Neopterin Research Articles

Development and Validation of a Fecal Extraction Procedure for the Assessment of Multiple Fecal Biomarkers of Intestinal Inflammation (P13-025-19)

ObjectivesFecal biomarkers have emerged as an important tool to assess intestinal inflammation and permeability. Commonly measured biomarkers include calprotectin (CP), myeloperoxidase (MPO), alpha-1-antitrypsin (AAT) and neopterin (NEO). We sought to develop a simple, fast and cost-effective single extraction procedure for use in determining all four biomarkers of interest. The applicability and sensitivity of this procedure for use in healthy adults was examined. MethodsSample extraction buffers and methods including sample weight, dilution, homogenization and centrifugation were all considered in the development of a single extraction procedure. An extraction buffer that included phosphate-buffered saline, phenylmethylsulfonyl fluoride, bovine serum albumin and Tween 20 was used to extract fecal samples. To assess the applicability and sensitivity of the single extraction procedure, concentrations of CP, MPO, AAT and NEO were measured using commercially available sandwich ELISA kits, according to manufacturer’s instructions. ResultsCP, MPO and AAT concentrations were measured in fecal samples of healthy adults (aged 50–80 years, n = 85) and found to be comparable to findings of previously published studies in healthy populations. Mean concentrations of CP and AAT were 3.6 ± 3.8 μg/g of wet weight (range 0.14–18.0 μg/g) and 2.3 ± 0.73 μg/g (range 0.76–5.2 μg/g), respectively. Mean fecal MPO concentrations were 135 ± 24 ng/g (range 3–1290 ng/g). NEO concentrations were examined in a subset of healthy adults (n = 10), with mean concentrations of 18 ± 1 ng/g (range 17–20 ng/g). ConclusionsWe demonstrated the efficacy of a single extraction procedure used to assess multiple fecal biomarkers of intestinal inflammation. This simple, fast and inexpensive extraction method will facilitate the determination of multiple fecal biomarkers which is critical in validating their use as clinical or predictive biomarkers of intestinal inflammation. Funding SourcesSupported by the U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. 58–1950-4–003, the Bill & Melinda Gates Foundation and Canadian Institutes of Health Research Postdoctoral Fellowship.

Biomarkers of Environmental Enteric Dysfuction and Associations with Child Linear Growth in Rural Odisha, India (OR10-06-19)

ObjectivesIntestinal dysfunction due to mucosal inflammation, known as environmental enteric dysfunction (EED), has been hypothesized to contribute to stunting in low- and middle-income countries (LMICs). Given that consensus is lacking on gold standard biomarkers for EED and on relationships with child linear growth, we examined three biomarkers of EED and height-for-age z-score (HAZ) among children under age five years in rural Odisha, India. MethodsWe conducted a sub-study within Gram Vikas MANTRA, a matched cohort study of a household-level water and sanitation intervention in Odisha, India. We collected stool samples and anthropometry data for children under age 5 (N = 209) in two rounds (October 2016 – January 2017 and July – October 2017). We analyzed stool samples for three biomarkers of EED: myeloperoxidase (MPO), neopterin (NEO), and α1-anti-trypsin (AAT). We assessed correlations between values and used linear regression to analyze associations between each biomarker and HAZ. All analyses were adjusted for relevant covariates and village-level clustering. ResultsMean HAZ for children under 5 in our sample population was -1.52 (SD: 1.34). Median biomarker values (25th, 75th percentiles) were 1052.71 ng/ml (682.76, 3208.22) for MPO, 2104.21 nmol/L (1193.64, 3490.10) for NEO, and 0.406 mg/g (229.44, 743.78) for AAT. Correlations between the biomarkers were relatively low, with the highest correlation (ρ = 0.45) between MPO and AAT. We observed an inverse association between MPO and HAZ (β = -0.000027, P < 0.001) but no association between NEO and HAZ (β = 0.000031, P = 0.46) or AAT and HAZ (β = -0.000072, P = 0.52). ConclusionsIn our sample population, median values for NEO and AAT were similar to those from other studies of children in LMICs. MPO had substantially lower values than in other reports but was still strongly associated with HAZ. Previous studies have produced conflicting evidence on relationships between each biomarker of EED and HAZ. Our results contribute evidence that intestinal inflammation may play an important role in growth faltering in young children, possibly through mucosal dysfunction. MPO is a major component of the primary granules in neutrophils and hence reflects luminal neutrophillic infiltration. Priorities for a future research agenda on EED and growth will be discussed. Funding SourcesBill and Melinda Gates Foundation.

