And Α1-acid Glycoprotein Research Articles

Current or recent malaria infection is associated with elevated inflammation-adjusted ferritin concentrations in pre-school children: a secondary analysis of the BRINDA database.

Inflammation and infections such as malaria affect micronutrient biomarker concentrations and hence estimates of nutritional status. It is unknown whether correction for C-reactive protein (CRP) and α1-acid glycoprotein (AGP) fully captures the modification in ferritin concentrations during a malaria infection, or whether environmental and sociodemographic factors modify this association. Cross-sectional data from eight surveys in children aged 6-59 months (Cameroon, Cote d'Ivoire, Kenya, Liberia, Malawi, Nigeria and Zambia; n 6653) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) project were pooled. Ferritin was adjusted using the BRINDA adjustment method, with values < 12 μg/l indicating iron deficiency. The association between current or recent malaria infection, detected by microscopy or rapid test kit, and inflammation-adjusted ferritin was estimated using pooled multivariable linear regression. Age, sex, malaria endemicity profile (defined by the Plasmodium falciparum infection prevalence) and malaria diagnostic methods were examined as effect modifiers. Unweighted pooled malaria prevalence was 26·0 % (95 % CI 25·0, 27·1) and unweighted pooled iron deficiency was 41·9 % (95 % CI 40·7, 43·1). Current or recent malaria infection was associated with a 44 % (95 % CI 39·0, 52·0; P < 0·001) increase in inflammation-adjusted ferritin after adjusting for age and study identifier. In children, ferritin increased less with malaria infection as age and malaria endemicity increased. Adjustment for malaria increased the prevalence of iron deficiency, but the effect was small. Additional information would help elucidate the underlying mechanisms of the role of endemicity and age in the association between malaria and ferritin.

Ross 708 broiler small intestine morphology and immunity improvements in response to in ovo Marek's Disease vaccine administration alone or in conjunction with in ovo and dietary supplemental calcifediol

Investigations were performed to determine the systemic immune and small intestine (SI) morphological responses of Ross 708 broilers to the Marek's Disease vaccine (MDV) administered alone or in conjunction with the in ovo and dietary administration of calcifediol (25OHD3). Live embryonated hatching eggs were assigned at random to 3 in ovo treatments at 18 d of incubation. Pre-specified in ovo treatments were: commercial MDV-alone-injected (50 µL) or commercial MDV containing 1.2 (MDV+25OHD3-1.2) or 2.4 (MDV+25OHD3-2.4) μg of 25OHD3. A non-injected control treatment was also included. For the growing phase, broilers received a commercial diet containing 250 IU of vitamin D3 /kg (control) or a commercial diet supplemented with 2,760 IU of 25OHD3 /kg (Hy-D diet). For determination of serum IgG, nitric oxide, and α-1-acid glycoprotein (AGP) at 14 and 40 d of age (doa), blood was collected from 1 bird per pen (48 total). In the duodenum, jejunum, and ileum of the same bird, villus length (VL), crypt depth (CD), VL to CD ratio (VCR), and villus surface area were also determined. There were no significant dietary x in ovo treatment interactions for any of the variables examined. However, birds fed Hy-D diets had lower serum AGP levels at 14 doa when compared to those fed un-supplemented commercial diets. Additionally, at 40 doa, birds in the MDV+25OHD3-1.2 and MDV+25OHD3-2.4 treatments experienced a decrease in serum AGP in comparison to those belonging to the non-injected and MDV-alone treatment groups. A higher jejunal VCR was observed at 14 and 40 doa in birds that belonged to the MDV+25OHD3-1.2 treatment when compared to those in the non-injected and MDV-alone treatment groups, and dietary Hy-D increased the VL of the duodenum and jejunum in birds at 14 and 40 doa when compared to those fed the commercial diet. In conclusion, both dietary or in ovo administration of 25OHD3 lowered inflammatory reactions and improved the SI morphology of broilers that were in ovo-injected with the MDV.

