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- Benterud, T, et al.
(författare)
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Cerebellum Susceptibility to Neonatal Asphyxia: Possible Protective Effects of N-Acetylcysteine Amide
- 2018
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Ingår i: Disease markers. - : Hindawi Limited. - 1875-8630 .- 0278-0240. ; 2018, s. 5046372-
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Tidskriftsartikel (refereegranskat)abstract
- Background. After perinatal asphyxia, the cerebellum presents more damage than previously suggested. Objectives. To explore if the antioxidant N-acetylcysteine amide (NACA) could reduce cerebellar injury after hypoxia-reoxygenation in a neonatal pig model. Methods. Twenty-four newborn pigs in two intervention groups were exposed to 8% oxygen and hypercapnia, until base excess fell to −20 mmol/l or the mean arterial blood pressure declined to <20 mmHg. After hypoxia, they received either NACA (NACA group, n=12) or saline (vehicle-treated group, n=12). One sham-operated group (n=5) served as a control and was not subjected to hypoxia. Observation time after the end of hypoxia was 9.5 hours. Results. The intranuclear proteolytic activity in Purkinje cells of asphyxiated vehicle-treated pigs was significantly higher than that in sham controls (p=0.03). Treatment with NACA was associated with a trend to decreased intranuclear proteolytic activity (p=0.08), There were significantly less mutations in the mtDNA of the NACA group compared with the vehicle-treated group, 2.0 × 10−4 (±2.0 × 10−4) versus 4.8 × 10−5(±3.6 × 10−4, p<0.05). Conclusion. We found a trend to lower proteolytic activity in the core of Purkinje cells and significantly reduced mutation rate of mtDNA in the NACA group, which may indicate a positive effect of NACA after neonatal hypoxia. Measuring the proteolytic activity in the nucleus of Purkinje cells could be used to assess the effect of different neuroprotective substances after perinatal asphyxia.
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- Benterud, T, et al.
(författare)
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N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
- 2017
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Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 111:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. <b><i>Objectives:</i></b> To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs. <b><i>Methods:</i></b> Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. <b><i>Results:</i></b> Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65<sup>Ser 536</sup>), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01). <b><i>Conclusion:</i></b> The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
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- Kro, GA, et al.
(författare)
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Association between umbilical cord artery pCO₂ and the Apgar score; elevated levels of pCO₂ may be beneficial for neonatal vitality after moderate acidemia.
- 2013
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons Ltd.. - 0001-6349 .- 1600-0412. ; 92:6, s. 662-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the association between 5-min Apgar score and umbilical cord artery carbon dioxide tension (pCO₂). DESIGN: Observational study. SETTING: European hospital labor wards. POPULATION: Data from 36,432 newborns ≥36 gestational weeks were obtained from three sources: two trials of monitoring with fetal electrocardiogram (the Swedish randomized controlled trial and the European Union Fetal ECG trial) and Mölndal Hospital data. After validation of the acid-base values, 25,806 5-min Apgar scores were available for analysis. METHODS: Validation of the umbilical cord acid-base values was performed to obtain reliable data. 5-min Apgar score was regressed against cord artery pCO₂ in a polynomial multilevel model. MAIN OUTCOME MEASURES: Five-min Apgar score, umbilical cord pCO₂, pH, and base deficit. RESULTS: Overall, a higher cord artery pCO₂ was found to be associated with lower 5-min Apgar scores. However, among newborns with moderate acidemia, lower umbilical cord artery pCO₂ (≤median pCO₂ for the specific cord artery pH) was associated with lower 5-min Apgar scores, with a relative risk of 2.0 (95% confidence interval: 1.4-2.8) for 5-min Apgar scores 0-6. CONCLUSIONS: Metabolic acidosis affects the newborn's vitality more than respiratory acidosis. In addition, elevated levels of pCO₂ may be beneficial for fetuses with moderate acidemia, and thus cord artery pCO₂ is a factor that should be considered when assessing the compromised newborn.
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