The role of neopterin and anti-Mullerian hormone in unexplained recurrent pregnancy loss – a case-control study

This case-control study was conducted to assess whether neopterin (NP) and anti-Mullerian hormone (AMH) can be used as markers in the condition of unexplained recurrent pregnancy loss (RPL). To the best of our knowledge, this is the first work which has studied the association between AMH, NP and RPL. A total of 110 patients were included; 53 women who had at least two consecutive unexplained miscarriages (<12 weeks) made up the study group. The control group was established from 57 women who never had a miscarriage and had at least one healthy birth history. Peripheral blood samples were collected from each patient to analyse the AMH and NP concentrations. The results suggested that mean level of AMH (1.38 ± 0.683 ng/ml) in the patient’s group was significantly lower than the control group (1.84 ± 0.718 ng/ml). The mean levels of NP were significantly higher in the patient group (1.69 ± 0.486 vs. 1.38 ± 0.431 ng/ml).IMPACT STATEMENTWhat is already known about this subject? To the best of our knowledge, no previous studies about the association among AMH, NP and RPL were found in the literature.What do the results of this study add? This pioneer study demonstrates the significant relationship between the unexplained RPL with the increased levels of NP and decreased AMH.What are the implications of these findings for clinical practice and/or further research? NP and AMH may play an effective role in illuminating the condition of unexplained RPL. High levels of NP and low values of AMH in patients with RPL can be used as predictive markers for this clinical situation. If the causes of high levels of NP and low levels of AMH can be better illuminated, new treatments towards these causes can be developed to help such patients become childbearing.

Serum Neopterin in Differential Diagnosis of Bacterial Diarrhea in Pediatric Patients

Abstract Background: Neopterin, regarded as a marker of cellular immune activation, has been used in diagnosis of infection caused by intracellular pathogens. We have aimed to evaluate the clinical usefulness of serum neopterin (NPT) in acute bacterial diarrhea caused by group C enteropathogenic Escherichia coli (EPECs) and group D Salmonella spp. Methods: Serum concentration of NPT was determined by ELISA. The study group included 47 children with diagnosis of bacterial diarrhea: 32 caused by group C enteropathogenic Escherichia coli (EPECs) and 15 by group D Salmonella spp. 105 healthy children constituted the control group. Results: Serum concentration of NPT in children infected with group D Salmonella spp. turned out to be higher than in the other groups. The fraction of Salmonella-infected patients with serum neopterin above 11 nmol/l proved higher as compared to children with diarrhea caused by group C EPECs or to the healthy controls. The prevalence of a C-reactive protein (CRP) to NPT ratio of greater than 1 did not differ significantly between children with diarrhea of various etiology. Conclusions: Neopterin can be used as a non-specific marker differentiating between bacterial diarrhea of various etiology.

Serum level assessment of serum level of Neopterin (NP) and Anti-Cyclic Citrullinated Peptide (ACCPA) Antibody as markers of disease severity in rheumatoid arthritis

Serum level assessment of serum level of Neopterin (NP) and Anti-Cyclic Citrullinated Peptide (ACCPA) Antibody as markers of disease severity in rheumatoid arthritis

Association of intestinal pathogens with faecal markers of environmental enteric dysfunction among slum-dwelling children in the first 2 years of life in Bangladesh.