Protopine and Allocryptopine Interactions with Plasma Proteins

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids, i.e., allocryptopine (ACP) and protopine (PP), was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA’s drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/quinaldine red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged, suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural product–protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

Possible Involvement of Protein Binding Inhibition in Changes in Dexmedetomidine Concentration in Extracorporeal Circuits during Midazolam Use.

It was recently reported that the dexmedetomidine concentration within the extracorporeal circuit decreases with co-administration of midazolam. In this study, we investigated whether displacement of dexmedetomidine by midazolam from the binding site of major plasma proteins, human serum albumin (HSA) and α1-acid glycoprotein (AAG), would increase levels of free dexmedetomidine that could be adsorbed to the circuit. Equilibrium dialysis experiments indicated that dexmedetomidine binds to a single site on both HSA and AAG with four times greater affinity than midazolam. Midazolam-mediated inhibition of the binding of dexmedetomidine to HSA and AAG was also examined. The binding of dexmedetomidine to these proteins decreased in the presence of midazolam. Competitive binding experiments suggested that the inhibition of binding by midazolam was due to competitive displacement at site II of HSA and due to non-competitive displacement at the site of AAG. Thus, our present data indicate that free dexmedetomidine displaced by midazolam from site II of HSA or from AAG is adsorbed onto extracorporeal circuits, resulting in a change in the dexmedetomidine concentration within the circuit.

Deciphering the binding mechanism of gingerol molecules with plasma proteins: implications for drug delivery and therapeutic potential

Ginger is a highly valued herb, renowned globally for its rich content of phenolic compounds. It has been traditionally used to treat various health conditions such as cardiovascular diseases, digestive issues, migraines, Alzheimer’s disease, tumor reduction and chronic inflammation. Despite its potential medicinal applications, the therapeutic effectiveness of ginger is hindered by its limited availability and low plasma concentration levels. In this study, we explored the interaction of ginger’s primary phenolic compounds, specifically 6-gingerol (6 G), 8-gingerol (8 G) and 10-gingerol (10 G), with plasma proteins which are human serum albumin (HSA) and α-1-acid glycoprotein (AGP). These two plasma proteins significantly influence drug distribution and disposition as they are key binding sites for most drugs. Fluorescence emission spectra indicated strong binding of 6, 8 and 10 G with HSA, with binding constants of 2.03 ± 0.01 × 104 M−1, 4.20 ± 0.01 × 104 M−1 and 6.03 ± 0.01 × 106 M−1, respectively. However, the binding of gingerols with AGP was found to be negligible. Molecular displacement by site-specific probes and molecular docking analyses revealed that gingerols bind at the IIA domain, with stability provided by hydrogen bonds, van der Waals forces, conventional hydrogen bonds, carbon-hydrogen bonds, alkyl and Pi–alkyl interactions. Further, the partial unfolding of the protein was observed upon binding the gingerol compound with HSA. In addition, molecular dynamic simulations demonstrated that gingerols remained stable in the subdomain IIA over 100 ns. This stability, coupled with Molecular Mechanics Generalized Born Surface Area indicating free energies of −43.765, −57.504 and −66.69 kcal/mol for 6, 8 and 10 G, respectively, reinforces the robust binding potential of these compounds. Circular dichroism studies suggested that the interaction of gingerols leads to the minimal transformation of HSA secondary structure, with the pattern being 10 G > 8 G > 6 G, a finding further substantiated by root mean square deviation and root mean square fluctuation fluctuations. These results propose that HSA has a stronger affinity to gingerols than AGP, which could have significant implications on the therapeutic circulating levels of gingerols. Communicated by Ramaswamy H. Sarma

In vitro biodistribution studies on clinically approved FGFR inhibitors ponatinib, nintedanib, erlotinib and the investigational inhibitor KP2692

