Influence of Maternal Age and Gestational Age on Breast Milk Antioxidants During the First Month of Lactation.

Breast milk (BM) is beneficial due to its content in a wide range of different antioxidants, particularly relevant for preterm infants, who are at higher risk of oxidative stress. We hypothesize that BM antioxidants are adapted to gestational age and are negatively influenced by maternal age. Fifty breastfeeding women from two hospitals (Madrid, Spain) provided BM samples at days 7, 14 and 28 of lactation to assess total antioxidant capacity (ABTS), thiol groups, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activities, lipid peroxidation (malondialdehyde, MDA + 4-Hydroxy-Trans-2-Nonenal, HNE), protein oxidation (carbonyl groups) (spectrophotometry) and melatonin (ELISA). Mixed random-effects linear regression models were used to study the influence of maternal and gestational ages on BM antioxidants, adjusted by days of lactation. Regression models evidenced a negative association between maternal age and BM melatonin levels (ß = -7.4 ± 2.5; p-value = 0.005); and a negative association between gestational age and BM total antioxidant capacity (ß = -0.008 ± 0.003; p-value = 0.006), SOD activity (ß = -0.002 ± 0.001; p-value = 0.043) and protein oxidation (ß = -0.22 ± 0.07; p-value = 0.001). In conclusion, BM antioxidants are adapted to gestational age providing higher levels to infants with lower degree of maturation; maternal ageing has a negative influence on melatonin, a key antioxidant hormone.

Parainfluenza 3 Respiratory Infection Associated with Pericardial Effusion in a Very Low Birthweight Infant.

Parainfluenza 3 virus is a frequent cause of respiratory infections in the pediatric population although it is uncommonly diagnosed in neonates, being usually reported as neonatal intensive care unit microepidemics. We report a case of parainfluenza 3 respiratory infection associated with pericardial effusion in a very low birthweight infant.

ß-Amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-α, PPAR-γ and TRPV1, but not CB1 or CB2 receptors.

BACKGROUND AND PURPOSE: The endocannabinoid system may regulate glial cell functions and their responses to pathological stimuli, specifically, Alzheimer's disease. One experimental approach is the enhancement of endocannabinoid tone by blocking the activity of degradative enzymes, such as fatty acid amide hydrolase (FAAH). EXPERIMENTAL APPROACH: We examined the role of FAAH in the response of astrocytes to the pathologic form of ß-amyloid (Aß). Astrocytes from wild-type mice (WT) and from mice lacking FAAH (FAAH-KO) were incubated with Aß for 8, 24 and 48 h, and their inflammatory responses were quantified by elisa, western-blotting and real-time quantitative-PCR. KEY RESULTS: FAAH-KO astrocytes were significantly more responsive to Aß than WT astrocytes, as shown by the higher production of pro-inflammatory cytokines. Expression of COX-2, inducible NOS and TNF-α was also increased in Aß-exposed KO astrocytes compared with that in WTs. These effects were accompanied by a differential pattern of activation of signalling cascades involved in mediating inflammatory responses, such as ERK1/2, p38MAPK and NFκB. PPAR-α and PPAR-γ as well as transient receptor potential vanilloid-1 (TRPV1), but not cannabinoid CB1 or CB2 receptors, mediate some of the differential changes observed in Aß-exposed FAAH-KO astrocytes. The pharmacological blockade of FAAH did not render astrocytes more sensitive to Aß. In contrast, exogenous addition of several acylethanolamides (anandamide, palmitoylethanolamide and oleoylethanolamide) induced an antiinflammatory response. CONCLUSIONS: The genetic deletion of FAAH in astrocytes exacerbated their inflammatory phenotype against Aß in a process involving PPAR-α, PPAR-γ and TRPV1 receptors.

The endocannabinoid system and amyloid-related diseases.

The endocannabinoid system may be the target of novel therapies in a wide variety of diseases. Among them, those related with amyloid accumulation will be discussed in the present review. Several components of this system (CB1 and CB2 receptors, endocannabinoids, FAAH enzyme) may participate in different aspects of amyloid pathophysiology such as, for instance, synaptic activity, cell migration, cytokine production or phagocytic activity. Consistent with recent data, putative lines of research and hypothesis will be discussed.

The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages.

The endocannabinoid system is a promising therapeutic target in a wide variety of diseases. However, the non-desirable psychotropic effects of natural and synthetic cannabinoids have largely counteracted their clinical usefulness. These effects are mostly mediated by cannabinoid receptors of the CB(1) type, that exhibit a wide distribution in neuronal elements of the CNS. Thus, the presence of other elements of this system in the CNS, such as CB(2) receptors, may open new possibilities for the development of cannabinoid-based therapies. These receptors are almost absent from the CNS in normal conditions but are up-regulated in glial cells under chronic neuroinflammatory stimuli, as has been described in Alzheimer's disease. To understand the functional role of these receptors, we tested their role in the process of beta-amyloid removal, that is currently considered as one of the most promising experimental approaches for the treatment of this disease. Our results show that a CB(2) agonist (JWH-015) is capable of inducing the removal of native beta-amyloid removal from human frozen tissue sections as well as of synthetic pathogenic peptide by a human macrophage cell line (THP-1). Remarkably, this effect was achieved at low doses (maximum effect at 10 nM) and was specific for this type of cells, as U373MG astrocytoma cells did not respond to the treatment. The effect was CB(2)-mediated, at least partially, as the selective CB(2) antagonist SR144528 prevented the JWH-015-induced plaque removal in situ. These data corroborate the possible therapeutic interest of CB(2) cannabinoid specific chemicals in the treatment of Alzheimer's disease.