ObjectiveEnvironmental Enteric Dysfunction (EED) can be assessed by faecal biomarkers such as Myeloperoxidase (MPO), Neopterin (NEO) and Alpha‐1 anti‐trypsin (AAT). We aimed to test the association of intestinal pathogens with faecal markers of EED among slum‐dwelling children in first 2 years of life.MethodsThe MAL‐ED birth cohort data of Bangladesh site were used to conduct this analysis. Multivariable analyses using Generalized Estimating Equations (GEE) were performed to test the association between intestinal pathogens and faecal markers of EED.ResultsGiardiasis, ascariasis and trichuriasis were the most frequent parasitic infections and Campylobacter spp., Enteroaggregative Escherichia coli (EAEC) and Enterotoxigenic Escherichia coli (ETEC) were the common bacterial pathogens observed in stool samples of the children. Overall, 71%, 97% and 58% of stool samples were above values considered normal in non‐tropical settings for MPO, NEO and AAT respectively. Giardiasis was found to be significantly associated with MPO (Coefficient = 0.55; 95% CI = 0.15, 0.95; P‐value = 0.008) and AAT concentrations (Coefficient = 0.34; 95% CI = 0.04, 0.63; P‐value = 0.03). A significant association was found between trichuriasis and NEO (Coefficient = 0.90; 95% CI = 0.19, 1.61; P‐value = 0.01). Trichuriasis (Coefficient = 1.71; 95% CI = 0.32, 3.11; P‐value = 0.02) and giardiasis (Coefficient = 1.51; 95% CI = 0.79, 2.23; P‐value <0.001) were significantly associated with EED score. Children with EAEC had significantly higher MPO concentrations (Coefficient = 0.33; 95% CI = 0.06, 0.61; P‐value = 0.02).ConclusionThe study results imply the importance of intestinal pathogens in contributing to intestinal inflammation and increased intestinal permeability in young children.

The early diagnostic value of serum neopterin and cartilage oligomeric matrix protein for osteoarticular changes among brucellosis patients at an early period

BackgroundBrucellosis is an important public health problem in China. Brucellosis can cause many osteoarticular changes, especially chronic brucellosis. Brucellosis presents various diagnostic difficulties because it mimics many other diseases. Because of the poor sensitivity and ability of X-ray image, it is necessary to find a good method of early diagnosis for osteoarticular changes among brucellosis patients at an early period.The aim of this study was to find early changes biomarkers for osteoarticular changes among brucellosis patients at an early period and provide a better understanding of the osteoarticular changes in this disease at an early stage.MethodsSixty-one cases of brucellosis patients at an early period (within 6 months) and 67 cases of volunteers were selected and divided into brucellosis vs. control groups. Serum samples were detected with serological tests for brucellosis, including rose bengal plate test (RBPT), agglutination test (SAT), and IgG and IgM with ELISA. Meanwhile, cartilage oligomeric matrix protein (COMP) and neopterin (NPT) levels in all samples were measured simultaneously with ELISA. The data were analyzed using SPSS 17.0 software.ResultsTogether with the clinical examination, epidemiological investigation, and serological tests of RBPT, SAT, and IgG and IgM with ELISA, the patients from brucellosis group all were diagnosed as brucellosis cases at an early period, while the results of RBPT, SAT, and IgG and IgM with ELISA from the healthy control group were negative. Comparing with the healthy control, the medians of serum NPT and COMP in the patients group were 9.26 ng/l, 1.70 ng, respectively, which were higher than that of the healthy control group with significant differences (Z = 5.512, 3.614, all p = 0.000).ConclusionThe serum NPT and COMP levels of brucellosis patients at an early period were increased. The serum NPT and COMP levels might be the indicator biomarker for osteoarticular changes of human brucellosis at an early stage.

Environmental Enteropathy, Micronutrient Adequacy, and Length Velocity in Nepalese Children: the MAL-ED Birth Cohort Study.

Environmental enteropathy (EE) is likely associated with growth retardation in children, but the association between EE and length velocity z score (LVZ) has not been investigated. The objective of the study was to assess associations between fecal markers for intestinal inflammation and LVZ and whether these associations were influenced by micronutrient adequacy among 9 to 24 months old children in Bhaktapur, Nepal. Data were divided into 5 time slots (9-12, 12-15, 15-18, 18-21, and 21-24 months). Anthropometric measurement and dietary assessment (by 24 hour recall) were performed monthly. Mean nutrient density adequacy was calculated based on nutrient density adequacy of 10 micronutrients (thiamin, riboflavin, niacin, vitamin B6, folate, vitamin C, vitamin A, calcium, iron, and zinc). Anti-1-antitrypsin (AAT), myeloperoxidase (MPO), and neopterin (NEO) were measured in stool samples collected at the beginning of each time slot. An EE score was calculated based on all 3 fecal markers. Associations between AAT, MPO, NEO and EE score and LVZ were assessed by multiple linear regression analyses and Generalized Estimating Equations models. Associations between fecal markers and EE score and LVZ were generally weak. EE score and MPO for 3-month and MPO for 6-month growth periods were significantly associated with LVZ from 9 to 24 months. These associations were slightly modified by mean nutrient density adequacy. EE score and MPO were significantly associated with LVZ in 9 to 24 months old Nepali children. Further studies to establish the usefulness of AAT, MPO, and NEO in assessing EE and growth retardation are warranted.