Binding towards human serum albumin (HSA) and α1-acid glycoprotein (AGP) of three approved fibroblast growth factor receptor (FGFR) inhibitors ponatinib (PON), nintedanib (NIN) and erdafitinib (ERD), as well as the experimental drug KP2692 was studied by means of spectrofluorometric and UV–visible spectrophotometric methods. Additionally, proton dissociation processes, lipophilicity, and fluorescence properties of these four molecules were investigated in detail. The FGFR inhibitors were predominantly presented in their single protonated form (HL+) at pH 7.4 (at blood pH). At gastric pH (pH 1–2) the protonated forms (+1 – +3) are present, which provide relatively good aqueous solubility of the drugs. All of the four inhibitors are highly or extremely lipophilic at pH 7.4 (logD7.4 ≥ 2.7). At acidic pH 2.0 PON and ERD are rather lipophilic, NIN is amphiphilic, while KP2692 is highly hydrophilic. All four compounds bind to HSA and AGP. Moderate binding of PON, KP2692 and NIN was found towards albumin (logK’ = 4.5–4.7), while their affinity for AGP was about one order of magnitude higher (logK’ = 5.2–5.7). ERD shows a larger affinity for both proteins (logK’HSA ≈ 5.2, logK’AGP ≈ 7.0). The computed constants were used to model the distribution of the FGFR inhibitors in blood plasma under physiological and pathological (acute phase) conditions. The changing levels of the two proteins under pathological conditions compensate each other for PON and NIN, so that the free drug fractions do not change considerably. In the case of ERD the higher AGP levels distinctly reduce the free available fraction of the drug. Comparison with clinical pharmacokinetic data indicates that the here presented solution distribution studies can very well predict the conditions in cancer patients.

Maternal prenatal, with or without postpartum, vitamin D3 supplementation does not improve maternal iron status at delivery or infant iron status at 6 months of age: secondary analysis of a randomised controlled trial

BackgroundVitamin D may modify iron status through regulation of hepcidin and inflammatory pathways. This study aimed to investigate effects of maternal vitamin D supplementation on iron status in pregnancy and...

Retention Behavior of Anticancer Thiosemicarbazides in Biomimetic Chromatographic Systems and In Silico Calculations.

Chromatographic methods, apart from in silico ones, are commonly used rapid techniques for the evaluation of certain properties of biologically active compounds used for their prediction of pharmacokinetic processes. Thiosemicarbazides are compounds possessing anticancer, antimicrobial, and other valuable biological activities. The aim of the investigation was to estimate the lipophilicity of 1-aryl-4-(phenoxy)acetylthiosemicarbazides, to predict their oral adsorption and the assessment of their % plasma-protein binding (%PPB). RP-HPLC chromatographic techniques with five diversified HPLC systems, including columns with surface-bonded octadecylsilanes (C-18), phosphatidylcholine (immobilized artificial membrane, IAM), cholesterol (Chol), and α1-acid glycoprotein (AGP) and human serum albumin (HSA), were applied. The measured lipophilicity of all investigated compounds was within the range recommended for potential drug candidates. However, some derivatives are strongly bonded to HSA (%PPB ≈ 100%), which may limit some pharmacokinetic processes. HPLC determined lipophilicity descriptors were compared with those obtained by various computational approaches.

Interaction of Blenoxane and Congeners Bleomycins A2 and B2 with Human Plasma Proteins Using Circular Dichroism Spectroscopy.

Bleomycin is a glycopeptide congeners' family of antitumor antibiotics employed for the treatment of several types of tumors such as squamous cell carcinomas and malignant lymphomas. The general chemical structure is constituted by three main portions: (i) a metal binding domain that is recognized to be responsible for the DNA cleavage activity; (ii) a DNA binding domain via the 1-4' bithiazole moiety; and (iii) a carbohydrate domain thought to be responsible for the accumulation of bleomycin in some cancer cells. To date, a limited number of protein interactions with bleomycin have been studied, but the plasma binding has not yet been determined. Here, we explore this aspect of the protein binding capacity of bleomycin to the two most abundant plasma proteins, human serum albumin (HSA) and α1-acid glycoprotein (AGP), which are known to bind and to be carriers of many drug molecules using spectroscopic techniques, such as circular dichroism, UV-vis absorbance, and fluorescence. The results showed that bleomycin binds to plasma proteins with an order-of-magnitude higher affinity for AGP than HSA. This is particularly important as AGP is an acute phase protein and is overexpressed in cancer patients. This should be taken into consideration as it could affect the therapeutic effect of the bleomycin dosage.

