Neopterin Research Articles

Clinical study on the relationship between neopterin and polycystic ovary syndrome

Objectives: Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disorder. To offer new research direction for PCOS, including its pathogenesis and treatment, this research explores the relationship between neopterin (NPT) and polycystic ovary syndrome. Material and Methods: This is a prospective study. 80 cases with PCOS were selected in the reproductive medicine clinics of the Second Affiliated Hospital of Shandong First Medical University as PCOS group from January 2020 to December 2021. 80 cases with normal pregnancy plan were treated as non-PCOS group, whose menstruation is from 25 days to 35 days. We divided the two groups into two subgroups separately according to their body mass index (BMI): the obese one with BMI≥25kg/m2 and non-obese one with BMI<25kg/m2. Results: The expression levels of triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), C-reactive protein (CRP), neutrophil (N), NPT and interleukin-6 (IL-6) in PCOS group were higher than non-PCOS group. CRP, NPT and IL-6 in the obese group were increased than the non-obese group in the pairwise comparison of its subgroups whether in PCOS group or non-PCOS group. In the analysis of linear correlation, NPT was positively correlated with TG, TC, WBC, N, CRP, FINS, IL-6 and TNF-α (P<0.01). Multivariate Stepwise regression analysis found that FINS and IL-6 was the two most important factors. Conclusion: The expression of NPT in PCOS patients was higher than non-PCOS. NPT maybe play a significant role in the development of PCOS.

Tryptophan-kynurenine metabolism during acute alcohol withdrawal in patients with alcohol use disorder: The role of immune activation.

Recent research has suggested that excessive alcohol consumption in patients with alcohol use disorder (AUD) is associated with chronic immune activation, which affects the metabolism of the neurotransmitter precursor amino acid tryptophan (TRP) and contributes to the complex pathophysiology of AUD. Our study investigated possible immune-associated alterations of TRP to kynurenine (KYN) metabolism in patients with AUD during acute alcohol withdrawal. We measured serum concentrations of TRP, KYN, quinolinic (QUIN), kynurenic acid (KYNA), and the immune activation marker neopterin (NEO) at the first, fifth and 10th day of alcohol withdrawal in patients with AUD, who attended a standardized in-patient treatment program and underwent a detailed clinical assessment. Data from these individuals were compared to data from a reference control group (RCG). The primary outcome measures were the differences in serum concentrations of metabolites between AUD patients and RCG and correlations between NEO and metabolites of the tryptophan-kynurenine pathway. r=0.695, p < 0.001) in the AUD group. Mixed models analysis showed that NEO concentrations were positively associated with QUIN but not with KYNA concentrations. Several behavioral symptoms correlated positively with QUIN concentrations and negatively with the KYNA/QUIN ratio. Our findings demonstrate that the changes in TRP catabolism in acute alcohol withdrawal resulting in increased KYN production could reflect the involvement of immune-associated activation of the enzyme indoleamine 2,3-dioxygenase, as NEO concentrations correlated with the KYN/TRP ratio. In addition, our data show that this low-grade immune activation may cause an imbalance in the production of neurotoxic and neuroprotective kynurenine metabolites in AUD.

Association between intestinal bacterial carriage, biomarkers of environmental enteric dysfunction, and stunting in rural Malawian children