Antibody against low density lipoproteins (oLAb), procalcitonin and neopterin as prognostic marker during sepsis and systemic inflammatory response syndrome (SIRS)

Introduction Aim of this study was to evaluate the impact of lipid peroxidation during the course of Sepsis and SIRS in ICU patients. As a biomarker for lipid peroxidation we used antibodies against oxidized LDL (oLAb). Furthermore, we applied Procalcitonin (PCT) and C-reactive protein (CRP) as markers for inflammation as well as Neopterin (NPT) as a marker for macrophage activation. oLAb play an important role in diseases associated with lipid peroxidation, e.g. liver disease, autoimmunological diseases, adipositas, heart and circulatory failure as well as infectious diseases like sepsis or SIRS. The hypothesis concerning the prognostic value of oLAb in sepsis indicates that increasing titers seem to be wholesome in contrast to decreasing values, which seem to show overwhelming lipidperoxidation. Patients and Methods 25 patients with verified sepsis (n=13; 7 survivor, 6 non-survivor) and SIRS (n=12; 7 survivor, 5 non-survivor). Patients stayed 48 hours at the ICU under the criteria according to Roger C. BONE and Jukka TAKALA. Biomarkers were determined every day, as clinic score we used APACHE II Score during the first 24 hours. In addition, we determined Cytokines (i.e. IL-1, IL6 and IL-8). Results Surviving patients showed significant increasing oLAb titres (p Conclusion Even though the number of patients was rather small we conclude that oLAb seems to be an indicative parameter for the follow up of sepsis and SIRS besides general inflammatory markers like CRP, PCT and NPT. Beyond that, the use of antioxidant drugs like Pentoxifylin, Ascorbic acid, Selenium, Alpha-Tocopherol as well as Coenzyme Q10, Allopurinol and N-Acetyl-cystein might be useful to reduce lipid peroxidation and to improve the chance to survive. Patients receiving parenteral or enteral nutrition or via infusion of those substances would show a better outcome.

Nutrient intake and environmental enteric dysfunction among Nepalese children 9-24 months old-the MAL-ED birth cohort study.

Nutrient deficiencies limit the growth and turnover of intestinal mucosa, but studies assessing whether specific nutrients protect against or improve environmental enteric dysfunction (EED) are scarce. We aimed to investigate associations between nutrient intake and EED assessed by lactulose:mannitol (L:M) ratio, anti-1-antitrypsin, myeloperoxidase (MPO), and neopterin (NEO) among children 9-24 months in Bhaktapur, Nepal. Among 231 included children, nutrient intake was assessed monthly by 24 h recalls, and 3-month usual intake was estimated using Multiple Source Method. Associations between nutrient intake and L:M ratio (measured at 15 months) were assessed using multiple linear regression, while associations between nutrient intake and fecal markers (measured quarterly) were assessed using Generalized Estimating Equations (GEE) models. We found that associations between nutrient intake from complementary food and L:M ratio, alpha-1-antitrypsin (AAT), MPO and NEO were generally negative but weak. The only significant associations between nutrient intake (potassium, magnesium, phosphorous, folate, and vitamin C) and markers for intestinal inflammation were found for MPO. Negative but weak associations between nutrient intake and markers of intestinal inflammation were found. Significant associations between several nutrients and MPO might merit further investigation.

Neopterin as a Biomarker in Patients with Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension

Background: Upregulation of the immune system is regarded to play an important role in the etiopathobiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To the best of our knowledge, neopterin (NP) has never been investigated in patients with PAH and CTEPH. Objectives: The aim of the study was to evaluate the concentration of NP in blood in order to examine its impact on outcome and relationship with disease severity in that population. Methods: Serum concentration of NP was analysed prospectively in 50 patients (36 with PAH and 14 with CTEPH vs. 31 healthy controls) and assessed in relation to clinical parameters and outcome. Results: NP concentration in the PAH and CTEPH groups combined was significantly higher than in the control group (8.68, 6.39–15.03 vs. 5.14, 4.16–5.98 nmol/L, p < 0.0000001). During 9 months of follow-up, clinical deterioration occurred in 18 patients (including 8 deaths), and NP concentration in this group was higher when compared to stable patients (15.6, 8.52–25.13 vs. 7.87, 6.18–9.89, p = 0.002). The cutoff value of NP derived from ROC curve analysis was 15.3 nmol/L (p = 0.002, AUC 0.77, p = 0.0004, HR = 4.35, 95% CI 1.43–13.18, log-rank test). On Cox regression analysis, NP predicted clinical deterioration (p = 0.009, 95% CI 1.01–1.06). NP correlated positively with NT-proBNP (p < 0.001), red blood cell distribution width (p < 0.001), and right atrium area (p = 0.002) and inversely with 6-min walking test (p = 0.002) and peak oxygen consumption (p = 0.001). Conclusions: NP concentration is increased in patients with PAH and inoperable CTEPH. Elevated NP concentration is associated with adverse clinical outcomes and correlates with clinical parameters.