Tumor Necrosis Factor (TNF) α, Endothelin (ET) 1 and α1-Acid Glycoprotein (AGP) as Potential Urine and Serum Markers of Metabolic Complications in Psoriasis?

Psoriasis, one of the most frequent dermatoses, strongly associated with metabolic disorders which increase patients' comorbidity and mortality. Hence, it is essential to look for markers of such complications. Our aim was to assess the clinical utility of urinary tumor necrosis factor alpha (TNFα), endothelin 1 (ET-1) and α1-acid glycoprotein (α1AGP) as well as their serum concentrations as markers of metabolic complications in psoriatics, and to examine the relations of these markers to clinical and demographic parameters. The study involved 60 patients with plaque psoriasis and 30 volunteers without skin diseases (the control group). Serum and urinary concentrations of TNFα, ET-1 and α1AGP were measured by ELISA. Psoriasis severity was assessed using the psoriasis activity and severity index (PASI). Routine laboratory investigations were additionally performed. All serum markers were significantly higher in the patients compared to the controls. TNFα was undetectable in the urine in half of the patients. The urinary ET-1/creatinine concentration ratio was significantly lower in the psoriatics than the controls, whereas the absolute urinary α1AGP was significantly higher and the α1AGP/creatinine ratio was insignificantly different. There was no correlation between serum or urinary markers and PASI. All serum markers were higher in patients with psoriasis lasting less than 15years. Serum TNFα, ET-1 and α1AGP seem to be useful biomarkers of metabolic syndrome in psoriatics. ET-1 could perhaps become a urinary marker of metabolic disorders in psoriatics, but further studies are required to confirm that a decreased ET-1 concentration in urine is a reliable predictive tool. Increased urinary α1AGP also requires more in-depth research as a potential marker. TNFα urine assessment does not seem to be useful for screening for metabolic disorders in psoriatics. Serum or urinary TNFα, ET-1 and α1AGP do not seem to be associated with psoriasis severity or duration.

Elucidation of Drug Transport Mechanism by Serum Protein and Development for Pancreatic Cancer Treatment

Human serum albumin (HSA) and α1-acid glycoprotein (AGP) are the major drug-binding proteins in the blood and regulate the tissue transfer of bound drugs. We succeeded in clarifying the three-dimensional structure of AGP for the first time in the world from X-ray crystal structure analysis. Using a site-directed mutagenesis method by constructing yeast expression systems as well as the three-dimensional structure, we elucidated the properties of drug binding sites of AGP. We also found that structural change due to the interaction between AGP and cell membranes causes the release of bound drugs and reported an "AGP-mediated drug transport process." Pancreatic cancer has an extremely low response rate to anticancer drugs compared to other cancers and is resistant to starvation of nutrients including fatty acids. We clarified that glutamine metabolism is involved in this tolerance. Furthermore, aiming at efficient drug delivery and effective treatment for pancreatic cancer, we focused on nitric oxide (NO) which increases pancreatic blood flow and has a cell-killing effect on tumors and surrounding stromal tissues. We successfully synthesized nitrated phenylbutyrate (NPB), which binds to HSA and has an antitumor effect in vitro and vivo. The binding of NPB to HSA is considered to be useful for delivery to tumors through the enhanced permeability and retention (EPR) effect and HSA receptors.

The Effects of One Egg Per Day on Vitamin A Status Among Young Malawian Children: A Secondary Analysis of a Randomized Controlled Trial

BackgroundVitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods. ObjectivesThis analysis aimed to determine the impact of supplementing children’s diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD. MethodsChildren age 6–9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol <0.7 μmol/L) were compared between groups using log-binomial or modified Poisson regression models. ResultsAfter 6 mo of study participation, 489 were assessed for retinol (egg: n = 238; control: n = 251), and 575 (egg: n = 281; control: n = 294) were assessed for RBP. Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 μmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 μmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]. ConclusionsProvision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx.This trial was registered at [clinicaltrials.gov] as [NCT03385252].

