Search

Background: Using soybean oil–based lipid emulsions (Intralipid), which contain higher amounts of ω‐6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition–associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. Methods: The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late‐onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. Results: Forty‐four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] μmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. Conclusion: SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition. [ABSTRACT FROM AUTHOR]

The article "Impact of lipid emulsions in parenteral nutrition on platelets: a literature review" delves into the effects of lipid emulsions, including soybean oil-based and fish oil-based emulsions, on platelet function and aggregation in parenteral nutrition. It discusses the potential risks and benefits associated with different lipid emulsions in terms of platelet activity, emphasizing the need to understand these effects to minimize adverse outcomes and maximize protective benefits. The text also explores the impact of fish oil-based lipid emulsions on platelet function in healthy individuals and those at high thrombosis risk, highlighting changes in platelet structure, activation, and aggregation that may influence hemostasis. Additionally, the document underscores the importance of selecting the appropriate lipid emulsion for specific medical conditions to enhance patient outcomes in parenteral nutrition therapy. [Extracted from the article]

Abstract Background Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels. Objective To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34–36 weeks gestational age in infants born ≤ 750 g or

Clinical nutrition emulsions are important products that can be life-saving for many patients suffering from gastrointestinal tract disorders, swallowing impairment, cancer, liver diseases, and many other clinical conditions. The transfer of lipids to the human body can be either intravenously (Parenteral Nutrition, PN) or through the gastrointestinal tract (Enteral Nutrition, EN). PN emulsions are considered pharmaceuticals and thus regulated accordingly. On the other hand, EN emulsions are classified as Food for Specific Medical Purposes (FSMP) and do not follow pharmaceutical regulations. Regarding product design, PN emulsions must follow theoretical emulsion formulation and production aspects, but special requirements regarding droplet size distribution must be followed to comply with national pharmacopeia monographs. Furthermore, a full clinical program on clinical evidence to prove safety and efficacy must be provided for marketing approval. On the contrary, EN emulsions require limited clinical evidence to substantiate health or clinical benefits. A short introduction to clinical nutrition with a focus on lipid emulsions is presented in this chapter. Furthermore, a general overview of the composition and main ingredients of clinical nutrition lipid emulsions is reviewed. Main clinical aspects are also mentioned here, highlighting the difficulties of clinically proving the efficacy of these products. The manufacturing and control of clinical nutrition emulsions are also reviewed, focusing on PN products and the main regulatory requirements related to the safety of these intravenous emulsions. Finally, stability and physicochemical properties are reviewed, and examples of commercially available products are used to illustrate these properties linked to the stability of these products. Lipids in clinical nutrition is a moving field and we do hope this chapter may remain a valuable source to understand newly emerging research on this topic. [ABSTRACT FROM AUTHOR]

Background: Bilirubin neurotoxicity (BN) occurs in premature infants at lower total serum bilirubin levels than term infants and causes neurodevelopmental impairment. Usual dose lipid infusions in preterm infants may increase free fatty acids sufficiently to cause bilirubin displacement from albumin, increasing passage of unbound bilirubin (UB) into the brain leading to BN and neurodevelopmental impairment not reliably identifiable in infancy. These risks may be influenced by whether cycled or continuous phototherapy is used to control bilirubin levels. Objective: To assess differences in wave V latency measured by brainstem auditory evoked responses (BAER) at 34–36 weeks gestational age in infants born ≤ 750 g or < 27 weeks' gestational age randomized to receive usual or reduced dose lipid emulsion (half of the usual dose) irrespective of whether cycled or continuous phototherapy is administered. Methods: Pilot factorial randomized controlled trial (RCT) of lipid dosing (usual and reduced) with treatment groups balanced between cycled or continuous phototherapy assignment. Eligible infants are born at ≤ 750 g or < 27 weeks' gestational age enrolled in the NICHD Neonatal Research Network RCT of cycled or continuous phototherapy. Infants will randomize 1:1 to reduced or usual dose lipid assignment during the first 2 weeks after birth and stratified by phototherapy assignment. Free fatty acids and UB will be measured daily using a novel probe. BAER testing will be performed at 34–36 weeks postmenstrual age or prior to discharge. Blinded neurodevelopmental assessments will be performed at 22–26 months. Intention-to-treat analyses will be performed with generalized linear mixed models with lipid dose and phototherapy assignments as random effects covariates, and assessment for interactions. Bayesian analyses will be performed as a secondary analysis. Discussion: Pragmatic trials are needed to evaluate whether lipid emulsion dosing modifies the effect of phototherapy on BN. This factorial design presents a unique opportunity to evaluate both therapies and their interaction. This study aims to address basic controversial questions about the relationships between lipid administration, free fatty acids, UB, and BN. Findings suggesting a reduced lipid dose can diminish the risk of BN would support the need for a large multicenter RCT of reduced versus usual lipid dosing. Trial registration: Clinical Trials.gov, NCT04584983, Registered 14 October 2020, https://clinicaltrials.gov/ct2/show/NCT04584983 Protocol version: Version 3.2 (10/5/2022). [ABSTRACT FROM AUTHOR]

