Functional lipidomics in patients on home parenteral nutrition: Effect of lipid emulsions

To investigate the fatty acid-based functional lipidomics of patients on long-term home parenteral nutrition receiving different intravenous lipid emulsions. METHODSA cross-sectional comparative study was carried out on 3 groups of adults on home parenteral nutrition (HPN), receiving an HPN admixture containing an olive-soybean oil-based intravenous lipid emulsion (IVLE) (OO-IVLE; n = 15), a soybean- medium-chain triacylglycerol-olive-fish oil-based IVLE (SMOF-IVLE; n = 8) or HPN without IVLE (No-IVLE; n = 8) and 42 healthy controls (HCs). The inclusion criteria were: duration of HPN ≥ 3 mo, current HPN admixtures ≥ 2 mo and HPN infusions ≥ 2/wk. Blood samples were drawn 4-6 h after the discontinuation of the overnight HPN infusion. The functional lipidomics panel included: the red blood cell (RBC) fatty acid (FA) profile, molecular biomarkers [membrane fluidity: saturated/monounsaturated FA ratio = saturated fatty acid (SFA)/monounsaturated fatty acid (MUFA) index; inflammatory risk: n-6/n-3 polyunsaturated fatty acid (PUFA) ratio = n-6/n-3 index; cardiovascular risk: sum of n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) = n-3 index; free radical stress: sum of FA trans isomers = %trans index] and FA pathway enzyme activity estimate (delta-9-desaturase = D9D; delta-6-desaturase = D6D; delta-5-desaturase = D5D; elongase = ELO). Statistics were carried out using nonparametric tests. The amount of each FA was calculated as a percentage of the total FA content (relative%). RESULTSIn the OO-IVLE group, the percentage of oleic acid in the RBCs was positively correlated with the weekly load of OO-IVLE (r = 0.540, P = 0.043). In the SMOF-IVLE cohort, the RBC membrane EPA and DHA were positively correlated with the daily amount of SMOF-IVLE (r = 0.751, P = 0.044) and the number of HPN infusions per week (r = 0.753; P = 0.046), respectively. The SMOF-IVLE group showed the highest EPA and DHA and the lowest arachidonic acid percentages (P < 0.001). The RBC membrane linoleic acid content was lower, and oleic and vaccenic acids were higher in all the HPN groups in comparison to the HCs. Vaccenic acid was positively correlated with the weekly HPN load of glucose in both the OO-IVLE (r = 0.716; P = 0.007) and the SMOF-IVLE (r = 0.732; P = 0.053) groups. The estimated activity of D9D was higher in all the HPN groups than in the HCs (P < 0.001). The estimated activity of D5D was lower in the SMOF-IVLE group than in the HCs (P = 0.013). The SFA/MUFA ratio was lower in all the HPN groups than in the HCs (P < 0.001). The n-6/n-3 index was lower and the n-3 index was higher in the SMOF-IVLE group in comparison to the HCs and to the other HPN groups (P < 0.001). The %trans index did not differ among the four groups. CONCLUSIONThe FA profile of IVLEs significantly influenced the cell membrane functional lipidomics. The amount of glucose in the HPN may play a relevant role, mediated by the insulin regulation of the FA pathway enzyme activities.

Emergence of New Injectable Lipid Emulsions in the USA: Guidance for Pediatric Clinicians

With the advent of new, particularly mixed-oil lipid emulsions approved by the United States Food & Drug Administration (FDA), clinicians have more options when choosing one as part of the parenteral nutrition support of patients. Lipid products long-standing availability in Europe and other parts of the world has certainly facilitated the process in the United States, where there was little evolution before 2014. These newer oil-based emulsions are finding their way to be used in pediatrics, as studies are being carried out that will result in pediatric labeling. Pediatric clinicians may find themselves wondering how these lipid emulsions are different from those that have come before;whether the same dosing or administration practices apply as with the traditional soybean-oil lipid emulsion, and if they can be used for other more emergent interventions. We present this review of the current lipid emulsions available in the U.S. market, highlighting the differences among them, as well as, providing some practical information for clinicians that can assist them in their day-to-day duties.