Association of Fecal Markers of Environmental Enteric Dysfunction with Zinc and Iron Status among Children at First Two Years of Life in Bangladesh.

.Environmental enteric dysfunction (EED) causes gut inflammation and increased intestinal permeability leading to deficiencies in micronutrients such as zinc and iron. Fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) can predict EED. The aim of this study was to examine the association between fecal markers of EED with zinc and iron status among children at first 2 years of life. Malnutrition and Enteric Disease Study Bangladeshi birth cohort data were used to conduct this analysis. Multivariable analyses using generalized estimating equations were performed to test the association between individual fecal markers with zinc or iron status of the children. A total of 265 children were enrolled in the study (male:female = 1:1). Of the 627 stool samples collected (N = 222 children), 535, 511, and 577 were accompanied by zinc, ferritin, and soluble transferrin receptor values, respectively. Median (interquartile range [IQR]) values of AAT, MPO, and NEO were 0.33 (0.18–0.62) mg/g, 3,895.42 (1,563.76–8,432.82) ng/mL, and 890.81 (331.57–2,089.04) nmol/L, respectively. Overall, 60%, 71%, and 97% of samples were above the values considered normal in nontropical settings for AAT, MPO, and NEO, respectively. High AAT levels were significantly associated with low ferritin values after adjusting for age and gender (coefficient = −5.85; 95% confidence interval = −11.23 to −0.47; P value = 0.03). No such association was found between AAT and plasma zinc status. Myeloperoxidase and NEO were not associated with plasma zinc or iron status. The study results imply the importance of enteric protein loss in contributing to reduced ferritin levels at first 2 years of life.

NEOPTERIN DAN PEROKSIDA SERUM SEBAGAI PETANDA MAKROFAG TERAKTIVASI PADA TUBERKULOSIS PARU AKTIF DAN INDIVIDU BERKEBAHAYAAN TINGGI (Serum Neopterin and Peroxide As Marker of Activated Macrophages on Active Pulmonary Tuberculosis and Individuals At High Risk)

Failure of macrophages to phagocytize Mycobacterium tuberculosis causes the release of hydrogen peroxide/peroxide (H2O2) bythe activated macrophages. Neopterin is one of the most important markers in the activated macrophages. Neopterin is a pteridinederivative produced by the activated macrophages through the stimulation of interferon gamma. Increased levels of Neopterin has beenreported in lung tuberculosis. Activation of macrophages is essential to the development of tuberculosis infection that can lead to activepulmonary tuberculosis or latent tuberculosis, in this case is a high-risk for healthy individuals. To determine the differences in serumlevels of Neopterin and H2O2 between patients with active pulmonary tuberculosis and healthy individuals at high risk of pulmonarytuberculosis. A total of 15 patients with active pulmonary tuberculosis and 15 healthy individuals at high risk examination serumNeopterin levels and peroxide (H2O2). Active pulmonary tuberculosis patients when the results of sputum smear examination chest x-raysis obtained positive results. Healthy individuals at high risk when the results of smear examination and chest x-rays is negative. Thelevel of Neopterin was examined using a double antibody sandwich immunoassay with Human neopterin (NEOP) ELISA Kit ® BioassayTechnology Laboratory. The level of peroxide was examined using quantitative colorimetric peroxidedetermination with QuantiChromTMPeroxide Assay Kit (DIOX-250)®. Neopterin serum levels between patients with active pulmonary tuberculosis and healthy individualsat high-risk were analysed by independent samples t-test. H2O2 serum levels between patients with active pulmonary tuberculosis andhealthy individuals at high-risk were analysed with Mann Whitney Test. The confidence level is p &lt;0.05. The mean Neopterin levelsin patients with active pulmonary tuberculosis was 5.17±4.64 nmol/L, the mean Neopterin levels in group of healthy individuals athigh risk was 3.97±1.79 nmol/L. Statistical analysis by the independent samples t-test found no significant differences between groupsin Neopterin serum levels of patients with active pulmonary tuberculosis and healthy individuals at high risk (p=0.357). The meanserum levels of H2O2 of group of patients with active pulmonary tuberculosis was 26.38±3.00 μM, the mean levels of H2O2of group ofhealthy individuals at high risk of 20.69±4.46 μM. Statistical analysis with non-parametric Mann-Whitney Test was found significantdifference in the peroxide (H2O2) levels between groups of patients with active pulmonary tuberculosis and group of healthy individualat high-risk (p=0.000). The levels of Neopterin in patients with active pulmonary tuberculosis was not significantly higher comparedto the healthy individuals of high risk. Levels of peroxide (H2O2) serum in patients with active pulmonary tuberculosis was significantlyhigher compared to the group of healthy individuals at high risk. This shows that there is increased activity of macrophages in patientswith active pulmonary tuberculosis, but not effective in eliminating of Mycobacterium tuberculosis.

