Temporal changes in N‐acylethanolamine content and metabolism throughout the peri‐adolescent period

Fatty acid amide hydrolase (FAAH) regulates tissue concentrations of N‐acylethanolamines (NAEs), including the endocannabinoid, N‐arachidonylethanolamide (anandamide, AEA). FAAH activity and NAEs are widely distributed throughout the brain and FAAH activity regulates an array of processes including emotion, cognition, inflammation, and feeding. However, there is relatively little research describing how this system develops throughout adolescence, particularly within limbic circuits regulating stress and reward processing. Thus, this study characterized temporal changes in NAE content (AEA, oleoylethanolamine [OEA], and palmitoylethanolamide [PEA]) and FAAH activity across the peri‐adolescent period, in four corticolimbic structures (amygdala, hippocampus, prefrontal cortex, and hypothalamus). Brain tissue of male Sprague–Dawley rats was collected on postnatal days (PND) 25, 35, 45, and 70, representing pre‐adolescence, early‐ to mid‐adolescence, late adolescence, and adulthood, respectively. Tissue was analyzed for AEA, OEA, and PEA content as well as FAAH activity at each time point. AEA, OEA, and PEA exhibited a similar temporal pattern in all four brain regions. NAE concentrations were lowest at PND 25 and highest at PND 35. NAE concentrations decreased between PNDs 35 and 45 and increased between PNDs 45 and 70. FAAH activity mirrored the pattern of NAE content in which it decreased between PNDs 25 and 35, increased between PNDs 35 and 45, and decreased between PNDs 45 and 70. These age‐dependent patterns of NAE content and FAAH activity demonstrate temporal specificity to the development of this system and could contribute to alterations in stress sensitivity, emotionality, and executive function which also fluctuate during this developmental period. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

Fatal Taxus baccata ingestion with perimortem serum taxine B quantification

Introduction: Common yew (Taxus baccata) is a common decorative evergreen shrub with potentially fatal toxicity hallmarked by seizure, arrhythmia and cardiovascular collapse if ingested. Taxine B has been identified as one of the most cardiotoxic taxine alkaloids in Taxus spp, and another alkaloid, 3,5-dimethoxyphenol (3,5-DMP), is used as a marker of ingestion. We present a fatal case of ingestion of yew with perimortem serum and gastric taxine B, and 3,5-DMP concentrations.

Case presentation: A 22-year-old woman was brought to the emergency department (ED) from a nearby botanical garden after she was found apneic and pulseless after a witnessed generalized tonic clonic seizure. The patient was found to have a wide complex rhythm with persistent cardiovascular collapse and expired despite maximal supportive care in the ED. A baggie of plant material was found on the patient, identified as Taxus baccata. Perimortem serum and gastric samples were analyzed to quantify serum and gastric taxine B and 3,5-DMP concentrations.

Results: Perimortem serum showed a 3,5-DMP concentration of 86.9 ng/mL, and taxine B of 80.9 ug/mL.

Conclusion: We report a perimortem serum and gastric taxine B and 3,5-DMP concentrations in a fatal case of T. baccata toxicity.     

Enrichment improves cognition in AD mice by amyloid-related and unrelated mechanisms

Lifelong cognitive stimulation is associated with a lower risk of Alzheimer's disease (AD), but causality is difficult to prove. We therefore sought to investigate the preventative potential of environmental enrichment (EE) using mice expressing both human mutant presenilin-1 and the amyloid precursor protein (PS1/PDAPP). At weaning, mice were placed into either an enriched or standard housing environment. Behavioral testing at 4.5-6 months showed that environmentally enriched PS1/PDAPP mice outperformed mice in standard housing, and were behaviorally indistinguishable from non-transgenic mice across multiple cognitive domains. PS1/PDAPP mice exposed to both environmental enrichment and behavioral testing, but not to EE alone, showed 50% less brain beta-amyloid without improved dendritic morphology. Microarray analysis revealed large enrichment-induced changes in hippocampal expression of genes/proteins related to Abeta sequestration and synaptic plasticity. These results indicate that EE protects against cognitive impairment in AD transgenic mice through a dual mechanism, including both amyloid dependent and independent mechanisms.     

Genetic variations of HLA-DRB1 and susceptibility to Kawasaki disease in Taiwanese children

Although some previous studies have reported that genetic and immunologic factors play important roles in the pathogenesis of Kawasaki disease (KD), the etiologic factors of this enigmatic pediatric disease are still poorly understood. The purpose of this study was to investigate whether polymorphisms of the human leukocyte antigen DRB1 (HLA-DRB1) gene are associated with KD and the development of coronary artery lesions (CAL) in Taiwanese children. Genomic DNA was extracted from whole blood samples from 145 children with KD and 331 healthy controls. The HLA-DRB1 gene was genotyped by polymerase chain reaction (PCR) and sequence-based typing assays. We found that the distribution of HLA-DRB1 allele families and alleles in children with KD did not differ from that in healthy controls. Stratified analysis did not demonstrate any association between particular HLA-DRB1 allele families or alleles and the development of CAL in children with KD. These findings suggest that susceptibility to KD and CAL is not associated with the HLA-DRB1 gene in a Taiwanese population. If immunogenetic determinants are involved in this disease and its complications in Taiwanese children, they must involve genes other than HLA-DRB1.     

Alteration of renal excretion pathways in gentamicin‐induced renal injury in rats

The kidney plays a major part in the elimination of many drugs and their metabolites, and drug‐induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)‐induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg^–1), and creatinine concentration was increased by 39.7% by GEN (50 mg kg^–1). GEN dose‐dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p‐aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs‐rMATE1 and rOAT3‐rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)‐induced acute kidney injury caused the downregulated function of glomerular filtration ‐rOCTs‐rMATE1 and ‐rOAT1‐rMRPs pathway.     

Feasibility and Acceptability of Delivering a Postpartum Weight Loss Intervention via Facebook: A Pilot Study

Objective

To evaluate the feasibility and acceptability of a Facebook-delivered postpartum weight loss intervention.