Comparison of Total Body Vitamin A Stores Using Individual versus Population 13C-Natural Abundance of Serum Retinol in Preschool Children and Women Residing in 6 Diverse African Countries

BackgroundStable isotope techniques using 13C to assess vitamin A (VA) dietary sources, absorption, and total body VA stores (TBSs) require determination of baseline 13C abundance. 13C-natural abundance is approximately 1.1% total carbon, but varies with foods consumed, supplements taken, and food fortification with synthetic retinyl palmitate. ObjectivesWe determined 13C variation from purified serum retinol and the resulting impact on TBSs using pooled data from preschool children in Burkina Faso, Cameroon, Ethiopia, South Africa, Tanzania, and Zambia and Zambian women. MethodsSeven studies included children (n = 639; 56 ± 25 mo; 48% female) and one in women (n = 138; 29 ± 8.5 y). Serum retinol 13C-natural abundance was determined using GC-C-IRMS. TBSs were available in 7 studies that employed retinol isotope dilution (RID). Serum CRP and α1-acid-glycoprotein (AGP) were available from 6 studies in children. Multivariate mixed models assessed the impact of covariates on retinol 13C. Spearman correlations and Bland–Altman analysis compared serum and milk retinol 13C and evaluated the impact of using study- or global-retinol 13C estimates on calculated TBSs. Results13C-natural abundance (%, median [Q1, Q3]) differed among countries (low: Zambia, 1.0744 [1.0736, 1.0753]; high: South Africa, 1.0773 [1.0769, 1.0779]) and was associated with TBSs, CRP, and AGP in children and with TBSs in women. 13C-enrichment from serum and milk retinol were correlated (r = 0.52; P = 0.0001). RID in children and women using study and global estimates had low mean bias (range, −3.7% to 2.2%), but larger 95% limits of agreement (range, −23% to 37%). Conclusions13C-natural abundance is different among human cohorts in Africa. Collecting this information in subgroups is recommended for surveys using RID. When TBSs are needed on individuals in clinical applications, baseline 13C measures are important and should be measured in all enrolled subjects.

Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein

BackgroundFerritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied. ObjectiveWe aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California. MethodsThis is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP. ResultsAt 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin (r = 0.07 and −0.06; n = 114 at 2 wk; −0.14 and −0.14; n = 95 at 17 wk) or hepcidin (r = 0.18 and −0.03 at 2 wk; −0.05 and −0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02]. ConclusionsLower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states.

Evaluation of In Vitro Distribution and Plasma Protein Binding of Selected Antiviral Drugs (Favipiravir, Molnupiravir and Imatinib) against SARS-CoV-2.

There are a number of uncertainties regarding plasma protein binding and blood distribution of the active drugs favipiravir (FAVI), molnupiravir (MOLNU) and imatinib (IMA), which were recently proposed as therapeutics for the treatment of COVID-19 disease. Therefore, proton dissociation processes, solubility, lipophilicity, and serum protein binding of these three substances were investigated in detail. The drugs display various degrees of lipophilicity at gastric (pH 2.0) and blood pH (pH 7.4). The determined pKa values explain well the changes in lipophilic character of the respective compounds. The serum protein binding was studied by membrane ultrafiltration, frontal analysis capillary electrophoresis, steady-state fluorometry, and fluorescence anisotropy techniques. The studies revealed that the ester bond in MOLNU is hydrolyzed by protein constituents of blood serum. Molnupiravir and its hydrolyzed form do not bind considerably to blood proteins. Likewise, FAVI does not bind to human serum albumin (HSA) and α1-acid glycoprotein (AGP) and shows relatively weak binding to the protein fraction of whole blood serum. Imatinib binds to AGP with high affinity (logK' = 5.8-6.0), while its binding to HSA is much weaker (logK' ≤ 4.0). The computed constants were used to model the distribution of IMA in blood plasma under physiological and 'acute-phase' conditions as well.