Neopteryna jako wskaźnik stanu zapalnego i rozrostu nowotworowego w ostrych białaczkach

Introduction. Neopterin (NPT) is a sensitive marker for cellular immune responses. It is a pteridine group compound as a dye substance in insects, lower vertebrata and mammals. Neopterin is released from human monocytes, macrophages and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes. High neopterin concentrations in serum and urine were shown to be a reliable indicator for the severity of bacterial, viral infections including autoimmune diseases, allograft rejections and various malignant disorders. Aim. The aim of the study was the concentration of the neopterin in acute leukemias may be an endogenous marker of unfavorable processes in acute leukemia for which the growth of the tumor, the coexistence of inflammation. Material and methods. The studies involved 80 patients suffering from acute leukemias including 53 patients with acute myeloid leukemia, 21 patients with acute lymphoblastic leukemia and 6 patients with mixed phenotype acute leukemia. The patients with acute leukemia was analyzed as a group with inflammatory condition and a group without inflammatory condition. The quantitative assessment of serum neopterin level was performed by means of immunoenzymatic test ELISA. Results. Patients with all types of leukemia showed elevated serum neopterin levels in comparison to the control group and significantly elevated neopterin levels in patients with coexisting inflammation compared to the values of these parameters in patients without inflammation. The neopterin concentration was highest in the group of patients diagnosed with acute M4 and M5 leukemia, both without inflammation (32.8 ± 13.6 nmol/l) and with co-existing inflammation (116.57 ± 97.0 nmol/l) (p = 0.00024). Conclusions. Neopterin as a marker of malignant hyperplasia may be used only in cases where inflammation does not occur.

Immunological Evaluation of Psoriatic Patients In Erbil City/Iraq

Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The immunopathogenesis of this disease is complex and involve alternations in the innate and acquired immune system through cytokines that released by keratinocytes and inflammatory leukocytes contribute to the induction and persistence of inflammatory processes in psoriasis. This study was carried out to evaluate the immunological aspects in psoriasis patients attended consultation clinics of dermatology at Hawler Teaching Hospital in Erbil city/Iraq. Blood samples were obtained from 50 psoriatic patients and 30 healthy controls. Serum neopterin (NPT), tumor necrosis factor-alpha (TNF–α), interleukin-10 (IL–10), interleukin-22 (IL–22), high sensitive C-reactive protein (hsCRP), and malondialdehyde (MDA) levels were estimated in the patients. The result showed that serum TNF-α, IL-22, NPT, hsCRP, and MDA were highly significant in the psoriatic patients compared to healthy controls (p< 0.05), while serum IL-10 showed no significant difference between psoriatic patients and healthy controls. The study revealed that elevation of serum NPT, TNF-α, IL-22, hsCRP, MDA in one hand, and impaired IL-10 expression, on the other hand, are involved in the pathogenesis of psoriasis by induction and maintenance of psoriatic lesion. The dysregulation of IL-10 is associated with enhanced immunopathology and increased risk for chronic non-healing infection in psoriasis patients. Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The immunopathogenesis of this disease is complex and involve alternations in the innate and acquired immune system through cytokines that released by keratinocytes and inflammatory leukocytes contribute to the induction and persistence of inflammatory processes in psoriasis. This study was carried out to evaluate the immunological aspects in psoriasis patients attended consultation clinics of dermatology at Hawler Teaching Hospital in Erbil city/Iraq. Blood samples were obtained from 50 psoriatic patients and 30 healthy controls. Serum neopterin (NPT), tumor necrosis factor-alpha (TNF–α), interleukin-10 (IL–10), interleukin-22 (IL–22), high sensitive C-reactive protein (hsCRP), and malondialdehyde (MDA) levels were estimated in the patients. The result showed that serum TNF-α, IL-22, NPT, hsCRP, and MDA were highly significant in the psoriatic patients compared to healthy controls (p< 0.05), while serum IL-10 showed no significant difference between psoriatic patients and healthy controls. The study revealed that elevation of serum NPT, TNF-α, IL-22, hsCRP, MDA in one hand, and impaired IL-10 expression, on the other hand, are involved in the pathogenesis of psoriasis by induction and maintenance of psoriatic lesion. The dysregulation of IL-10 is associated with enhanced immunopathology and increased risk for chronic non-healing infection in psoriasis patients.