Background. Available data from murine studies suggest that intestinal bacteria may have a role in modulating growth phenotypes in the host. We investigated the prevalence of four gut bacteria known in murine models to impair growth (Bifidobacterium longum, Faecalibacterium prausnitzii, Dorea formicigenerans, and Akkermansia muciniphila), the level of fecal biomarkers of environmental enteric dysfunction (EED) and stunting in rural Malawian children. Methods. DNA and protein were extracted from fecal samples of rural Malawian children (aged 1-59 months) at a baseline cross-sectional survey in the Mangochi district of Malawi conducted within the framework of the Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial. Intestinal carriage of bacteria was measured by PCR. Neopterin (NEO), myeloperoxidase (MPO), and alpha-1 antitrypsin (AAT), biomarkers of EED, were measured by an enzyme-linked immunosorbent assay (ELISA) test. Height-for-age Z (HAZ) score &lt;-2 defined stunting. Tests of proportions and regression models were used to explore the relationship between bacterial carriage, EED, and stunting. Results. Fecal samples from 613 children were available for laboratory analyses. F. prausnitzii and D. formicigenerans were prevalent in over 70% of children while B. longum was the least prevalent. B. longum carriage in younger children was associated with elevated EED biomarkers. Two thirds of children had elevated NEO, 33% had elevated MPO, and 16% had elevated AAT. Stunting was found in 38%. No significant associations were found between EED biomarkers or intestinal bacteria carriage and stunting. Conclusion. Intestinal carriage of these four bacteria was not associated with stunting in Malawian children. Carriage was also not associated with EED, nor EED biomarker levels associated with stunting. Further factors acting in concert are necessary to impact EED, perturb growth, and alter gut bacterial carriage.

Inflammatory and autoimmune predictive markers of response to anti-PD-1/PD-L1 therapy in NSCLC and melanoma.

Immune checkpoint inhibitors (ICI) are a standard in cancer therapy, but few patients respond to the treatment. The aim of the present study was the determination of immunological markers for monitoring response to ICI. The present study included 74 patients receiving ICI in subsequent [group 1; non-small cell lung cancer (NSCLC)] and first-line setting (group 2; melanoma) and 30 patients with NSCLC receiving first-line chemotherapy. In groups 1 and 2 β-2 microglobulin (B2-MG), neopterin (NPT), IL-6, IL-18, HLA-DRB1 and autoantibodies were assessed after two months of ICI, and before the start of next administration in group 3. In group 1 low level of B2-MG (P<0.0001), NPT (P<0.0001), IL-6 (P<0.0001), IL-18 (P=0.0003), HLA-DRB1*03 (P=0.016) and anti-TPO antibodies (P=0.016) were associated with response >six months. In group 2 high level of B2-MG (P=0.0001), NPT (P=0.0016), IL-6 (P=0.013) and IL-18 (P=0.032) were associated with early disease progression (<six months). Univariate analysis demonstrated that immune-related adverse events were predictive marker of prolonged progression-free survival (PFS) in group 1 (P=0.038) and 2 (P=0.020). Neutrophil-lymphocyte ratio ≥5 before immunotherapy was correlated with shorter PFS in melanoma in multivariate analysis (P=0.007). B2-MG ≥2.5 mg/ml (P=0.006) and NPT ≥12 nmol/l (P=0.027) were predictors of shorter PFS in group 1. B2-MG ≥2.5 mg/ml was predictor of shorter PFS (P=0.008) in group 2. In group 1 levels of B2-MG, NPT, IL-6 and IL-18 were higher than in group 3. In summary, immunological markers are promising predictive markers for immunotherapy; however, it requires further prospective studies.

Diagnostic power of laboratory methods for assessing ulcerative colitis severity: A prospective comparative study