Association between Biomarkers of Inflammation and Total Liver Vitamin A Reserves Estimated by 13C-Retinol Isotope Dilution among Preschool Children in 5 African Countries

BackgroundVitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear. ObjectiveWe determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania. MethodsFive studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13C-RID and measurement of inflammation markers, CRP, and α1-acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal–Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]. ResultsComplete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) μmol/g in Ethiopia to 1.10 (0.88, 1.38) μmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = −0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant. ConclusionsNo indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity.

High Procalcitonin, C-Reactive Protein, and α-1 Acid Glycoprotein Levels in Whole Blood Samples Could Help Rapid Discrimination of Active Tuberculosis from Latent Tuberculosis Infection and Healthy Individuals.

Tuberculosis (TB) management is important for prompt discrimination of latent TB infection (LTBI) from active TB and proper treatment. Whole blood Interferon-gamma (IFN-γ) release assay (IGRA) is used to diagnose LTBI based on the secretion of IFN-γ by T-cells in the whole blood by using a specific antigen of Mycobacterium tuberculosis. However, the ability of IGRA to distinguish active TB from LTBI is considerably limited. Distinguishing active TB from LTBI is necessary to identify indicators that can be used to effectively manage TB and develop diagnostic methods. In the present study, we used a Luminex multiplex bead array (a bead-based antibody–antigen sandwich method). The whole blood level of acute phase proteins (APPs), such as endoglin (ENG), procalcitonin (PCT), C-reactive protein (CRP), and α1-acid glycoprotein (AGP), in active TB, LTBI, and healthy individuals were analyzed and quantified. The APP test results for the serum and whole blood samples showed that the levels of PCT, CRP, and AGP were significantly increased (p < 0.0500; area under curve = 0.955) in active TB. The level of these markers in the whole blood of active TB, LTBI, and healthy individuals could provide data for effective diagnosis and treatment of TB.

Association between infection and nutritional status among infants in a cohort study of vitamin A in western Kenya.

BackgroundInfection is associated with impaired nutritional status, especially for infants younger than 5 years.ObjectivesWe assessed the impact of infection indicated by both acute phase proteins (APP), C-reactive protein (CRP), and α-1-acid-glycoprotein (AGP), and as reported by maternal recall on the nutritional status of infants.Materials and methodsA total of 505 pregnant women were enrolled in a nested longitudinal cohort study of vitamin A (VA). Data from 385 children are reported here. The incidence and severity of respiratory infection and diarrhea (previous 14 days) were assessed by maternal recall; infant/child feeding practices were collected. Infant weight, recumbent length, and heel-prick capillary blood were taken at 9 months postpartum. Indicators of the VA status [retinol binding protein (RBP)], iron status (Hb, ferritin), and subclinical inflammation APP, CRP (>5 mg/L), and AGP (>1 g/L) were determined. Impacts of infection on the infant nutritional status were estimated using logistic regression models.ResultsInfection prevalence, based on elevated CRP and AGP levels, was 36.7%. For diarrhea reported symptoms, 42.4% of infants at 9 months had no indication of infection as indicated by CRP and AGP; for acute respiratory reported symptoms, 42.6% had no indication of infection. There was a significant positive association with infection among VA-deficient (RBP < 0.83 μmol/L) infants based on maternal reported symptoms but not with iron deficiency (ferritin < 12 μg/L). The odds of having infection, based on increased CRP and AGP, in underweight infants was 3.7 times higher (OR: 3.7; 95% CI: 2.3, 4.5; P = 0.019). Infants with iron deficiency were less likely (OR: 0.40; 95% CI: 0.1, 0.7; P = 0.001) to have infection based on CRP and AGP, while infants with VA deficiency were five times more likely (OR: 5.06; 95% CI: 3.2, 7.1; P = 0.0001) to have infection.ConclusionAcute phase proteins are more useful in defining infection in a population than reported symptoms of illness. Not controlling for inflammation in a population while assessing the nutritional status might result in inaccurate prevalence estimation.

Associations of bacterial enteropathogens with systemic inflammation, iron deficiency, and anemia in preschool-age children in southern Ghana.