Role of Alvarado score and biological indicators of C-reactive protein, procalicitonin and neopterin in diagnosis of acute appendicitis.

The determination of a definitive preoperative diagnosis of acute appendicitis (AA) remains a challenge; however, delays in diagnosis increase complication rates. The aim of this study was to investigate the contribution of the Alvarado score (AS) alone and the AS combined with the use of the biological indicators of C-reactive protein (CRP), procalcitonin (PCT) and neopterin (NP) in the diagnosis. Serum was collected from 100 patients who were admitted to the general surgery clinic of Istanbul University, Cerrahpasa Medical Faculty between March 4, 2014 and July 29, 2015 with the pre-diagnosis of AA and who agreed to take part in the study. The serum samples were stored at -70°C. The patients were divided into 2 groups: AA-positive (n=60) and AA-negative (n=40). The AA positive group was divided into subgroups of complicated (n=11), uncomplicated AA (n=49) and the AS, CRP, PCT, NP levels were compared. The study population consisted of 45 men (45%) and 55 women (55%), with a mean age of 32.8+-13.7 years (range: 18-92 years). There was no significant difference between the groups in age and gender. There were 24 patients with an AS ≤4 (3 had surgery), 35 patients with an AS of 5-7 (22 had surgery), and 41 patients with an AS of 8-10 (38 had surgery). Three of the 63 patients who underwent surgery were diagnosed with a normal appendix. The serum CRP, PCT, and NP measures were found to be inadequate to make an AA diagnosis alone, these values increased the sensitivity and specificity of the AS. The biological indicators were also significant in differentiating between the complicated and uncomplicated AA groups (p<0.05). Although the AS is useful, additional testing and clinical approaches are valuable to inform the diagnostic procedure. When considered alone, serum CRP, PCT and NP values are insufficient for a diagnosis of AA. However, they increased the diagnostic value of the AS and can be helpful in distinguishing complicated AA cases.

The predictive effect of inflammatory markers and lipid accumulation product index on clinical symptoms associated with polycystic ovary syndrome in nonobese adolescents and younger aged women

Objective(s)The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. Study designA total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMI<25). Neopterin (NEO), C-reactive protein (CRP) levels and complete blood parameters were assessed. LAP index and homeostasis model assessment of IR (HOMA-IR) were calculated; anthropometric, clinical and biochemical parameters were also recorded. ResultsSerum NEO, CRP levels and LAP index were significantly increased in nonobese adolescents and younger aged females with PCOS compared to healthy controls. We could not found any predictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Conclusion(s)Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS.