Background. The epidemiology of ulcerative colitis in the Russian Federation is typified by late diagnosis and the predominance of severe complications entailing high mortality.Objectives. A comparison of the diagnostic value of laboratory methods for assessing ulcerative colitis severity.Methods. A total of 178 ulcerative colitis patients were divided into 4 cohorts by the presence and severity of attack; a control cohort included 40 healthy volunteers. Besides standard tests, a cytokine profile was determined in all patients: IL-1 IL-2, IL-4, IL-6, IL-10, TNF-α, IL-17; faecal inflammation marker concentrations — lactoferrin (LF), calprotectin (CalP), neopterin (NP); optical anisotropy (OA) of neutrophilic granulocyte nuclei; clinical activity index (CAI); Mayo scores. A single-factor analysis of variance was performed to compare the diagnostic value of laboratory tests, with a Mayo score taken as the factor reflecting ulcerative colitis attack severity. Differences were assumed statistically significant at p &lt; 0.05. Results. The patients suffering from ulcerative colitis exhibited statistically significant Mayo score correlations with IL-6 (r = 0.598, p = 0.001), IL-17 (r = 0.587, p = 0.005), TNF-α (r = 0.701, p = 0.001), CalP (r = 0.881, p = 0.001), LF (r = 0.799, p = 0.001), NP (r = 0.791, p = 0.001) and OA (r = –0.877, p = 0.001). Faecal inflammatory biomarkers varied in the range from 73.4 (NP) to 95.3% (CalP) of total variance. Serum markers varied from 75.2 (IL-6) to 88.1% (IL-17) of total variance. As of all markers, the highest diagnostic value was observed for CalP (95.3% of total variance), while the lowest — for NP (73.4% of total variance). In the analysis of variance, the cut-off values for serum markers in predicting endoscopically active disease (&gt;1 Mayo score) comprised: IL-6 = 10.3 pg/mL; IL-17 = 18.5 pg/mL; TNF-α = 10.9 pg/mL. The analogous values for faecal markers were: CalP = 112.0 μg/g; LF = 80.9 μg/g; NP = 92.8 μg/g. Neutrophilic granulocytes optical anisotropy comprised 94.5% of total variance, which compares with CalP by diagnostic power.Conclusion. A high diagnostic power has been demonstrated for faecal inflammatory markers (calprotectin, neopterin, lactoferrin), cytokines (IL-6, IL-17, TNF-α) and neutrophilic granulocytes optical anisotropy in detecting the attack relapse and severity.

Mycotoxins were not associated with environmental enteropathy in a cohort of Tanzanian children.

Enteropathy is a pathophysiological condition characterized by decreased intestinal barrier function and absorption. Past studies have hypothesized that mycotoxins might impair children's growth by causing intestinal enteropathy, including interactions between mycotoxins and pathogens. We investigated the association of two mycotoxins, aflatoxin B1 (AFB1 ) and fumonisin B1 (FB1 ), independently and in conjunction with microbial pathogens, with fecal biomarkers of environmental enteropathy in children. As part of a larger MAL-ED study, 196 children were recruited in Haydom, Tanzania, and followed for the first 36 months of life. The gut inflammation biomarkers myeloperoxidase (MPO), neopterin (NEO), and alpha-1-antitrypsin (A1AT) were analyzed in stool samples at 24 months; with mean concentrations 5332.5ng/L MPO, 807.2nmol/L NEO, and 0.18mg/g A1AT. Forty-eight children were measured for AFB1 -lys, with a mean of 5.30 (95% CI: 3.93-6.66) pg/mg albumin; and 87 were measured for FB1 , with a mean of 1.25 (95% CI: 0.72-1.76) ng/ml urine. Although the pathogens adenovirus and Campylobacter were associated with A1AT (p=0.049) and NEO (p=0.004), respectively, no association was observed between aflatoxin (MPO, p=0.30; NEO, p=0.08; A1AT, p=0.24) or fumonisin (MPO, p=0.38; NEO, p=0.65; A1AT, p=0.20) exposure and any gut inflammation biomarkers; nor were interactive effects found between mycotoxins and pathogens in contributing to intestinal enteropathy in this cohort. Although further studies are needed to confirm these results, it is possible that mycotoxins contribute to child growth impairment via mechanisms other than disrupting children's intestinal function.

Gut–brain Axis: Impact of Intestinal Inflammation and Micronutrient Deficiency on Psychomotor Development and Cognitive Functions in Egyptian Children with UndernutritionGut–brain Axis: Impact of Intestinal Inflammation and Micronutrient Deficiency on Psychomotor Development and Cognitive Functions in Egyptian Children with Undernutrition