Tumor-targeting intravenous lipid emulsion of paclitaxel:Characteristics,stability,toxicity,and toxicokinetics

Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Lipid peroxidation: Its effects on the formulation and use of pharmaceutical emulsions

Pharmaceutical delivery systems are developed to improve the physicochemical properties of therapeutic compounds. Emulsions are one of these drug delivering systems formulated using water, oils and lipids as main ingredients. Extensive data are usually generated on the physical and chemical characteristics of these oil-in-water and lipid emulsions. However, the oxidative tendency of emulsions is often overlooked. Oxidation impacts the overall quality and safety of these pharmaceutical emulsions. Additionally, introducing oxidatively unstable emulsions into biological systems further promotes oxidation in situ. Products of these reactions then continue to pose serious harm to cells and fuel other physiological oxidation reactions. Consequently, the increase of oxidation products leads to oxidative damage to biological systems. Thus, emulsions with lower lipid peroxidation are more stable and will reduce the negative effects of oxidation in situ. Preventive measures during the formulation of emulsions are important. Many naturally occurring and cost effective substances possess low oxidation tendencies and confer oxidative protection when used in emulsions. Additionally,certain preparatory methods should be employed to reduce or better control lipid peroxidation.Finally, emulsions must be evaluated for their oxidation susceptibility using the various techniques available. Careful attention to the preparation of emulsions and assessment of their oxidative stability will help produce safer emulsions without compromising efficacy.

Lipid infusion and intravenous access in newborn infants

The spectacular development of neonatal intensive care since the 1960s allowed a drop in neonatal mortality of very-low-birth-weight （VLBW） infants from 50% to less than 15% in the last decade.

三种蛋白包覆纤维素纳米晶稳定皮克林乳液的构建及体外消化特性

纤维素纳米晶(CNCs)由于其表面固有的强亲水性,往往需要修饰改性才能应用,如乳液稳定。该文研究了三种蛋白(牛血清蛋白BSA、酪蛋白酸钠CAS和大豆分离蛋白SPI)通过静电修饰CNCs表面性质的可行性,并研究了其对CNCs乳液体外消化特性的影响。首先研究了pH值3.0时蛋白与CNCs的作用模式、吸附比例、颗粒结构特征,结果发现二者可以通过静电作用结合(Zeta电位由-35 mV至+20 mV),CNCs表面蛋白吸附比例由100%(蛋白浓度0~0.1%,m/V)逐渐降低至40%~60%(蛋白浓度0.5%,m/V)。静电修饰引起CNCs絮凝,显著改善其两亲性(接触角由35°增加至75°~80°)。然后研究了蛋白包覆CNCs的乳化性质,结果发现蛋白包覆CNCs形成了粒径为3~9μm的絮凝乳液,且凝聚稳定性更好,不同蛋白之间无显著差异。体外消化结果表明,与吐温20乳液(~90%)相比,蛋白包覆CNCs稳定乳液具有更低的游离脂肪释放率(~80%),蛋白种类影响不显著。可见,三种常见蛋白能够通过静电吸附方式修饰CNCs并将其转化为良好的Pickering稳定剂。该文研究结果能够极大丰富食品级皮克林稳定剂的来源,并促进相关功能乳液食品的开发。

淀粉脂质复合体的构建及其Pickering乳液性能表征

采用干法制备月桂酸、单月桂酸甘油酯、硬脂酸、单硬脂酸甘油酯的淀粉脂质复合体,并通过复合率、溶解率、膨胀力、碘吸收曲线、红外光谱、拉曼光谱、乳化性等对淀粉脂质复合体的性能进行表征。结果表明:4种淀粉脂质复合体的复合率随着脂肪酸碳链的增长而增大;溶解率和膨胀力总体上随着温度的升高逐渐变大,但随着碳原子数的增加而减小。碘吸收特性、红外光谱和拉曼光谱结果表明,随着碳原子数的增多,V型结晶淀粉与脂肪酸复合的效果越好。此外,利用质量浓度为8 g/L的淀粉脂质复合体制备的乳液具有较稳定的乳化状态。试验表明,淀粉脂质复合体在Pickering乳液中具有较大的应用潜力。

Incidence of Parenteral Nutrition-Associated Liver Disease in Infants on Prolonged Parenteral Nutrition with a Soybean-Based Lipid Emulsion: A 7-Year Experience

Parenteral nutrition associated liver disease (PNALD) is a significant complication in infants receiving long-term parenteral nutrition (PN). Chronic administration of PN has been associated with its development. Our purpose is to characterize our incidence of PNALD over an extended period and identify risk factors for its development, including administration of soybean-based injectable lipid emulsions (ILEs) as we transit to novel ILEs in our practice. Infants receiving 30 days or more of PN were included. PNALD was defined as a direct bilirubin ≥ 2 mg/dL. Data collected included: patient demographics, clinical and enteral feeding characteristics. Macronutrient intake was recorded using these cut-offs: glucose infusion rate (GIR) of ≤14 mg/kg/min or above, protein doses of ≤3 g/kg/day or above and lipid doses of ≤2 g/kg/day or above. A total of 349 infants were included, with an annual incidence of PNALD ranging between 34% - 54%. Infants with PNALD were younger by gestation (27 vs. 29.5 weeks) and smaller by birthweight (900 vs. 1248 grams). Sepsis, GI disease including necrotizing enterocolitis and bowel resection were significantly associated with an increased risk for development of PNALD. PNALD infants received lower protein doses (3.0 vs 3.3 g/kg/day, p = 0.014) while receiving higher GIR (11.4 vs 10.7 mg/kg/min, p = 0.012) compared to non-PNALD infants. Low birth weight, sepsis and bowel resection remain strong indicators of risk for PNALD. No single macronutrient increased our infants’ risk for PNALD. The use of newer ILEs when available should be evaluated for their impact on PNALD development.

