Intracellular neutrophil myeloperoxidase level in pediatric patients: significant age and gender variability

Nikulshin, Sergey; Tolstikova, Iveta; Bartule, A.; Kviluna, Daiga; Grāvele, Dagne; Gardovska, Dace

doi:10.1111/ijlh.12252

Cited by 13 publications

(17 citation statements)

References 15 publications

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“…We have shown that MPO activity in the blood neutrophils of women with abnormal menstrual cycles is significantly lower than in neutrophils of women with normal menstrual cycles, although neutrophil counts are similar between women with abnormal menstrual cycles and those with normal menstrual cycles. Mean peroxidase index in women with abnormal menstrual cycles (mean: −0.54) was consistent with the values in girls aged ≤17 years (median: 0.0) and in postmenopausal women (mean: −1.84) . These findings may indicate that MPO activity in blood neutrophils is decreased in women who have a few ovulatory cycles, such as girls, women with abnormal menstrual cycles, and postmenopausal women.…”

Section: Discussionsupporting

confidence: 77%

“…Mean peroxidase index was calculated as follows:

MPXI = [(mean neutrophil region MPO - expected staining index) / expected staining index] \times 100

. Here, mean neutrophil region MPO is the absorbance measurement in the neutrophil region; Expected staining index is the expected MPO level for a standard neutrophil population . Although Neut X and MPXI are not currently common measurements in clinical practice, MPXI has been useful in clinical settings for conditions such as systemic inflammatory response syndrome and bacterial infection .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age

Shibata

Sakamoto

Osaka

et al. 2016

Int J Lab Hematology

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Section: Discussionsupporting

confidence: 77%

“…Mean peroxidase index was calculated as follows:

MPXI = [(mean neutrophil region MPO - expected staining index) / expected staining index] \times 100

Section: Methodsmentioning

confidence: 99%

Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age

Shibata

Sakamoto

Osaka

et al. 2016

Int J Lab Hematology

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“…In spite of a good correlation of fecal myeloperoxidase with laboratory and endoscopic parameters of inflammation [77], recent breastfeeding is also associated with increased fecal levels [30]. Furthermore, gender differences, with lower intracellular neutrophil myeloperoxidase levels in boys, have been reported [78]. Neopterin, an indicator of T-helper cell 1 activity, is used as a biomarker of intestinal inflammation [28,30,39,40].…”

Section: Fecal Biomarkersmentioning

confidence: 99%

Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of São Tomé Island

Garzón

Pereira‐da‐Silva

Seixas

et al. 2017

Pathogens and Global Health

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The cumulative effect of repeated asymptomatic enteric infections on intestinal barrier is not fully understood in infants. We aimed to evaluate the association between previous enteric parasitic infections and intestinal inflammation and permeability at 24-months of age, in asymptomatic infants of São Tomé Island. A subset of infants from a birth cohort, with intestinal parasite evaluations in at least four points of assessment, was eligible. Intestinal inflammatory response and permeability were assessed using fecal S100A12 and alpha-1-antitrypsin (A1AT), respectively. The cutoff <-1SD for weight-for-length and length-for-age was used to define wasting and stunting. Multivariable linear regression analysis explored if cumulative enteric parasitic infections explained variability of fecal biomarkers, after adjusting for potential confounders. Eighty infants were included. Giardia duodenalis and soil-transmitted helminths (STH) were the most frequent parasites. The median (interquartile range) levels were 2.87 μg/g (2.41-3.92) for S100A12 and 165.1 μg/g (66.0-275.6) for A1AT. Weak evidence of association was found between S100A12 levels and G. duodenalis (p = 0.080) and STH infections (p = 0.089), and between A1AT levels and parasitic infection of any etiology (p = 0.089), at 24-months of age. Significant associations between A1AT levels and wasting (p = 0.006) and stunting (p = 0.044) were found. Previous parasitic infections were not associated with fecal biomarkers at 24 months of age. To summarize, previous asymptomatic parasitic infections showed no association with intestinal barrier dysfunction. Notwithstanding, a tendency toward increased levels of the inflammatory biomarker was observed for current G. duodenalis and STH infections, and increased levels of the permeability biomarker were significantly associated with stunting and wasting.

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“…This sex effect was not mentioned in previous AZD3241 study reports. However, previous studies in which impact of myeloperoxidase activity on neurodegenerative disease was investigated have reported sex as an important risk factor in myeloperoxidase expression. This result suggests that a sex‐related difference should potentially be considered in future clinical development of AZD3241.…”

Section: Discussionmentioning

confidence: 95%

Population Pharmacokinetic Modeling With Enterohepatic Circulation for AZD3241 in Healthy Subjects and Patients With Multiple System Atrophy

Tong

Zhou

Savage

et al. 2018

The Journal of Clinical Pharma

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AZD3241 is a potent and selective myeloperoxidase inhibitor potentially for the treatment of a number of neurodegenerative disorders, including multiple system atrophy (MSA). The objectives of this work were to develop a population pharmacokinetic (PopPK) model for AZD3241 and to investigate the correlation between AZD3241 exposure and myeloperoxidase inhibition. The PopPK model was developed using AZD3241 data from one phase 1 study in healthy subjects and one phase 2 study in patients with MSA. A one-compartment model incorporating a gallbladder compartment for enterohepatic circulation, sequential zero-first order absorption, and first-order elimination adequately described the AZD3241 concentration profiles. The apparent clearance and central volume of distribution were 63.1 L/h (interindividual variability: 34.8%) and 121.9 L (interindividual variability: 44.0%), respectively. The enterohepatic circulation model reasonably captured the second peak of AZD3241, and high-fat food increased the absorption rate by 69%. A linear regression model was applied to describe the relationship between AZD3241 exposure and percentage change from baseline in myeloperoxidase-specific activity. The developed PopPK model was consistent with known pharmacokinetic characteristics of AZD3241. This model can be used to estimate AZD3241 exposure in patients with MSA and could be applied to future pharmacokinetic-pharmacodynamic analyses of AZD3241 in clinical development.

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Intracellular neutrophil myeloperoxidase level in pediatric patients: significant age and gender variability

Cited by 13 publications

References 15 publications

Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age

Myeloperoxidase in blood neutrophils during normal and abnormal menstrual cycles in women of reproductive age

Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of São Tomé Island

Population Pharmacokinetic Modeling With Enterohepatic Circulation for AZD3241 in Healthy Subjects and Patients With Multiple System Atrophy

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