Cognitive impairment, growth faltering and stunting are pervasive in many countries. mostly causes are unknown. Role of intestinal inflammation in such cases should be minded especially in low- and middle-income countries. We assessed serum markers of inflammation, fecal markers of intestinal inflammation and serum micronutrients in cases with aged 1 to 10 years who suffer from moderate or severe malnutrition “weight-for-age z-score and height-for-age z- Score (WAZ or HAZ) less than -2 SD”. Cognitive abilities were assessed using Wechsler intelligence scale for preschool and school children, Bayley scale III. 55.6% of preschool cases were below average or had mild or moderate intelligence retardation while 24.5% of school cases and 5% of children below 2 years were below average regarding cognitive functions. Cases showed statistically significant reduction of vitamin D, zinc and iron as compared to control. Serum markers of inflammation (alpha 1- glycoprotein (a1-AGP), endotoxin core protein (EndoCAB)) and fecal markers of intestinal inflammation (alpha 1 antitrypsin (AAT) and neopterin (NEOP)) were significant higher in cases than controls. School children showed negative correlation between processing functions and( a1-AGP), positive correlation between perceptual reasoning and serum vitamin A. Children below 2 years, showed negative correlations between motor function and (AAT), (a1-AGP), tumor necrosis factor- alpha (TNF-a) and (EndoCAB), positive correlation between language and serum zinc. In conclusion, our study showed impaired neurocognitive and psychomotor functions in malnourished stunted children. Also, vitamins and minerals deficiency and increased markers of intestinal inflammation were observed in cases compared to healthy control.

Inadequate Vitamin C Intake and Intestinal Inflammation Are Associated with Multiple Micronutrient Deficiency in Young Children: Results from a Multi-Country Birth Cohort Study.

Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex [OR: 0.72, 95% CI: 0.54, 0.92]. A greater risk of MMD was associated with lower vitamin C intake [OR: 0.70, 95% CI: 0.48, 0.94] and increased fecal concentrations of MPO [OR: 1.31, 95% CI: 1.08, 1.51]. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.

Clinical Study On the Relationship Between Neopterin and Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a reproductive endocrine and metabolic disorder. To offer new research direction for polycystic ovary syndrome (PCOS), including its pathogenesis and treatment, this research explores the relationship between neopterin (NPT) and polycystic ovary syndrome. 40 cases with PCOS were selected in the reproductive medicine clinics of the Second Affiliated Hospital of Shandong First Medical University as PCOS group from January 2017 to December 2018. 40 cases with normal pregnancy plan were treated as non-PCOS group, whose menstruation is from 25 days to 35 days. We divided the two groups into two subgroups separately according to their body mass index (BMI): the obese one with BMI≥25kg/m2and non-obese one with BMI&lt;25kg/m2 . The expression levels of triglycerides (TG), total cholesterol (TC), fasting insulin (FINS), C-reactive protein (CRP), neutrophil (N), NPT and interleukin-6 (IL-6) in PCOS group were higher than non-PCOS group. CRP, NPT and IL-6 in the obese group were increased than the non-obese group in the pairwise comparison of its subgroups whether in PCOS group or non-PCOS group. In the analysis of linear correlation, NPT was positively correlated with TG, TC, WBC, N, CRP, FINS, IL-6 and TNF-α (P&lt;0.01). Multivariate Stepwise regression analysis found that FINS and IL-6 was the two most important factors. The expression of NPT in PCOS patients was higher than nonPCOS. NPT maybe play a significant role in the development of PCOS

Diagnostic and Predictive Significance of Acute Phase Response and Neopterin Levels in Lame Racing Dromedary Camels (Camelus dromedarius)

The lameness of racing camels is a major health concern and a financial burden for many camel owners. This study was aimed to investigate different acute phase proteins, cytokines (CYTs), and neopterin (NPT) in the blood of racing lamed camels to highlight their role in disease diagnosis, pathogenesis and monitor treatment response. A 35 out of 315 racing camels exhibited clinical lameness. The mean serum levels of serum amyloid A (SAA) and CYTs (TNF-α, IL-1α, IL-1β, and IL-6) in lame dromedary camels with different detected causes (punctured foot and traumatic injury) were remarkably over than those detected in control healthy dromedary camels. It was found that lame dromedary camels had non-significant changes in serum levels of haptoglobin (HP) and NPT when compared with control healthy camels. A dramatic decline was detected in serum levels of SAA and CYTs of lame camels after 10 days of treatment whereas, the levels of HP and NPT remain at the same levels without any significant changes. The ROC curves were created for the tested biomarkers. The AUCs were calculated to evaluate each variable’s accuracy to differentiate diseased from healthy camels. Based on the ROC curves and AUCs, both the SAA and CYTs provide similar and highly accurate diagnostic accuracy (AUC > 0.8) and monitoring of lameness treatment response.