Anemia remains a pervasive public health problem among preschool-age children in Ghana. Recent analyses have found that anemia in Ghanaian children, particularly in Southern regions, is largely attributable to infectious causes, rather than nutritional factors. Infections with enteropathogens can reduce iron absorption and increase systemic inflammation, but few studies have examined direct links between enteropathogens and anemia. This study investigated associations between detection of individual bacterial enteropathogens and systemic inflammation, iron deficiency, and anemia among 6- to 59-month-old children in Greater Accra, Ghana. Serum samples were analyzed from a cross-sectional sample of 262 children for concentrations of hemoglobin (Hb), biomarkers of systemic inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)], and biomarkers of iron status [serum ferritin (SF) and serum transferrin receptor (sTfR)]. Stool samples were analyzed for ten bacterial enteropathogens using qPCR. We estimated associations between presence of each enteropathogen and elevated systemic inflammation (CRP > 5 mg/L and AGP > 1 g/L), iron deficiency (SF < 12 μg/L and sTfR > 8.3 mg/L) and anemia (Hb < 110 g/L). Enteropathogens were detected in 87% of children’s stool despite a low prevalence of diarrhea (6.5%). Almost half (46%) of children had anemia while one-quarter (24%) had iron deficiency (low SF). Despite finding no associations with illness symptoms, Campylobacter jejuni/coli detection was strongly associated with elevated CRP [Odds Ratio (95% CI): 3.49 (1.45, 8.41)] and elevated AGP [4.27 (1.85, 9.84)]. Of the pathogens examined, only enteroinvasive Escherichia coli/Shigella spp. (EIEC/Shigella) was associated with iron deficiency, and enteroaggregative Escherichia coli (EAEC) [1.69 (1.01, 2.84)] and EIEC/Shigella [2.34 (1.15, 4.76)] were associated with anemia. These results suggest that certain enteroinvasive pathogenic bacteria may contribute to child anemia. Reducing exposure to enteropathogens through improved water, sanitation, and hygiene practices may help reduce the burden of anemia in young Ghanaian children.

Biomarkers of Environmental Enteric Dysfunction in Pregnancy and Adverse Birth Outcomes: An Observational Study Among Women Living With HIV in Tanzania

ObjectivesEnvironmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, may contribute to poor fetal growth in low-resource settings. Pregnant women living with HIV may be particularly susceptible to effects of EED, given their increased risk of infections and adverse birth outcomes. We sought to explore the associations of biomarkers of EED, inflammation and growth hormones with birth outcomes in pregnant women living with HIV in Dar es Salaam, Tanzania.MethodsWe performed a sub-study of 706 HIV-infected pregnant women participating in a randomized, double-blind, placebo-controlled trial assessing the effect of vitamin D3 supplementation. Maternal serum samples collected at 32 weeks gestation were analyzed for anti-flagellin and anti-LPS IgA and IgG via ELISA as well as using an 11-plex Micronutrient and EED Assessment Tool, which includes markers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14], systemic inflammation [C-reactive protein and α1-acid glycoprotein (AGP)], insulin-like growth factor 1 (IGF-1) and fibroblast growth factor 21 (FGF21). Biomarkers were categorized as quartiles. Associations with birth outcomes were assessed using linear regression analyses.ResultsPregnant women in the highest quartile of I-FABP had more than twice the risk of stillbirth compared to those in the lowest quartile (RR 2.43, 95% CI 0.98–6.03, ptrend = 0.02). Compared to women in the lowest quartile of AGP, those in the highest quartile gave birth to infants weighing 176g less (95% CI -280 to -71g, ptrend = 0.005). Maternal AGP was associated with increased risk of small-for-gestational age births; those in the highest quartile had a 70% greater risk compared to the lowest (RR 1.70, 95% CI 1.08–2.69, ptrend = 0.03). IGF1 was positively associated with birthweight and birthweight-for-age z-score; FGF21 was negatively associated with gestation duration and risk of preterm birth.ConclusionsMaternal biomarkers of EED, systemic inflammation, and the growth hormone axis were associated with birth outcomes. Further studies are needed to confirm these results and study the biologic mechanisms involved.Funding SourcesNational Institutes of Health (NICHD, NIDDK).