Construction of a Zn(II)-Eu(III) Nanoring with Temperature-Dependent Luminescence for the Qualitative and Quantitative Detection of Neopterin as an Inflammatory Marker.

A nine-metal Zn(II)-Eu(III) nanoring 1 with a diameter of about 2.3 nm was constructed by the use of a long-chain Schiff base ligand. It shows a luminescence response to neopterin (Neo) through the enhancement of lanthanide emission with high selectivity and sensitivity, which can be used to quantitatively analyze the concentrations of Neo in fetal calf serum and urine. The luminescence sensing of 1 to Neo is temperature-dependent, and it displays more obvious response behavior at lower temperatures. Filter paper strips bearing 1 can be used to qualitatively detect Neo by the color change from chartreuse to red under a UV lamp. The limit of detection is as low as 3.77 × 10-2 nM.

Fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24-59 months in east Dembiya district, northwest Ethiopia.

BACKGROUND: Environmental enteric dysfunction is a subclinical intestinal disorder characterized by gut inflammation accompanied by morphological changes, such as blunted villi and crypt hyperplasia. This is a common illness in low and middle-income countries. However, environmental enteric dysfunction evidence is limited in Ethiopia. Accordingly, this study was conducted to measure fecal biomarkers of environmental enteric dysfunction and associated factors among children aged 24-59 months in rural northwest Ethiopia. METHODS: A community-based cross-sectional study was employed among 235 randomly selected children in a rural setting of the east Dembiya district. Stool samples were collected without fixative and analyzed for fecal biomarkers of environmental enteric dysfunction (Alpha-1-antitrypsin, neopterin, and myeloperoxidase) using commercial enzyme-linked immunosorbent assay kits and analyzed for intestinal parasites using wet mount and Kato-Katz techniques. Child behaviors related with exposure to enteropathogens, condition of the living environment and socio-demographic information were collected using interviewer-administered questionnaire and structure observation. We fitted multivariable linear regression model to assess the association between environmental factors and concentration of fecal biomarkers of environmental enteric dysfunction in the stool. Statistically significant associations were declared based on adjusted betas with the corresponding 95% confidence interval and p-value < 0.05. RESULTS: The median concentration of fecal markers of environmental enteric dysfunction was 350 µg/ml for Alpha-1-antitrypsin, 3320.2 ng/ml for myeloperoxidase, and 1562 nmol/l for neopterin. The median concentration of Alpha-1-antitrypsin among 161 (68.5%), myeloperoxidase among 168 (71.5%), and neopterin among 188 (80%) of the stool samples were above the normal values in non-tropical settings. Moreover, 100 (42.6%) of the children had high EED disease activity score (above the median score). The elevated concentrations of fecal biomarkers of gut inflammation and the high EED disease activity score were significantly associated with open defecation practice, mouthing of soil contaminated materials, Escherichia coli (E. coli)  contamination of drinking water, E. coli contamination of foods, E. coli contamination of soil, and intestinal parasites. CONCLUSION: Overall, Alpha-1-antitrypsin, myeloperoxidase, and neopterin levels among the children in the studied region were highly elevated in comparison to populations in high-income countries. Moreover, the EED disease activity score in significant proportion of children was high, suggesting widespread intestinal inflammation and increased intestinal permeability. Extensive E. coli contamination of the living environment (drinking water, ready-to-eat foods, and courtyard soil), hygiene and sanitation behaviors (such as open defecation and mouthing of soil contaminated materials), and a high burden of intestinal parasites were identified as factors associated with the elevated concentration of fecal biomarkers of environmental enteric dysfunction. Parental care to children to avoid mouthing of soil contaminated materials and other risky behaviors that increase exposure enteric infections, and protecting the living environment (water, food and soil) from fecal contamination are important.

Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review.

Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates. We performed a systematic literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). We evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty-five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs -21, -19b, and -92a, RNU2-1f, CXCL13, interleukins -6, -8, and -10, soluble interleukin-2-receptor, soluble CD19, soluble CD27, tumour necrosis factor-alfa, beta-2-microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA-21 soluble CD27, and beta-2-microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL-13, beta-2-microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessing the Effectiveness of Selected Biomarkers in the Acute and Cumulative Physiological Stress Response in Professional Rugby Union through Non-invasive Assessment.