Oxidative stress, ceruloplasmin and neopterin biomarkers in dromedary camels with clinical endometritis.

The purpose of this study is to investigate the role of some oxidative stress (OS), ceruloplasmin (Cp), and neopterin (NPT) as diagnostic biomarkers for dromedary camels endometritis as well as to explore the impact of ceftiofur treatment on endometritis. Camels were categorized into two groups; healthy control group (n = 20) and endometritis group (n = 60). She-camels with clinical signs of endometritis (CE) received 6.6 mg/kg BW of ceftiofur (i/m). On days 7, and 14, she-camels were evaluated and clinical cure or failure to cure was determined. The comparison of the groups for OS demonstrated that endometritis caused an increase in serum malondialdehyde (sMDA), Cp, and NPT levels (P<0.05), but decreased serum levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.05). The most prevalent pathogens involved in the etiology of CE are Arcanobacterium pyogenes, Streptococcus pyogenes, and Staphylococcus aureus. All examined biomarkers demonstrated a high degree of recognition between CE camel and healthy controls (the area under the curve (AUC) was 95.9 for NPT). A higher proportion of camels with CE that were treated with ceftiofur (90%, P<0.0001) showed clinical cure by the first dose, while 10% required a second dose. In conclusion, CE causes increased oxidative reactions and decreased antioxidant defense competence. Subsequently, the alteration in that balance that was represented by the biomarkers of OS could be beneficial for clinical practice and basic clinical research. Additionally, all trials demonstrated the efficacy of ceftiofur for the treatment of CE in she-camel.

Role of Clinical Characteristics and Biomarkers at Admission to Predict One-Year Mortality in Elderly Patients with Pneumonia.

Background: A hospitalization for community-acquired pneumonia results in a decrease in long-term survival in elderly patients. We assessed biomarkers at admission to predict one-year mortality in a cohort of elderly patients with pneumonia. Methods: A prospective observational study included patients >65 years hospitalized with pneumonia. Assessment of PSI, CURB-65, and biomarkers (C-reactive protein (CRP), procalcitonin (PCT), NT-pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-6 and -8, tumor necrosis factor alpha (TNF-α), serum amyloid A (SAA), neopterin (NP), myeloperoxidase (MPO), anti-apolipoprotein A-1 IgG (anti-apoA-1), and anti-phosphorylcholine IgM (anti-PC IgM)) was used to calculate prognostic values for one-year mortality using ROC curve analyses. Post hoc optimal cutoffs with corresponding sensitivity (SE) and specificity (SP) were determined using the Youden index. Results: A total of 133 patients were included (median age 83 years [IQR: 78–89]). Age, dementia, BMI, NT-proBNP (AUROC 0.65 (95% CI: 0.55–0.77)), and IL-8 (AUROC 0.66 (95% CI: 0.56–0.75)) were significantly associated with mortality, with NT-proBNP (HR 1.01 (95% CI 1.00–1.02) and BMI (HR 0.92 (95% CI 0.85–1.000) being independent of age, gender, comorbidities, and PSI with Cox regression. At the cutoff value of 2200 ng/L, NT-proBNP had 67% sensitivity and 70% specificity. PSI and CURB-65 were not associated with mortality. Conclusions: NT-proBNP levels upon admission and BMI displayed the highest prognostic accuracy for one-year mortality and may help clinicians to identify patients with poor long-term prognosis.

Assessment of Serum Neopterin as a Biomarker in Peripheral Artery Disease.