Hypocaloric peripheral parenteral nutrition with lipid emulsion in postoperative gastrointestinal cancer patients

AIM:To investigate the use of lipid emulsion substitutingfor glucose in postoperative hypocaloric peripheral parenteral nutrition (HPPN).METHODS:This prospective, randomized study was conducted on 20 postoperative gastrointestinal cancer patients. They were randomized and equally divided into interventional group and control group, and both were administered isocaloric and isonitrogenous diets with for lipid emulsion substituting for partial glucose loads in the interventional group.RESULTS: Nutritional parameters and biochemical data were compared between the two groups before and after 6-d of HPPN. Most investigated variables showed no significant changes after administration of HPPN with lipid emulsion. However, the postoperative triglyceride level was significantly lower in the interventional group than in the control group (P < 0.05). In comparison with lipid emulsion, glucose administration resulted in less decrease in postoperative prealbumin level (P < 0.05).CONCLUSION: In addition to supplementing with essential fatty acid, it seems that HPPN with lipid emulsion is well-tolerated and beneficial to postoperative gastrointestinal cancer patients.

Ethanolic extract of cashew apple inhibits lipid metabolism and ameliorates obesity in atherogenic diet-induced obese rats

Objective:To evaluate the anti-obesity activity of ethanolic extract of cashew apple using various in vitro and in vivo models.Methods:Phytochemical screening was carried out in ethanolic extract of cashew apple,followed by quantification of phenol and flavonoid.Antioxidant potential was evaluated using 2,2-diphenyl-1-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)scavenging assays.The inhibitory effect of ethanolic extract of cashew apple on atic lipase was also studied.In addition,anti-obesity activity was determα-amylase and pancreined in two in vivo models,lipid emulsion model and atherogenic diet-induced obese rat model.Levels of postprandial plasma triglycerides were assessed in lipid emulsion model,whereas serum lipid profile,in vivo antioxidants and histopathological studies of the carotid artery and liver were performed in an atherogenic diet-induced obese model.Results:Phytochemical screening revealed the presence of carbohydrates,alkaloids,polyphenols,terpenoids,and steroids.The in vitro assays showed inhibition of otential.Ethanolic extract of cashew appα-amylase and pancreatic lipase and strong antioxidant ple showed significant and timedependent inhibitory activity on postprandial triglycerides after administration of lipid emulsion for 5 h.Ethanolic extract of cashew apple at 200 and 400 mg/kg on day 60 showed a significant reduction in body weight,body mass index and atherogenic index,whereas lipid profile and liver function marker levels in the serum were decreased in a dose-dependent manner at time intervals(day 0,20,40,and 60)compared to the atherogenic diet-induced obese rats.Histological observations showed reduced non-alcoholic fatty liver deposits and decreased atherosclerotic fatty streak plaques(carotid artery)after treatment with ethanolic extract of cashew apple.Conclusions:Ethanolic extract of cashew apple ameliorates obesity,which may be partly mediated by its delayed absorption of cholesterol and carbohydrates.

Bovine Serum Albumin Loaded Solid Lipid Nanoparticles Prepared by Double Emulsion Method

Solid lipid nanoparticles loaded with bovine serum albumin（BSA） were prepared by a double emulsion method. As the mass fraction of the model drug BSA increased from 0 to 15%, the particle size gradually increased. The physical stability of the nanoparticles was investigated by zeta potential measurement and they were shown to be quite stable. Fluorescence spectroscopy confirmed that the loaded position of BSA was on the interface between the inner aqueous phase and the solid lipid phase. Both Fourier-transform infrared spectroscopy and circular dichroism spectra indicate that BSA in the nanoparticles was not destroyed, but the secondary structure was disrupted slightly.

Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles： a magnetic resonance imaging study

Cholesterol-core nanoparticles （LDE） have been shown to be recognized by low-density lipoprotein receptors （LDLR） after administration; therefore, LDE is an ideal vehicle to deliver drug with targeting property. Paclitaxel, when incorporated into LDE, promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR. Here, we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR. Nineteen LDLR knockout male mice were fed 1% cholesterol for 12 weeks. Then, 12 animals received 4-weekly intraperitoneal LDE-paclitaxel （4 mg/kg） while 7 controls received saline solution. On week 12 and 16, in vivo MR/of the aortic roots was performed. Aorta macroscopy was made after euthanasia. Reduction ofatherosclerotic lesions was observed. LDE-paclitaxel treatment resulted in reduction of wall area （14%） and stenosis （22%） by MR/and 33% by macroscopy. Thus, LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.

淀粉基Pickering乳状液的稳定性及应用研究进展

基于淀粉基颗粒乳化剂具有安全可食、来源广且价格低等优点,综述了以淀粉微粒为颗粒乳化剂稳定的Pickering乳状液的制备及界面稳定机制的研究进展,分析了淀粉基Pickering乳状液中脂质氧化稳定性及其影响因素,展望了其在食品、医药和化妆品等行业的应用前景,并对相关存在的问题进行了分析,以期进一步促进相关基础理论的发展,并拓展乳状液的应用范围。

富含EPA/DHA结构脂高内相乳液的制备及其稳定性

考察了大豆分离蛋白与高酯果胶、壳聚糖复合后对富含EPA/DHA结构脂高内相乳液(HIPE)结构特性和稳定性的影响。实验结果表明:高酯果胶和壳聚糖可促进大豆分离蛋白对HIPE的稳定作用,形成倒置不流动的凝胶结构,油滴分布趋于均匀,平均粒径降低,乳液的弹性模量与黏性模量均得到增加,说明形成了以弹性为主的凝胶网状结构,且壳聚糖效果优于高酯果胶。所有的HIPE表现出良好的热稳定性,然而冻融稳定性差,壳聚糖可将其冻融稳定性提高到92.41%。综上,大豆分离蛋白和壳聚糖复合可制备稳定的富含EPA/DHA结构脂HIPE,作为乳脂替代品和特殊营养功能物质用于食品领域。

Effect of operation and different lipid emulsion on leukocyte chemiluminescence during operation in patients with gastrointestinal cancer

To observe the effect of operative trauma and lipid emulsion on leukocyte chemiluminescence (CL) during operation in patients with gastrointestinal cancer.Methods Twenty patients with advanced gastric cancer were divided into three groups:group 1,20% lipovenoes provided 30% nonprotein calories;group 2,20% lipofudingroup provided 30% nonprotein calories;group 3:glucose provided 100% nonprotein calories.Each group received full feeding with 25 kcal/kg every day,N 0.12 g/kg every day and were administered intravenously over 16～24 h as “all in one”.Preoperation,postoperation and after nutrition,the CL was determined.Results There was no significant difference in LC before and after operation.The LC in group 1 and group 2 was more brightened than that in group 3 4 days after TPN,but there was no significant difference in LC between group 1 and group 2.Conclusion (1) The operation trauma on the patients with gastric cancer has no significant effect on the LC.(2) TPN with lipid emulsion supplying 30% nonprotein calories can increase CL in patients with gastric cancer postoperation.5 refs,2 figs.

PCSK-9抑制剂联合他汀类药物早期强化降脂治疗对静脉溶栓疗效和预后的影响

急性缺血性脑卒中(AIS)发病早期进行静脉溶栓治疗是目前快速复通堵塞血管、恢复血流的最有效治疗方案,但有效血管的复通率有限,且手术时间依赖性强,临床上静脉溶栓术后出现颅内出血、脑水肿等并发症并不少见。早期针对AIS的危险因素尤其血脂水平进行处理,对促进静脉溶栓术后短期神经功能恢复及改善远期预后有显著的临床意义。目前临床上普遍推行以他汀类药物为主的强化降脂治疗,但近年来他汀类药物的不良反应及局限性逐渐显露。PCSK-9抑制剂是一种区别于他汀类药物靶点的新型降脂药物,具有优于他汀类药物的强化降脂作用,且暂未发现有任何肝脏毒性和不良反应,对于心脑血管疾病的治疗及预后也有积极影响。本文就近年来他汀类降脂治疗理念和血脂管理对缺血性脑卒中复发及预后的影响进行总结,并提出PCSK-9抑制剂在血脂调控方面的优势及其他多效性作用,为改善缺血性脑卒中患者静脉溶栓术后近期及远期预后提供新思路、新方法。

