Palmitoylethanolamide Exerts Antiproliferative Effect and Downregulates VEGF Signaling in Caco‐2 Human Colon Carcinoma Cell Line Through a Selective PPAR‐α‐Dependent Inhibition of Akt/mTOR Pathway

Palmitoylethanolamide (PEA) is a nutraceutical compound that has been demonstrated to improve intestinal inflammation. We aimed at evaluating its antiproliferative and antiangiogenic effects in human colon adenocarcinoma Caco‐2 cell line. Caco‐2 cells were treated with increasing concentrations of PEA (0.001, 0.01 and 0.1 μM) in the presence of peroxisome proliferator‐activated receptor‐a (PPAR‐α) or PPAR‐γ antagonists. Cell proliferation was evaluated by performing a MTT assay. Vascular endothelial growth factor (VEGF) release was estimated by ELISA, while the expression of VEGF receptor and the activation of the Akt/mammalian target of rapamycin (mTOR) pathway were evaluated by western blot analysis. PEA caused a significant and concentration‐dependent decrease of Caco‐2 cell proliferation at 48 h. PEA administration significantly reduced in a concentration‐dependent manner VEGF secretion and VEGF receptor expression. Inhibition of Akt phosphorylation and a downstream decrease of phospho‐mTOR and of p‐p70S6K were observed as compared with untreated cells. PPAR‐α, but not PPAR‐γ antagonist, reverted all effects of PEA. PEA is able to decrease cell proliferation and angiogenesis. The antiangiogenic effect of PEA depends on the specific inhibition of the AkT/mTOR axis, through the activation of PPAR‐α pathway. If supported by in vivo models, our data pave the way to PEA co‐administration to the current chemotherapeutic regimens for colon carcinoma. Copyright © 2016 John Wiley & Sons, Ltd.     

Evaluation of body composition in neonates and infants

A better understanding of the nutritional needs of both healthy and sick infants is important. Not only does too much or too little nutrition during early life have long-term effects on health, but periods of rapid growth during the first year of life also have long-term consequences. Knowledge of the changes in body composition in early life can help to better define nutritional needs at these ages. Several methods are available for measuring body composition of neonates and infants. Most focus on an assessment of either body fatness or bone mineralization; only a few can monitor the quality of the non-fat lean tissues. This paper provides an evaluation of the different approaches currently available to monitor infant body composition, identifying both their strengths and limitations.     

2型糖尿病家系人群两种基因多态性分布

目的检测中国常州汉族2型糖尿病家系人群中PEA 15基因与KCNJ 10基因中2个单核苷酸位点多态性分布情况,探讨该遗传标记与2型糖尿病的关系。方法采用聚合酶链反应-限制性酶切片段长度多态性（PCR-RFLP）方法对该地区55个2型糖尿病高发家系265名成员的PEA 15基因（rs8175359）及KCNJ 10基因（rs2486253）2个单核苷酸多态性位点（SNPs）进行分析。结果在2型糖尿家系人群中,rs8175359位点基因型频率为：病例组中GG、GA分别为98.6%,1.4%;在未患病亲属组中为GG 99.2%,GA 0.8%,未发现AA纯合子。rs2486253位点基因型频率为：病例组中GG、GT分别为92.9%,7.1%;在未患病亲属组中为GG 91.1%,GT 8.9%。2组间基因型频率、等位基因频率的差异均无统计学意义。按性别等因素分层分析显示,rs2486253位点基因型频率构成比差异均无统计学意义。结论该两位点是否可作为2型糖尿的相关遗传标记需进一步在大样本人群研究中重复验证。     

Fatty Acid-Derived N-acylethanolamines Dietary Supplementation Attenuates Neuroinflammation and Cognitive Impairment in LPS Murine Model

Neuroinflammation plays a critical role in the pathogenesis of most neurological and neurodegenerative diseases and therefore represents a potential therapeutic target. In this regard, accelerating the resolution process in chronic neuroinflammation may be an effective strategy to deal with the cognitive consequences of neuropathology and generalized inflammatory processes. N-acylethanolamine (NAE) derivatives of fatty acids, being highly active lipid mediators, possess pro-resolving activity in inflammatory processes and are promising agents for the suppression of neuroinflammation and its consequences. This paper is devoted to a study of the effects played by dietary supplement (DS), containing a composition of fatty acid-derived NAEs, obtained from squid Berryteuthis magister, on the hippocampal neuroinflammatory and memory processes. By detecting the production of pro-inflammatory cytokines and glial markers, a pronounced anti-inflammatory activity of DS was demonstrated both in vitro and in vivo. DS administration reversed the LPS-induced reduction in hippocampal neurogenesis and memory deterioration. LC-MS analysis revealed an increase in the production of a range of NAEs with well-documented anti-inflammatory activity in response to the administered lipid composition. To conclude, we found that tested DS suppresses the neuroinflammatory response by reducing glial activation, positively regulates neural progenitor proliferation, and attenuates hippocampal-dependent memory impairment.     

