on the body.

The role of regulatory T cells in allergic rhinitis and their correlation with IL-10, IL-17 and neopterin levels in serum and nasal lavage fluid.

Allergic rhinitis (AR), is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs) and inflammatory cytokines have been shown to play a critical role in allergic airway inflammation. The aim of the study was to compare the levels of blood T lymphocyte subsets and IL-10, IL-17 and neopterin concentrations in serum and nasal lavage of patients with AR compared to healthy subjects. The study included 38 subjects with moderate-severe AR and 36 sex- and age-matched controls. Peripheral blood CD3+, CD3+CD4+ and CD4+CD25+Foxp3 percentages were evaluated using flow cytometry. Levels of IL-10, IL-17 and neopterin were measured both in serum and nasal lavage fluid with ELISA and HPLC, respectively. No difference was found in the percentages of T lymphocyte subsets between the two groups (p > 0.05). Serum IL-10 levels were similar (p > 0.05), whereas nasal IL-10 was lower in AR subjects compared to control group (2.22 ± 0.91 and 3.12 ± 1.45pg/ml, respectively) (p < 0.05). Mean serum and nasal IL-17 were higher in AR (107.7 ± 79.61 and 527.36 ± 738.7pg/ml) than the control group (76.29 ± 28.94 and 328.9 ± 430.8pg/ml) (p < 0.05 and p > 0.05). There were no significant differences in serum and nasal neopterin levels (p > 0.05). Although there were no differences in the distribution of lymphocyte subsets between the AR and control groups, the finding of higher levels of serum and nasal IL-17 and lower levels of nasal IL-10 support the cytokine imbalance in the pathogenesis of AR.

Serum Neopterin Levels and the Clinical Presentation of COVID-19

AbstractIn Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) &gt; 2.8 compared to those with a dNLR ≤ 2.8 (p&lt; 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.