Splanchnic oxygen saturation during reoxygenation with 21% or 100% O-2 in newborn piglets

Background Increasing evidence recognizes the harm of excess oxygen to lungs, eyes, and brain of preterm infants, but not yet to the intestine. We assessed changes in splanchnic oxygenation during reoxygenation with 21% compared to 100% O-2 in a newborn piglet model of perinatal asphyxia. Methods We randomized 25 piglets to control or intervention. Intervention groups underwent global hypoxia until acidosis and hypotension occurred. Piglets were reoxygenated for 30 min with 21% or 100% O-2 and observed for 9 h. We continuously measured regional splanchnic oxygen saturation (r(s)SO(2)) using near-infrared spectroscopy (NIRS). We calculated mean r(s)SO(2) and r(s)CoVar (as SD/mean). We measured PaO2 and SaO(2), sampled from the right carotid artery.  Results Reoxygenation after global hypoxia restored r(s)SO(2). Reoxygenation with 100% O-2 increased r(s)SO(2) to values significantly higher than baseline. In intervention groups, r(s)CoVar decreased during observation compared to baseline. We found a correlation between r(s)SO(2) and PaO2 (r = 0.420, P < 0.001) and between r(s)SO(2) and SaO(2) (r = 0.648, P < 0.001) in pooled data from the entire experiment. Conclusion Reoxygenation after global hypoxia improves splanchnic oxygenation, but is associated with reduced variability of r(s)SO(2). Reoxygenation with 100% O-2 exposes the intestine to hyperoxia. Splanchnic NIRS is able to detect intestinal hypoxia and hyperoxia. Impact Splanchnic oxygenation improves during reoxygenation after global hypoxia, though reoxygenation with 100% O2 exposes the intestine to hyperoxia. Decreased variability of splanchnic oxygenation several hours after hypoxia and reoxygenation seems to be independent of the resuscitation strategy, and may indicate intestinal injury. Splanchnic NIRS monitoring was able to detect intestinal hypoxia and exposure to hyperoxia, as evidenced by a strong correlation between splanchnic oxygenation and arterial oxygen content

Ochratoxin A: a naturally occurring mycotoxin found in human milk samples from Norway

Fagfellevurdert artikkel publisert i tidsskriftet Acta Paediatrica. Versjonen som er lagt ut her, er forfatterens pre-printversjon.The presence of ochratoxin A (OA) in human milk samples from different regions in Norway has been investigated in order to determine the level of infant exposure to OA from human milk. OA was found in 38 (33%) of 115 human milk samples (range 10-130 ng/l). Two to 26 % of the samples contained more than 40 ng/l OA, which will cause a daily intake of OA from human milk exceeding the suggested tolerable dose of 5 ng/kg bw. Significant regional differences were found

Presence of ochratoxin A in human milk in relation to dietary intake

Dette er forfatterens pre-printversjon av artikkelen. Den publiserte versjonen kan leses her: http://web.ebscohost.com/ehost/detail?sid=9c936566-3535-4668-a544-9b2202c25ac8%40sessionmgr198&vid=1&hid=112&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=aph&AN=4425106Individual and geographical variations in ochratoxin A (OA) levels in human blood and milk samples may be due to differences in dietary habits. The purpose of this study was to examine the relationship between OA contamination of human milk and dietary intake. Human milk samples were collected from 80 Norwegian women. The usual food intake during the last year was recorded using a quantitative food frequency questionnaire. The concentration of OA in the human milk was determined by HPLC (detection limit 10 ng/l). Seventeen (21%) out of 80 human milk samples contained OA in the range 10 - 182 ng/l. The women with a high dietary intake of liver paste (liverwurst, liver pâté) and cakes (cookies, fruitcakes, chocolate cakes etc.) were more likely to have OA-contaminated milk. The risk of OA contamination was also increased by the intake of juice (all kinds). In addition, the results indicate that breakfast cereals, processed meat products, and cheese could be important contributors to dietary OA intake. OA contamination of the milk was unrelated to smoking, age, parity, and anthropometric data other than body weight

Long Non-Coding RNAs in Hypoxia and Oxidative Stress:Novel Insights Investigating a Piglet Model of Perinatal Asphyxia

Birth asphyxia is the leading cause of death and disability in young children worldwide. Long non-coding RNAs (lncRNAs) may provide novel targets and intervention strategies due to their regulatory potential, as demonstrated in various diseases and conditions. We investigated cardinal lncRNAs involved in oxidative stress, hypoxia, apoptosis, and DNA damage using a piglet model of perinatal asphyxia. A total of 42 newborn piglets were randomized into 4 study arms: (1) hypoxia–normoxic reoxygenation, (2) hypoxia–3 min of hyperoxic reoxygenation, (3) hypoxia–30 min of hyperoxic reoxygenation, and (4) sham-operated controls. The expression of lncRNAs BDNF-AS, H19, MALAT1, ANRIL, TUG1, and PANDA, together with the related target genes VEGFA, BDNF, TP53, HIF1α, and TNFα, was assessed in the cortex, the hippocampus, the white matter, and the cerebellum using qPCR and Droplet Digital PCR. Exposure to hypoxia–reoxygenation significantly altered the transcription levels of BDNF-AS, H19, MALAT1, and ANRIL. BDNF-AS levels were significantly enhanced after both hypoxia and subsequent hyperoxic reoxygenation, 8% and 100% O2, respectively. Our observations suggest an emerging role for lncRNAs as part of the molecular response to hypoxia-induced damages during perinatal asphyxia. A better understanding of the regulatory properties of BDNF-AS and other lncRNAs may reveal novel targets and intervention strategies in the future.</p