Management of acute carbamazepine poisoning:A narrative review

Standard management protocols are lacking and specific antidotes are unavailable for acute carbamazepine(CBZ)poisoning.The objective of this review is to provide currently available information on acute CBZ poisoning,including its management,by describing and summarizing various therapeutic methods for its treatment according to previously published studies.Several treatment methods for CBZ poisoning will be briefly introduced,their advantages and disadvantages will be analyzed and compared,and suggestions for the clinical treatment of CBZ poisoning will be provided.A literature search was performed in various English and Chinese databases.In addition,the reference lists of identified articles were screened for additional relevant studies,including non-indexed reports.Nonpeer-reviewed sources were also included.In the present review,154 articles met the inclusion criteria including case reports,case series,descriptive cohorts,pharmacokinetic studies,and in vitro studies.Data on 67 patients,including 4 fatalities,were reviewed.Based on the summary of cases reported in the included articles,the cure rate of CBZ poisoning after symptomatic treatment was 82%and the efficiency of hemoperfusion was 58.2%.Based on the literature review,CBZ is moderately dialyzable and the recommendation for CBZ poisoning is supportive management and gastric lavage.In severe cases,extracorporeal treatment is recommended,with hemodialysis as the first choice.

乳清蛋白微凝胶颗粒的制备及其对油脂消化性的抑制作用

针对高脂肪摄入带来的高血脂、高血压、高血糖等疾病风险,定向设计高脂肪食品的乳液结构,调控其与胃肠液的相互作用,从而减少食物中油脂的消化吸收,是实现饮食健康且不降低食物感官品质的有效途径。探究了不同pH值条件下,由乳清浓缩蛋白(WPC)通过湿热-均质组合方法制备的乳清蛋白微凝胶颗粒(WPMP)的理化性质(粒径分布、热力学性质、流变学性质等),并测定了加入WPMP的油脂乳液在消化道中的稳定性、游离脂肪酸(FFA)的释放率。结果表明:在pH值为5.5时,制备的WPMP具有相对较小的中位粒径6.63μm、较高的热稳定性、较小的流体指数(n=0.06)和较好的触变性(SR=0.42)。加入WPMP的油脂乳液的油滴粒径显著小于加入WPC的油脂乳液(P<0.05),且加入在pH值为5.5时制备的WPMP,可获得油滴粒径最小(13.28μm)的油脂乳液。相较于加入WPC制得的油脂乳液,WPMP油脂乳液在模拟胃肠消化液中具有更高的稳定性和更低的FFA释放率,且不同pH值条件下制备的WPMP油脂乳液具有不同的FFA释放率。研究证实,WPMP对消化道内胆盐界面取代、脂肪酶-辅脂酶界面吸附具有一定阻隔作用,因此,WPMP对油脂乳液的消化吸收具有一定的抑制作用,且受WPMP界面结构调控。希望研究结果可为定向设计乳液结构从而抑制油脂消化提供参考。

载脂蛋白E基因的多态性与缺血性脑卒中的发生及其治疗效果的相关研究

缺血性脑卒中目前严重影响着人们的生命健康,其发生、发展、治疗效果受多种因素共同影响。随着对缺血性脑卒中疾病的深入研究,人们对其相关致病基因也有了更深一步的了解,其中载脂蛋白E基因型更是近期研究热点,其基因型不仅参与了缺血性脑卒中的发生及发展,同时不同基因型的患者其治疗效果也具有差异性。本文就载脂蛋白E基因的多态性与缺血性脑卒中有关的脂质代谢、动脉粥样硬化的相关性以及不同基因型其溶栓、取栓、降脂等治疗效果的差异性进行系统性综述。

魔芋膳食纤维对油脂体外消化特性的影响

向油脂乳液中加入一定量魔芋膳食纤维,采用pH-stat法模拟油脂体外消化过程,考察魔芋膳食纤维对乳液在胃肠道中消化特性的影响,并研究乳液消化前后有效粒径、粒径分布、Zeta电位和微观结构的变化。结果表明,魔芋膳食纤维对乳液消化特性和消化前后理化性质产生显著性影响。随着纤维含量增加,乳液初始消化速率和最终消化程度均减小,含0.5%(质量分数)魔芋膳食纤维的乳液经胰脂肪酶消化120 min后脂肪酸释放率仅为14.84%;乳液粒径在体外消化的不同阶段逐渐增大,且同一消化阶段随纤维添加量增加而增大;肠消化后Zeta电位绝对值均大于40 mV,脂滴不稳定,发生聚集。脂肪乳液中脂质的最终消化率随体系中纤维添加量的增加而降低,该研究结果对胃肠道中脂质消化的控制及低热量功能食品的开发具有重要意义。