Rugby union is a sport involving high force and frequency impacts making the likelihood of injury a significant risk. The aim of this study was to measure and report the individual and group acute and cumulative physiological stress response during 3 professional rugby games through non-invasive sampling. 24 professional rugby players volunteered for the study. Urine and saliva samples were collected pre and post 3 matches. Myoglobin, salivary immunoglobulin A, cortisol, neopterin and total neopterin (neopterin+7,8-dihydroneopterin) were analysed by high performance liquid chromatography or enzyme linked immunosorbent assay. Significant increases in cortisol, myoglobin, neopterin and total neopterin when urine volume was corrected with specific gravity were observed (p<0.05). Significant decreases in salivary immunoglobulin A concentration were observed for games 1 and 2 while secretion rate decreased after games 2 and 3. Significant decreases were seen with the percent of 7,8-dihydroneopterin being converted to neopterin following games 2 and 3. The intensity of 3 professional rugby games was sufficient to elicit significant changes in the physiological markers selected for our study. Furthermore, results suggest the selected markers not only provide a means for analysing the stress encountered during a single game of rugby but also highlight the unique pattern of response for each individual player.

Interleukin-6 and neopterin levels in the serum and saliva of patients with Lichen planus and oral Lichen planus.

BACKGROUND: Lichen planus together with its oral variant is a chronic, inflammatory disease of the skin and the mucosa of unclear aetiology and with an unpredictable course that still poses a major problem in terms of diagnosis and treatment. The objective of this study was to assess the concentrations of interleukin-6 (IL-6) and neopterin in saliva and serum of patients with lichen planus (including reticular and erosive form of oral lichen planus) and to compare them with the concentrations observed in healthy controls. METHODS: The study material comprised serum and saliva samples from 56 patients diagnosed with lichen planus and 56 healthy volunteers. The ELISA test was used to measure concentrations of IL-6 and neopterin in the serum and saliva of the study participants. RESULTS: The concentrations of IL-6 in saliva and serum of patients with lichen planus were significantly higher than in controls (P = 0.0002; P < 0.0001). The difference remains significant after adjustment for gingivitis and age. Patients with atrophic-erosive oral lichen planus had significantly higher IL-6 concentrations in their saliva compared to patients with reticular form of disease (P = 0.01). The concentrations of neopterin were significantly higher in the serum but not in saliva of lichen planus patients vs. controls (P <0.0001). CONCLUSIONS: Serum levels of proinflammatory cytokines IL-6 and neopterin are increased in lichen planus as well as the salivary concentrations of IL-6. The differences observed in IL-6 levels in patients with erosive-atrophic forms of oral lichen planus may indicate a substantial role played by the cytokine in the disease.

Composition and Properties of Saliva in Patients with Osteoporosis Taking Antiresorptive Drugs.

The aim of this study was to examine how the composition and properties of saliva change in people with osteoporosis who have received antiresorptive (AR) treatment, compared to patients with osteoporosis who have not yet received this treatment. METHODS: The study population consisted of 38 patients with osteoporosis using AR drugs (Group I) and 16 patients with osteoporosis who had never used AR drugs (Group II). The control group consisted of 32 people without osteoporosis. Laboratory tests included determination of pH and concentrations of Ca, PO4, total protein, lactoferrin, lysozyme, sIgA, IgA, cortisol, neopterin, activity of amylase at rest, and stimulated saliva. The buffering capacity of stimulated saliva was also determined. RESULTS: There were no statistically significant differences between the saliva of Group I and Group II. No statistically significant correlation was found between the amount of time using AR therapy (Group I) and the tested parameters of the saliva. Significant differences were found between Group I and the control group. The concentrations of PO4, lysozyme, and cortisol were higher, while concentrations of Ca ions, sIgA, and neopterin were lower, in comparison to the control group. The significant differences between Group II and the control group were smaller, and they concerned only the concentrations of lysozyme, cortisol, and neopterin. CONCLUSIONS: The saliva of people with osteoporosis subjected to AR therapy and those not subjected to AR therapy did not show statistically significant differences in terms of the examined parameters of the saliva. However, the saliva of patients with osteoporosis taking and not taking AR drugs was significantly different compared to the saliva of the control group.