Background and Aim: Lipid peroxidation in parenteral nutrition mixtures is still a challenge. We aimed to evaluate the effect of two different amino acid solutions used in different clinical situations on lipid peroxidation of three different lipid emulsions (Intralipid, ClinOleic, and SMOFlipid) in all‐in‐one admixtures during 24 h of simulated infusion. The selected amino acid solutions included one used in stable patients and one used in renal insufficiency (Aminomel10E and Nephrotect, respectively). Methods: Eighteen all‐in‐one admixtures were prepared. The simulated infusion with light protection was conducted straight after the preparation for 24 h at room temperature. The lipid peroxidation process was evaluated in all‐in‐one admixtures and the original lipid emulsion by determining the malondialdehyde levels (high‐performance liquid chromatography) and conjugated dienes and trienes (ultraviolet‐visible spectrophotometry). Results: Malondialdehyde in the original packaging was lower in SMOFlipid (9 µM) compared with Intralipid (27 µM, P = 0.0003) and ClinOleic (25 µM, P = 0.0001). During simulated infusion, ClinOleic showed a significantly lower rate of lipid peroxidation (26% decrease in aldehyde levels) in comparison with Intralipid and SMOFlipid (up to 39% and 31% increase in aldehyde levels, respectively) when the admixture was based on Aminomel10E. In admixtures based on Nephrotect, ClinOleic, and SMOFlipid showed better oxidative stability in comparison with Intralipid. Admixtures based on Nephrotect and Intralipid had higher levels of primary lipid peroxidation products than those based on ClinOleic (P = 0.030) or SMOFlipid (P = 0.071, not significant). Conclusions: Amino acid solutions influence the rate of lipid peroxidation. The observation should be confirmed in larger studies with different amino acid solutions. [ABSTRACT FROM AUTHOR]

Objective: Total parenteral nutrition (TPN) is very important for providing optimal nutrition during the critical developmental period of preterm newborns. Thus, there is a need to optimize TPN solutions to reduce morbidities. This study aimed to examine the effects of olive oil (ClinOleic®) and fish oil (SMOFlipid®) therapies on the frequencies of neonatal morbidities. Methods: Premature newborns hospitalized in the neonatal intensive care unit and receiving TPN for at least 14 days were included in the study. Newborns who were hospitalized and received olive oil-based lipid (ClinOleic®) were included in the olive oil group, and those who received omega-3 containing multi-lipid (SMOFlipid®) were included in the SMOFlipid group. Results: This study enrolled a total of 222 very-low-birth-weight premature newborns. The breastfeeding rate in the olive oil group was significantly lower than that in the SMOFlipid group (p

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

Abstract Background Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness worldwide. This study aimed to investigate whether supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) in parenteral nutrition may have beneficial effects on ROP in preterm infants. Methods A total of 89 preterm infants, admitted to Neonatal Intensive Care Unit (NICU) in Anhui Provincial Children’s Hospital from September 2017 to August 2020, were recruited in the study. Based on the medical documents, the subjects were categorised into two groups: administration of the fish oil emulsion (n=43) containing soy oil, medium-chain-triglycerides (MCT), olive oil and fish oil (6g/dL, 6g/dL, 5g/dL and 3g/dL respectively), and the soy oil emulsion (n=46) containing 10g/dL of soy oil and MCT each. At 4 weeks of hospitalization, ROP was screened and diagnosed. Fatty acids in erythrocytes were determined using gas chromatography. Results The averaged birth weight and gestational age were 1594±296 g and 31.9±2.3 wk, 1596±263 g and 31.6±2.3 wk respectively for preterm infants in the fish oil group and soy oil group. After 4 to 6 weeks of hospitalization, among all the preterm infants, 52 developed ROP (all stages) indicating an incidence of ROP at 58.43%. Although the incidence of ROP with any stages showed no differences between the two groups, the severe ROP incidence in the group with fish oil emulsions (2.33%) was significantly lower than that in the group with soy oil emulsions (23.91%) (P