玻璃体切割联合前部超声乳化及IOL植入的评估

目的观察评估玻璃体切割手术的同时联合进行超声乳化白内障囊外摘除和IOL植入治疗并发晶状体混浊的玻璃体积血的术后效果。方法回顾性分析我院2003/2004期间28例并发有晶状体混浊的玻璃体积血患者,分别进行保留晶状体和联合前部超声乳化的玻璃体切除手术。结果联合手术在手术操作,术后反应与保留晶状体眼无明显差别,术后视功能恢复上要优于保留晶状体眼。结论对并发晶状体混浊的玻璃体积血患者玻璃体切割手术的同时联合进行超声乳化白内障囊外摘除和IOL植入治疗的术后效果显著。     

Neuroprotective effects of dynamic bubble trap use in patients undergoing pulmonary endarterectomy: a two-arm randomized controlled trial

BackgroundDuring cardiosurgical procedures that use extracorporeal circulation (ECC), a variety of neurological complications can occur, and postoperative cognitive deficits remain an unsolved problem. Among the sources of these complications are intraoperatively detectable cerebral microemboli, which mainly consist of air. This study’s purpose was to assess neuroprotective effects of reducing these gaseous microemboli using a dynamic bubble trap (DBT) in patients undergoing pulmonary endarterectomy (PEA) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH).MethodsPatients undergoing PEA were randomly assigned to receive either a DBT (n=47) or no additional device (controls, n=46) during ECC. Neuropsychological testing was performed before and 3 months after PEA. The primary endpoint was cognitive improvement in the DBT group (n=29) compared with the control group (n=42). As secondary endpoint, ischemic brain micro-lesions were analyzed on postoperative days 6 through 10 using diffusion-weighted magnetic resonance imaging (MRI).ResultsAnalysis of interaction effects revealed improved performance in visual long-term memory (P=0.008, η²=0.099), verbal long-term memory (P=0.030, η²=0.067), verbal short-term memory (P=0.014, η²=0.083), and attention and processing speed (P=0.043, η²=0.056) from pre- to post-testing in the DBT group compared to control group. In MRI, postoperative ischemic micro-lesions could only be detected in one patient; another patient suffered a severe bihemispheric embolic stroke.ConclusionsDBT positively influences memory function after PEA. This effect is most likely caused by the reduction of gaseous microemboli.Trial RegistrationThis study is registered in the German Clinical Trials Register, ID: DRKS00021499.     

Cannabinoid receptors: nomenclature and pharmacological principles

The CB1 and CB2 cannabinoid receptors are members of the G protein-coupled receptor (GPCR) family that are pharmacologically well defined. However, the discovery of additional sites of action for endocannabinoids as well as synthetic cannabinoid compounds suggests the existence of additional cannabinoid receptors. Here we review this evidence, as well as the current nomenclature for classifying a target as a cannabinoid receptor. Basic pharmacological definitions, principles and experimental conditions are discussed in order to place in context the mechanisms underlying cannabinoid receptor activation. Constitutive (agonist-independent) activity is observed with the overexpression of many GPCRs, including cannabinoid receptors. Allosteric modulators can alter the pharmacological responses of cannabinoid receptors. The complex molecular architecture of each of the cannabinoid receptors allows for a single receptor to recognize multiple classes of compounds and produce an array of distinct downstream effects. Natural polymorphisms and alternative splice variants may also contribute to their pharmacological diversity. As our knowledge of the distinct differences grows, we may be able to target select receptor conformations and their corresponding pharmacological responses. Importantly, the basic biology of the endocannabinoid system will continue to be revealed by ongoing investigations.     

Central odor processing in subjects experiencing helplessness

The aim of the present study was to investigate whether central nervous odor processing is affected by the temporary experience of helplessness. To induce helplessness, an unsolvable social discrimination test in combination with false feedback was used. The EEG was recorded from 60 scalp locations, while two standard odors were presented via a constant-flow olfactometer. Helplessness attenuated olfactory stimulus processing at an early perceptual stage: the P2 and P3-1 amplitudes were reduced in response to both odors. Furthermore, the early potentials (N1, P2 and P3-1) of the chemosensory event-related potential (CSERP) appeared with longer latencies when subjects received negative feedback. The state effects of helplessness resemble the deviations in the CSERP found in depressed patients, suggesting a general mood effect.     

Balloon Pulmonary Angioplasty (Percutaneous Transluminal Pulmonary Angioplasty) for Chronic Thromboembolic Pulmonary Hypertension: A Japanese Perspective

In recent years, therapeutic options for patients with chronic thromboembolic pulmonary hypertension (CTEPH) have expanded with the development of catheter-based interventional therapy, namely balloon pulmonary angioplasty (BPA), also called percutaneous transluminal pulmonary angioplasty. For CTEPH patients with technically inoperable disease or with an unfavorable risk-to-benefit ratio for surgical pulmonary endarterectomy, BPA is an important alternative therapeutic strategy. One important treatment goal of BPA should be the relief of pulmonary hypertension. However, the indications for BPA in specialized Japanese centers currently go beyond the sole indication of relieving pulmonary hypertension. BPA is currently limited to specific institutes and experienced operators, which allows better management of its associated complications of reperfusion pulmonary edema and vascular injury using various strategies based on past experiences. This article discusses the latest indications and treatment goals of BPA and the current flow diagram for therapeutic decision-making in CTEPH, and summarizes the factors to be considered when performing BPA, from a Japanese perspective.     

Is pulseless electrical activity a reason to refuse cardiopulmonary resuscitation with ECMO support?

Background

Cardiopulmonary resuscitation with ECMO support (ECPR) has shown to improve outcome in patients after cardiac arrest under resuscitation. Most current recommendations for ECPR do not include patients with a non-shockable rhythm such as PEA and asystole.