Intramuscular interferon beta-1a is effective in Japanese patients with relapsing-remitting multiple sclerosis: a pre-treatment versus treatment comparison study of gadolinium-enhanced MRI brain lesions.

BACKGROUND AND OBJECTIVE: Interferon beta (IFNß) is standard therapy for multiple sclerosis (MS). The efficacy of intramuscular (IM) IFNß-1a (AVONEX(®)) was assessed in 25 Japanese patients with relapsing-remitting MS (RRMS). METHODS: Patients with RRMS not previously treated with IFNß or other disease-modifying therapies were included in this 36-week study. The primary outcome was the average total number of gadolinium-enhanced lesions detected on four brain MRI scans during the last 12 weeks of 24 weeks' treatment with IM IFNß-1a 30 µg once weekly compared with the number during the 12-week pre-treatment period. Lesions were counted by blinded investigators. RESULTS: IM IFNß-1a significantly decreased the median number of gadolinium-enhanced lesions from 2.5 to 0.3 (p < 0.0001) compared with pre-treatment values. The median number of new gadolinium-enhanced lesions also decreased significantly from 2.0 to 0.3 (p = 0.0002). Serum neopterin was induced in a manner similar to that observed previously in a Caucasian RRMS population. No new adverse events occurred during the study. CONCLUSION: This first study of IM IFNß-1a in Japanese patients with RRMS demonstrated a level of efficacy similar to that reported in Caucasian patients based on an assessment of pre-treatment and post-treatment gadolinium-enhanced lesions.

Increased yet iron-restricted erythropoiesis in postpartum mothers.

Iron deficiency in the postpartum period is common and associated with impaired quality of life. Interpretation of ordinary laboratory parameters is considered to be simple in postpartum women, as normalization of pregnancy induced physiological changes is assumed to take place in the early postpartum period. We have studied changes in erythrocyte and iron parameters during the first 11 postpartum months. Erythrocyte parameters and iron markers, serum ferritin, and soluble transferrin receptor (sTfR), and an inflammation marker, neopterin, were investigated in healthy mothers 6 weeks (n = 104), 4 months (n = 100), and 11 months (n = 43) after giving birth to a term infant. Healthy nonpregnant and nonlactating women (n = 61) were included as controls. The hemoglobin level increased throughout the first 11 postpartum months and was significantly higher from 4 months on, compared to control women. At all time points, the mothers had significantly lower mean corpuscular volume (MCV) and higher erythrocyte count and percentage of hypochromic erythrocytes. sTfR levels were significantly higher over the whole serum ferritin distribution during the first 4 postpartum months compared to the controls, indicative of an increased cell production. At 6 weeks, postpartum mothers had higher neopterin levels and this was associated with markers of a low iron status, not including sTfR. Substantial changes in erythrocyte and iron parameters were observed in the postpartum period, consistent with an increased, but iron restricted erythropoiesis. The increased erythropoietic activity was reflected in higher sTfR concentrations. Given the vital role for iron in both mothers and infants, further studies are warranted for establishing proper cut off levels for sTfR as an iron marker in postpartum women.

Protein chip for the parallel quantification of high and low abundant biomarkers for sepsis.

We present herein a protein chip for diagnosis of sepsis that combines both a sandwich and a binding inhibition format in order to quantify high (CRP) and low abundant proteins (cytokines, PCT, neopterin) in parallel. Using the combined assay format the lowest detectable concentrations for CRP, IL-6, IL-8, IL-10, TNFα, PCT, and neopterin are 3 mg/L, 15 ng/L, 26 ng/L, 65 ng/L, 40 ng/L, 78 ng/L, and 0.46 µg/L. Four different combined assay formats are tested, using separate or joint incubation steps of analytes and detection antibodies. Yet, low limit of detection (LOD) and short processing time are contradictory: while the combined assay performed in a multistep protocol is extremely sensitive (e.g., the LOD for IL-6 is 15 ng/L), but more time-consuming (4 h), the all-in-one protocol takes only 2.5 h, but suffers from lower sensitivity compared with the multistep protocol (e.g., the LOD for IL-6 is up to 40 times enhanced). Reproducibility is good in both cases (CV 5-20%).