Neopterin (NPT), a pyrazino-pyrimidine compound mainly produced by activated macrophages, has been regarded as a proinflammatory and proatherosclerotic agent. The study was designed to evaluate NPT level and its interaction with conventional peripheral artery disease (PAD) biomarkers and vascular regenerative potential in severe PAD. The study included 59 patients (females n = 17, males n = 42) aged 67.0 ± 8.2 years classified into two groups based on ankle-brachial index (ABI) measurements (ABI ≤ 0.9 n = 43, ABI ≤ 0.5 n = 16). A total of 60 subjects aged 70.4 ± 5.5 years (females n = 42, males n = 18) with ABI > 0.9 constituted a reference group. NPT concentration reached values above 10 nmol/L in patients with PAD, which differed significantly from reference group (8.15 ± 1.33 nmol/L). High levels of CRP > 5 mg/L, TC > 200 mg/dL as well as lipoproteins LDL > 100 mg/dL and non-HDL > 130 mg/dL were found in the same group, indicating the relationship between NPT and conventional atherogenic markers. The endothelial progenitor cells (EPCs) tended toward lower values in patients with ABI ≤ 0.5 when compared to reference group, and inversely correlated with NPT. These findings indicate a crucial role of NPT in atheromatous process and its usefulness in monitoring PAD severity. However, the role of NPT in chronic PAD needs further studies including relatively high number of subjects.

Assessment of Neopterin Serum Level for Monitoring Therapy of Patients with Mycobacterium tuberculosis

Background: Tuberculosis (TB) is a major health problem worldwide. To date, the standard diagnostic method for TB is still the direct observation of Mycobacterium TB in a sputum smear or culture. Objectives: There is an urgent need for a method to detect the disease in a shorter time with acceptable sensitivity and specificity and help monitor the treatment. Methods: A panel of 34 adults newly diagnosed with smear-positive pulmonary TB was followed during their treatment period of five months. Neopterin (NPT) serum levels were measured three times (before treatment and two and five months after treatment) using the Brahms ELItest Neopterin kit, and the results were analyzed using descriptive and graphical methods. Results: The mean NPT for the first time before treatment was 27.47 ± 20.7 nmol/L. NPT was measured two months after the anti-TB treatment, and the associated mean was 16.97 ± 14.14 nmol/L. At the end of the fifth month, the mean NPT concentration reached 11.3 ± 10.5 nmol/L. The mean serum NPT before treatment had a statistically significant difference with the mean NPT at the end of the second and fifth months of the treatment (P = 0.001). Conclusions: According to the national protocol for treating TB, a sputum smear is still necessary for patients’ follow-up. It seems that the serum NPT level should be measured to monitor response to treatment in patients that, for any reason are not able to give sputum in TB treatment follow-up.

The potential role of neopterin in Covid-19: a new perspective.

Neopterin (NPT) is a member of pteridines group, synthesized by macrophages when stimulated by interferon gamma (INF-γ). NPT is regarded as a macrophage stimulation indicator, marker of cellular immune activation and T helper 1 (Th1) type 1 immune response. Here, we aimed to provide a view point on the NPT features and role in Covid-19. Serum NPT level is regarded as an independent prognostic factor for Covid-19 severity, with levels starting to increase from the 3rd day of SARS-CoV-2 infection, being associated with severe dyspnea, longer hospitalization period and complications. Also, early raise of NPT reflects monocytes/macrophages activation before antibody immune response, despite the NPT level may also remain high in Covid-19 patients or at the end of incubation period before the onset of clinical symptoms. On the other hand, NPT attenuates the activity of macrophage foam cells and is linked to endothelial inflammation through inhibition of adhesion molecules and monocytes migration. However, NPT also exerts anti-inflammatory and antioxidant effects by suppressing NF-κB signaling and NLRP3 inflammasomes. NPT can be viewed as a protective compensatory mechanism to counterpoise hyper-inflammation, oxidative stress, and associated organ damage.

Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone

ABSTRACTBackgroundEnvironmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified.ObjectivesThe objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes.MethodsIn a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations.ResultsThe 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (β: –0.08; 95% CI: –0.14, –0.02) and WLZ (β: –0.03; 95% CI: –0.06, –0.01) were negatively associated with GI score. A high GD score (β: 0.36; 95% CI: 0.08, 0.64) and low AAT (β: –1.35; 95% CI: –2.35, –0.36) were associated with recovery from MAM.ConclusionsScores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.