Diagnostic and Prognostic Value of Inflammatory Parameters Including Neopterin in the Setting of Pneumonia, COPD, and Acute Exacerbations

ABSTRACTAcute exacerbations and community-acquired pneumonia (CAP) are severe complications in patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed inflammatory parameters in serum including C-reactive protein (CRP), procalcitonin (PCT), and serum neopterin (NPT) to determine their potential to differentiate between patients with CAP+COPD and with acute exacerbations of COPD (AECOPD) without pneumonia. 102 (39 women and 63 men) patients were included in this retrospective study, of whom 48 presented with CAP without underlying COPD, 20 with CAP+COPD and 34 with AECOPD. CRP, PCT, and blood counts were determined by routine automated tests, and NPT concentrations were determined by ELISA. The ratios of CRP to NPT levels were calculated. Upon patient admission, CRP, PCT, and NPT levels were significantly higher in patients with CAP compared to those in AECOPD patients. CRP/NPT ratio was lower in AECOPD compared to CAP (+/−COPD) patients. Positive correlations were found between duration of hospitalization and CRP levels and the CRP/NPT ratio at study entry. Patients who were readmitted within 30 days tended to have higher NPT levels at initial presentation. Patients under ongoing corticosteroid treatment presented with lower inflammatory parameters. The CRP/NPT-ratio was suited well to discriminate between AECOPD and CAP on the basis of COPD, a CRP/NPT cutoff of 0.346 provided a sensitivity of 65% and a specificity of 79%. The combinatory use of inflammatory patterns might help to differentiate patients with AECOPD from those with CAP on the basis of COPD.

The value of neopterin used in diagnosis and risk stratification of sepsis

Objective To explore the value of neopterin (Np) in early diagnosis and risk stratification of sepsis. Methods A total of 82 patients admitted to the emergency department from April 2013 to February 2014 were enrolled in the study. They were divided into two groups: sepsis-free group (n= 8) and sepsis group (n=74). Patients' APACHE II scores were calculated within 24 hours after admission, and then their plasma levels of Np and procalcitonin (PCT) were detected and analysis was carried out to find the correlation between plasma levels of Np, PCT and acute physiology and chronic health evaluation Ⅱ score (APACHE Ⅱ score) in two groups. And 74 patients in sepsis group were further divided into three subgroups according to their APACHE Ⅱ score : Ⅰ subgroup (score ﹤ 15 , n= 27), Ⅱ subgroup (score 15 to 24 , n=32), and Ⅲ subgroup (score > 25 or more, n= 15). The differences in plasma Np and PCT levels were compared among three subgroups and correlation analysis of Np levels with PCT levels and APACHE Ⅱ scores was carried out. Results The plasma levels of Np, PCT and APACHE Ⅱ scores in sepsis group were higher than those in sepsis-free group (P<0.05). In sepsis group, the plasma levels of Np and PCT were gradually increased with the increasing severity of sepsis (P<0.05); In sepsis group, the plasma levels of Np, PCT and APACHE Ⅱ scores were positively correlated (P<0.01). The area under receiver operating characteristic curve (ROC) of Np was 0.79 and the area under ROC of PCT was 0.75, both of which had high diagnostic accuracy. Conclusions Neopterin has greatly useful value in early diagnosis and risk stratification of sepsis. Key words: Neopterin; Procalcitonin; Sepsis; APACHE Ⅱ score; Receiver operating characteristic curve; Application value

Serum Neopterin: A Potential Marker for Screening Blood Donors.

To determine serum neopterin levels in blood donors of local population and its association with transfusion transmitted infections. A cross-sectional observational study. Department of Physiology, Liaquat National Hospital and Medical College (LNHMC) in collaboration with Basic Medical Sciences Institute (BMSI) and Jinnah Postgraduate Medical Centre (JPMC), Blood Bank, Karachi, Pakistan, from January to June 2015. During this period, a total of 174 blood donors were selected through random sampling technique. All participants fulfilling the inclusion criteria involving apparently healthy blood donors of either gender within the age bracket of 18 - 60 years and consenting to participate were selected. The participants were screened for transfusion transmitted infections as per WHO recommendations through the standard procedures used for screening at the JPMC blood bank. The demographic profile, anthropometric measurements and vitals were recorded for every participant. Serum neopterin was measured using ELISA kits. Data was analysed on SPSS version 21. ANOVA and chi-square tests were applied as tests of significance at a p-value of <0.05. The neopterin content in the sera of disease negative blood donors was 6.23 ±2.19 nmol/l as compared to disease positive blood donors, in whom the neopterin level was increased to 15.10 ±4.93 nmol/l (p =0.001). The neopterin assay has the potential to detect a number of transfusion transmissible viral diseases; which may, or may not be revealed by the usually employed battery of routine tests. We conclude that the risk of transfusion transmitted pathogens in our population can be reduced significantly, using neopterin assay as a routine in blood banks.