Gender-specific differences in biomarkers responses to acute coronary syndromes and revascularization procedures.

A growing body of gender-related research in coronary artery disease is beginning to gradually elucidate differences between women and men. In patients presenting with acute coronary syndromes (ACS), these sex differences include varying risk factor profiles, accuracy of diagnostic testing, clinical presentations, treatment practices and outcomes. There is also a differential expression of cardiac biomarkers by sex, which remains unexplained. This paper reviews all the available information on the effect of gender on cardiac biomarkers by search of MEDLINE using the terms gender differences, biomarkers, ACS and revascularization procedures. A better understanding of the sex disparities in biomarkers along with all other clinical information is essential to optimal management and patient care in the future.

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

BACKGROUND: Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. METHODS: Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. RESULTS: Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. CONCLUSIONS: Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Salivary neopterin and related pterins: their comparison to those in plasma and changes in individuals.

Neopterin (NP), biopterin (BP) and monapterin (MP) exist in saliva. The physiological role of salivary NP as well as the pathophysiological role of increased NP in the immune-activated state has been unclear. Saliva is a characteristic specimen different from other body fluids. In this study, we analysed salivary NP and related pterin compounds, BP and MP and revealed some of its feature. High-performance liquid chromatography (HPLC) analysis of saliva and plasma obtained from 26 volunteers revealed that salivary NP existed mostly in its fully oxidized form. The results suggested that salivary NP as well as BP would mostly originate from the oral cavity, perhaps the salivary glands, and that salivary NP levels might not reflect those in the plasma. We also found that a gender difference existed in correlations between concentrations of salivary total concentrations of NP (tNP) and BP (tBP). HPLC analysis of saliva obtained from 5 volunteers revealed that the concentrations of salivary tNP as well as tBP fluctuated in an irregular fashion in various individuals. MP, a diastereomer of NP, might have come from oral cavity NP itself or its precursor. These results indicated that the nature of salivary NP might be different from that of NP in the blood or urine.

Urinary neopterin and total neopterin measurements allow monitoring of oxidative stress and inflammation levels of knee and hip arthroplasty patients.

Knee and hip arthroplasty are common surgeries within an aging population. Some data has suggested that knee arthroplasty is more traumatic to the body than hip arthroplasty due to the increased complexity and load bearing nature of the joint. Here, we compare the stress of the two surgeries by measuring urinary neopterin and total neopterin as biomarkers of oxidative stress and inflammation. Urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) levels were analysed in 28 knee and 22 hip arthroplasty patients pre- and post-operatively to determine oxidative stress and inflammation levels. Total neopterin was 31.1% higher with knee arthroplasty (p<0.05). Urinary neopterin was 32.8% higher in the knee arthroplasty group versus hips. The increase in neopterin and total neopterin following a post-surgical decrease in levels was significant in both groups. Levels of neopterin and total neopterin were varied between patients, but all increased following surgery and subsided by day 28. The increased levels of urinary neopterin and total neopterin from knee arthroplasty indicate that knee osteoarthritis and arthroplasty is a more significant trauma to the body than hip osteoarthritis and arthroplasty surgery. This is also shown by faster inflammatory resolution following hip arthroplasty.

Effects of a combined water and sanitation intervention on biomarkers of child environmental enteric dysfunction and associations with height-for-age z-score: A matched cohort study in rural Odisha, India.