Iodine Status and Association With Gut Health: A Multi-Site Birth Cohort Study in Eight Low- and Middle-Income Countries

Objectives(To 1) describe trends of iodine status among infants from 6–24 mos old and (2) assess associations between iodine status, intestinal permeability, and inflammation from 6–15 mos old. MethodsData from 1565 children enrolled in the MAL-ED birth cohort were included in these analyses from eight sites (Dhaka, Bangladesh (BGD); Fortaleza, Brazil (BRF); Vellore, India (INV); Bhaktapur, Nepal (NEB); Loreto, Peru (PEL); Naushero Feroze, Pakistan (PKN); Venda, South Africa (SAV); and Haydom, Tanzania (TZH)) from enrolment (≤17 d old) to 24 mos old. Urinary iodine concentration (UIC) was measured at 6, 15, and 24 mos of age using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed via fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1-anti-trypsin (AAT) concentrations (monthly in first year and quarterly in second) and the lactulose-mannitol (LM) test (3, 6, 9, 15 mos). The mean of fecal biomarkers available up to 94 days (interquartile range: 92–120) preceding the iodine quantification were used. LM values used were contemporary to the iodine sampling (6 and 15 mos). Frequency of household use of iodized salt (I-salt) was recorded. A multinomial regression analysis was used to assess classified UIC (deficiency or excess). ResultsI-salt was used in four sites (BGD, BRF, NEB and PEL), but used by fewer than 20% of families in the others. At 6 mos, all sites had adequate (≥100 mg/L) to excess (≥371 mg/L) median UIC. INV had the lowest median UIC (204 μg/L [95%:171–238]) and NEB had the highest (893 μg/L [95%:762–1026]). Between 6–24 mos, five sites displayed a significant decline in the infant’s median UIC (BRF, BGD and SAV sites were constant). An increase of NEO concentration and LM ratio by + 1 sd were found to reduce the odds of high UIC by 0.87 [95%:0.78–0.96] and 0.88 [95%:0.79–0.98] respectively. ConclusionsExcess UIC was predominant at 6 mos and tended to normalize at 24 mos. Aspects of gut inflammation and increased permeability appear to be protective against high UIC in children aged 6–15 mos. Programs addressing iodine-related health should consider the use and appropriate formulation of I-salt and the role of gut permeability in vulnerable individuals. Funding SourcesThe MAL-ED study was supported by the Bill & Melinda Gates Foundation, with grants to the Foundation for the NIH and NIH/FIC.

The effect of staphylococcal mastitis including resistant strains on serum procalcitonin, neopterin, acute phase response and stress biomarkers in Holstein dairy cows.

Staphylococcal mastitis (SM) is a frequent disease in the dairy cattle that is costly to treat. This study aimed to investigate the alterations in the levels of procalcitonin (PCT), neopterin (NPT), haptoglobin (HP), serum amyloid A (SAA), proinflammatory cytokines (IL-1β, IL-8, TNF-α, IF-γ) and oxidative stress (OS) biomarkers in Holstein dairy cows with SM under field conditions. In addition, we also evaluated the role of examined biomarkers in disease pathogenesis and their use as diagnostic biomarkers for the disease in dairy cows. Fifty-three dairy cows with SM, including those with infections caused by Staphylococcus aureus (n = 42) and methicillin resistant S. aureus (MRSA) (n = 11) were selected for this study. In addition, 20 healthy dairy cows were enrolled as a control group. Higher serum levels of PCT, NP, IL-1β, IL-8, TNF-α, IF-γ, HP and SAA and a state of OS was detected in SM group in comparison with the controls. Moreover, the levels of all examined biomarkers in mastitic cows with S. aureus when compared with those infected with MRSA was not significantly different. All examined biomarkers demonstrated a significant degree of discrimination between SM cows and healthy controls (the area under the curve (AUC) ranged from 83.6 for SAA to 100 for PCT). Our study showed that SM in dairy cows was associated with substantial changes in serum PCT, NPT, Acute phase proteins (APPs), proinflammatory cytokines, and OS levels. This study demonstrates that clinical examination in tandem with quantification of PCT, NPT, APPs and cytokines, OS biomarkers could be a useful assessment tool for SM in dairy cows.