Metabolomic Analyses of Plasma Reveals New Insights into Asphyxia and Resuscitation in Pigs

Currently, a limited range of biochemical tests for hypoxia are in clinical use. Early diagnostic and functional biomarkers that mirror cellular metabolism and recovery during resuscitation are lacking. We hypothesized that the quantification of metabolites after hypoxia and resuscitation would enable the detection of markers of hypoxia as well as markers enabling the monitoring and evaluation of resuscitation strategies.Hypoxemia of different durations was induced in newborn piglets before randomization for resuscitation with 21% or 100% oxygen for 15 min or prolonged hyperoxia. Metabolites were measured in plasma taken before and after hypoxia as well as after resuscitation. Lactate, pH and base deficit did not correlate with the duration of hypoxia. In contrast to these, we detected the ratios of alanine to branched chained amino acids (Ala/BCAA; R(2).adj = 0.58, q-value<0.001) and of glycine to BCAA (Gly/BCAA; R(2).adj = 0.45, q-value<0.005), which were highly correlated with the duration of hypoxia. Combinations of metabolites and ratios increased the correlation to R(2)adjust = 0.92. Reoxygenation with 100% oxygen delayed cellular metabolic recovery. Reoxygenation with different concentrations of oxygen reduced lactate levels to a similar extent. In contrast, metabolites of the Krebs cycle (which is directly linked to mitochondrial function) including alpha keto-glutarate, succinate and fumarate were significantly reduced at different rates depending on the resuscitation, showing a delay in recovery in the 100% reoxygenation groups. Additional metabolites showing different responses to reoxygenation include oxysterols and acylcarnitines (n = 8-11, q<0.001).This study provides a novel strategy and set of biomarkers. It provides biochemical in vivo data that resuscitation with 100% oxygen delays cellular recovery. In addition, the oxysterol increase raises concerns about the safety of 100% O(2) resuscitation. Our biomarkers can be used in a broad clinical setting for evaluation or the prediction of damage in conditions associated with low tissue oxygenation in both infancy and adulthood. These findings have to be validated in human trials

No replication of previously reported association with genetic variants in the T cell receptor alpha (TRA) locus for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/.Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease with a variety of symptoms such as post-exertional malaise, fatigue, and pain, but where aetiology and pathogenesis are unknown. An increasing number of studies have implicated the involvement of the immune system in ME/CFS. Furthermore, a hereditary component is suggested by the reported increased risk for disease in relatives, and genetic association studies are being performed to identify potential risk variants. We recently reported an association with the immunologically important human leucocyte antigen (HLA) genes HLA-C and HLA-DQB1 in ME/ CFS. Furthermore, a genome-wide genetic association study in 42 ME/CFS patients reported significant association signals with two variants in the T cell receptor alpha (TRA) locus (P value.publishedVersio

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

The etiology and pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown, and autoimmunity is one of many proposed underlying mechanisms. Human Leukocyte Antigen (HLA) associations are hallmarks of autoimmune disease, and have not been thoroughly investigated in a large ME/CFS patient cohort. We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. Clinical information was collected through questionnaires completed by patients or relatives. We discovered two independent HLA associations, tagged by the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4–3.1]) and HLA-DQB1*03:03 (OR 1.5 [95% CI 1.1–2.0]). These alleles were carried by 7.7% and 12.7% of ME/CFS patients, respectively. The proportion of individuals carrying one or both of these alleles was 19.2% in the patient group and 12.2% in the control group (OR 1.7 [95% CI 1.3–2.2], pnc = 0.00003). ME/CFS is a complex disease, potentially with a substantial heterogeneity. We report novel HLA associations pointing toward the involvement of the immune system in ME/CFS pathogenesis.publishedVersio

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

Background: In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods: Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results: Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions: BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD

Comparison of whole genome expression profile between preterm and full-term newborns

Objectives: Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression after birth. Material and methods: The study was carried out on 20 full-term newborns and 62 preterm newborns (mean birth weight = 1002 [g] (SD: 247), mean gestational age = 27.2 weeks (SD: 1.9)). Blood samples were drawn from all the study participants at birth and at the 36th week postmenstrual age from the preterm group to assess whole genome expression in umbilical cord blood and in peripheral blood leukocytes, respectively. (SurePrint G3 Human Gene Expression v3, 8x60K Microarrays (Agilent)). Results: A substantial number of genes was found to be expressed differentially at the time of birth and at 36 PMA in comparison to the term babies with more genes being down-regulated than up-regulated. However, the fold change in the majority of cases was &lt; 2.0. Extremely preterm and very preterm infants were characterized by significantly down-regulated cytokine and chemokine related pathways. The number of down-regulated genes decreased and number of up-regulated genes increased at 36 PMA vs. cord blood. There were no specific gene expression pathway profiles found within the groups of different gestational ages. Conclusions: Preterm delivery is associated with a different gene expression profile in comparison to term delivery. The gene expression profile changes with the maturity of a newborn measured by the gestational age