Hypoxia in human NT2-N neurons : The role of acidosis, mitochondria and inflammation

Approximately 4 million infants out of 130 million worldwide annual births suffer from birth asphyxia. Of these, approximately 25% die and 25% develop some kind of neurological sequelae (UNICEF 2003). In the western part of the world, 2-6/1000 of all newborn are diagnosed with HIE, hypoxic ischemic encephalopathy, during the first days of life, due to reduced gas exchange through placenta or lungs. The overall aim for this thesis in pediatric neurology was to understand more about the mechanisms behind hypoxic-ischemic brain damage, so that treatment for this important condition hopefully can be improved. We focused our research on acidosis, mitochondrial function and inflammation, all important but not fully understood phenomena in hypoxic-ischemic brain damage and all possibly amendable to interventional treatment. Hypoxia studies were done in NT2-N neurons, a human cell line consisting of postmitotic, differentiated fenotypic neurons. Analyses were done for cell death, energy level, mitochondrial function and different mediators of inflammation. Acidosis was confirmed to have a protective effect during hypoxia and a detrimental effect early during reoxygenation. Further, an early decline in mitochondrial function was found. Inflammation played a role during hypoxic-ischemic brain damage. Finally, the results showed neuronal damage to occur several hours after the insult. This “delayed” cell death gives the possibility of beneficial intervention during this “therapeutic time window”

Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and promotes weight gain in mice fed a low fat diet

Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA–PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet

Assessment of infant formulae based on partially hydrolysed proteins Norwegian. Opinion of the Panel on nutrition, dietetics products, novel food and allergy of the Norwegian Scientific Committee for Food Safety

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Assessment of infant formulae based on partially hydrolysed proteins Norwegian. Opinion of the Panel on nutrition, dietetics products, novel food and allergy of the Norwegian Scientific Committee for Food Safety

The regulation of infant formulas is under revision, including the national restriction on sales of infant formulas with partially hydrolysed proteins to pharmacies only. In December 2007 the Norwegian Food Safety Authority requested an opinion from the Norwegian Scientific Committee for Food Safety on infant formulas with partially hydrolysed protein. The opinion should cover an evaluation of risks associated with the replacement of conventional infant formulae (based on intact protein) by infant formula based on partially hydrolysed protein, including a specification of the risks associated with the consumption of infant formula based on partially hydrolysed proteins among infants with cow’s milk allergy. Furthermore, the opinion should include an evaluation of the preventive effect from formula with partially hydrolysed proteins on development of cow’s milk allergy. To complete this task, VKM has established an ad hoc group that has prepared this report. The Panel on Nutrition, Dietetic Products, Novel Food and Allergy has discussed and adopted this opinion. The main conclusions are that although no studies show that partially hydrolysed formulas have negative effect on growth, measures should be taken in order to avoid that partially hydrolysed formulas replace regular infant formulas in the general population. Hydrolysed proteins have a high absorption rate, and ingestion of hydrolysed proteins have been shown to increase gastric emptying and plasma glucose-dependent insulinotropic polypeptide relative to the intact protein forms. Feeding partially hydrolysed formulas to infants with cow’s milk allergy constitutes a risk of eliciting an allergic reaction which in worst case may be fatal. The risk that an infant with cow’s milk allergy will receive partially hydrolysed formula may increase if the products are sold with claims such as reduced risk towards cow’s milk allergy and reduced risk of developing cow’s milk allergy together with ordinary infant formula outsides pharmacies. The risk of developing cow’s milk allergy is not shown to be reduced by introducing partially hydrolysed formula instead of regular formula during the first 4-6 months. There has not been demonstrated any preventive effect from hydrolysed formulas after the age of 6 months on the development of allergic disease.publishedVersio