Association between vascular endothelial dysfunction and the inflammatory marker neopterin in patients with classic congenital adrenal hyperplasia

Background and aimsPatients with congenital adrenal hyperplasia (CAH) are at increased risk of cardiometabolic abnormalities. We aimed to evaluate vascular endothelial dysfunction and its association with serum neopterin (NP) levels in CAH patients. MethodsThe study included 40 patients, with a mean age of 14.8 ± 2.6 years; 28 (70%) subjects were females. They were compared with 40 healthy controls matched in anthropometric evaluation and measurement of fasting lipids, glucose, insulin, homeostasis model assessment for insulin resistance [HOMA-IR], and serum NP levels (nmol/L). Vascular ultrasound was used to measure brachial artery flow-mediated dilation (FMD%) and carotid intima-media thickness (CA-IMT). According to the degree of control on medical treatment, patients were classified into poor (n = 12) and good (n = 28) control groups. ResultsCompared to controls, CAH patients had lower brachial FMD% (4.60 ± 2.13 versus 9.31 ± 2.29, p = 0.001), similar CA-IMT (0.44 ± 0.08 versus 0.44 ± 0.06, p = nonsignificant) and higher NP (42.6 ± 11.6 versus 9.2 ± 3.8, p = 0.001). However, differences between poor and good control CAH patients were significant regarding FMD%, CA-IMT, and NP measurements. FMD% correlated significantly with NP (r = −0.54, p = 0.001), high-sensitivity CRP (r = −0.53, p = 0.001), HOMA-IR (r = −0.31, p = 0.01), CA-IMT (r = −0.22, p < 0.05), diastolic blood pressure (r = 0.32, p = 0.01) and systolic blood pressure (r = −0.22, p < 0.05). NP was the most significant independent predictor of FMD%, as determined by linear regression analysis (p = 0.001). ConclusionsOur study showed that CAH patients had endothelial dysfunction, which is an early process of vascular affection. This was significantly associated with NP levels, suggesting a crucial role of inflammation in the pathogenesis of vascular damage. Further studies are needed to confirm our findings and to investigate the exact role of NP, as either protective or proatherothrombotic.

Selected biochemical parameters in the urine of HIV-infected patients in monitoring of kidney function.

For years, there has been an increase in the number of cases of chronic kidney disease (CKD) in human immunodeficiency virus (HIV)-infected patients. Renal dysfunction can be caused by direct effects of HIV on the kidneys but also of applied combined antiretroviral therapy (cART). Therefore there is a need of renal function diagnosis to monitor the development of kidney disturbances. In this study the urinary levels of selected low molecular weight proteins (LMWP) in HIV-infected patients were measured and related to current CD4+ T lymphocyte (LT CD4+) count, the glomerular filtration rate (eGFR) value and the applied cART. The levels of 5 LMWP - kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), glutathione S-transferase α (GST-α) and π (GST-π) isoenzymes and neopterin (NPT) - in urine were measured in HIV-infected patients and healthy controls by enzyme-linked immunosorbent assay. Taking into account the current LT CD4+ count, KIM-1, NGAL and GST-α showed statistically significant differences between groups with the CD4+ count < 500 and ≥ 500 cells (< 0.001). Depending on the eGFR, apart from KIM-1 and NGAL, NPT showed statistically significant differences in the investigated groups with normal and lower eGFR values (< 0.001). In terms of applied cART, the best parameters in the assessment of kidney damage were NGAL, GST-π and NPT (< 0.001). This research shows that the analyzed LMWP parameters are useful in the assessment of kidney damage in HIV patients during cART, especially NPT, NGAL and GST-π. However, future studies should be conducted on larger groups.