Poor water, sanitation and hygiene (WaSH) conditions are hypothesized to contribute to environmental enteric dysfunction (EED), a subclinical condition that may be associated with chronic undernutrition and impaired linear growth. We evaluated the effect of a combined water and sanitation intervention on biomarkers of EED, and then assessed associations of biomarkers of EED with height-for-age z-scores (HAZ), in children under five. We conducted a sub-study within a matched cohort study of a household-level water and sanitation infrastructure intervention in rural Odisha, India, in which we had observed an effect of the intervention on HAZ. We collected stool samples (N = 471) and anthropometry data (N = 209) for children under age 5. We analyzed stool samples for three biomarkers of EED: myeloperoxidase (MPO), neopterin (NEO), and α1-anti-trypsin (AAT). We used linear mixed models to estimate associations between the intervention and each biomarker of EED and between each biomarker and HAZ. The intervention was inversely associated with AAT (-0.25 log µg/ml, p = 0.025), suggesting a protective effect on EED, but was not associated with MPO or NEO. We observed an inverse association between MPO and HAZ (-0.031 per 1000 ng/ml MPO, p = 0.0090) but no association between either NEO or AAT and HAZ. Our results contribute evidence that a transformative WaSH infrastructure intervention may reduce intestinal permeability, but not intestinal inflammation and immune activation, in young children. Our study also adds to observational evidence of associations between intestinal inflammation and nutritional status, as measured by HAZ, in young children. Trial Registration: ClinicalTrials.gov (NCT02441699).

Increased Fecal Neopterin Parallels Gastrointestinal Symptoms in COVID-19.

INTRODUCTION: Coronavirus disease (COVID-19) has spread from Wuhan, China, and become a worldwide pandemic. Most patients display respiratory symptoms but up to 50% report gastrointestinal symptoms. Neopterin is a surrogate marker for viral inflammation, and its production by macrophages is driven by interferon-γ. METHODS: We measured fecal neopterin in 37 hospitalized COVID-19 patients not requiring intensive care measures and 22 healthy controls. RESULTS: Fecal neopterin was elevated in stool samples from COVID-19 patients compared with that in samples from healthy controls. Especially, patients reporting gastrointestinal symptoms exhibited increased fecal neopterin values. DISCUSSION: COVID-19 is associated with an inflammatory immune response in the gastrointestinal tract.

Macrophage activity in semen is significantly correlated with sperm quality in infertile men.

The presence of leucocytes within semen has the potential to impair sperm function. Neutrophils and macrophages make up 95% of seminal leucocytes, with both having the ability to damage sperm via the generation of reactive oxygen species, proteases and the induction of apoptosis. Existing cytological techniques for quantifying leucocyte activity within semen (peroxidase, CD45) are less than ideal as they merely count the number of leucocytes, rather than assess their activity. Seminal plasma elastase effectively determines neutrophil activity, yet gives no insight into macrophage activity. Neopterin, a molecule released from activated macrophages, may be a useful marker for macrophage activity in the male reproductive tract. To examine this possibility a total of 63 asymptomatic subjects with male factor infertility and 11 fertile controls provided semen samples for measurement of various inflammatory markers. We were able to confirm for the first time that seminal plasma does indeed contain neopterin and that the levels of this macrophage activity marker are threefold higher in infertile than fertile men. Furthermore, seminal plasma neopterin concentration was significantly correlated with sperm oxidative stress, DNA fragmentation (TUNEL) and apoptosis (Annexin V), making it a useful marker of sperm quality. By contrast, seminal plasma elastase showed no correlation with any marker of sperm quality.

The association between neopterin and acetaminophen-induced nephrotoxicity.

INTRODUCTION: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP-induced nephrotoxicity. MATERIALS AND METHODS: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. RESULTS: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). CONCLUSIONS: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury.

[Comparative significance of the biochemical markers of cell-mediated immunity in the diagnosis of tuberculous pleurisy].

The authors have compared the informative value of the tests determining the activity of adenosine deaminase (ADA) and the levels of interferon-gamma (INF-gamma) and neopterin in the diagnosis of pleural effusions of tuberculous (n = 67) and nontuberculous (n = 30) origin. The equally high diagnostic value has been found in the study of the activities of ADA (94.8%) and INF-gamma, which are markers of lymphocytic cellular immunity. There are great differences in the sensitivity of the neopterin test depending whether tuberculosis is isolated or complicates the course of tuberculosis of the lung or intrathoracic lymph nodes, which may be regarded as a reflection of the different status of macrophageal cellular immunity.

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.