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous‐lipid‐emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5 mg kg−1 was administered in 24 pigs, and 3 min later, the animals received ILE: 1.5 ml kg−1 + 0.25 ml kg−1 min−1 (ILE group); sodium bicarbonate: 2 mEq kg−1 + 1 mEq kg−1 h−1 (NaHCO3 group); saline solution (CTL group). Electrophysiological parameters were evaluated for 30 min. The area under the curve (AUC) for the first 5 or 30 min was compared between groups. Ropivacaine induced a lengthening of the PR interval by 17% (P = 0.0001), His‐ventricle‐interval by 58% (P = 0.001), sinus QRS complex by 56% (P = 0.0001), paced QRS at 150 bpm by 257% (P = 0.0001), and at 120 bpm by 143% (P = 0.0001) in all groups. At 5 min after treatment, sinus QRS in the NaHCO3 group was shorter than that in the CTL group (AUCQRS5, P = 0.003) or ILE group (AUCQRS5, P = 0.045). During the first minute, seven of the animals in the NaHCO3 group vs. two in the ILE or 0 in the CTL group recovered more than 30% of the sinus QRS previously lengthened by ropivacaine (P = 0.003). Sodium bicarbonate reversed the electrophysiological toxicity of ropivacaine faster than ILE and control groups. [ABSTRACT FROM AUTHOR]

Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model. [ABSTRACT FROM AUTHOR]

Abstract Background Tenfold or more overdose of a drug or preparation is a dreadful adverse event in neonatology, often due to an error in programming the infusion pump flow rate. Lipid overdose is exceptional in this context and has never been reported during the administration of a composite intravenous lipid emulsion (ILE). Case presentation Twenty-four hours after birth, a 30 weeks’ gestation infant with a birthweight of 930 g inadvertently received 28 ml of a composite ILE over 4 h. The ILE contained 50% medium-chain triglycerides and 50% soybean oil, corresponding to 6 g/kg of lipids (25 mg/kg/min). The patient developed acute respiratory distress with echocardiographic markers of pulmonary hypertension and was treated with inhaled nitric oxide and high-frequency oscillatory ventilation. Serum triglyceride level peaked at 51.4 g/L, 17 h after the lipid overload. Triple-volume exchange transfusion was performed twice, decreasing the triglyceride concentration to

L'hépatopathie liée à la nutrition parentérale impacte négativement le pronostic des patients insuffisants intestinaux, par son évolution possible vers la cirrhose et l'insuffisance hépatique. Ses facteurs de risque sont multiples, mais la composition de la nutrition parentérale et l'insuffisance intestinale sous-jacente jouent probablement un rôle majeur. Cette complication est très certainement sous-diagnostiquée, et il n'existe pas à ce jour de définition consensuelle de cette pathologie. Actuellement, son diagnostic repose essentiellement sur un faisceau d'arguments biologiques, radiologiques et/ou histologiques, en absence de diagnostic différentiel. Son traitement est majoritairement fondé sur la prévention, en repérant les patients à risque, notamment les patients ayant un syndrome de grêle court ; en adaptant les apports glucido-lipidiques et la composition des émulsions lipidiques ; et en traitant précocement les complications infectieuses, qu'elles soient liées aux accès veineux ou à une translocation bactérienne. À l'avenir, des études supplémentaires sont nécessaires pour mieux comprendre les mécanismes physiopathologiques de cette complication, proposer une stratégie diagnostique, un suivi adapté et des axes thérapeutiques préventifs et curatifs innovants. Hepatopathy related to parenteral nutrition, because of its possible evolution towards cirrhosis and liver failure, has a negative impact on the prognosis of patients with intestinal failure. The pathogenesis of this complication is multifactorial, ranging from the composition of the parenteral nutrition to the length of the remaining small intestine, and to date there is no consensual definition. Its diagnosis is essentially based on a range of biological, radiological and/or histological arguments. Its treatment is based on prevention, identification of risk factors, adaptation of carbohydrate-lipid intake and the composition of lipid emulsions and the earliest possible management of any sepsis, related to venous access or bacterial translocation. In the future, additional studies are needed to better understand the pathophysiological mechanisms of this complication, to propose a diagnostic strategy, adapted follow-up and innovative preventive and curative therapies. [ABSTRACT FROM AUTHOR]

Ropivacaine is considered to have a wider margin of cardiovascular safety. However, several reports of ventricular arrhythmias (VA) due to ropivacaine toxicity have been documented. Intravenous lipid emulsions (ILEs) have recently been used successfully in the treatment of local anesthetic intoxication. The main objective of the present study was to evaluate the efficacy of the ILEs in the prevention of pacing-induced-VA and electrophysiological alterations in an animal model of ropivacaine toxicity. Nineteen pigs were anesthetized and instrumentalized. A baseline programmed electrical ventricular stimulation protocol (PEVSP) to induce VA was performed. Ropivacaine (5 mg·kg−1 + 100 μg·kg−1·min−1) followed by normal saline infusion (control group n = 8) or intralipid 20% (1.5 mL·kg−1 + 0.25 mL·kg−1·min−1) for the ILE group (n = 8), were administered three minutes after the ropivacaine bolus. PEVSP was repeated 25 min after the onset of ropivacaine infusion. Pacing-induced VA and electrophysiological abnormalities were assessed in both groups. A sham-control group (n = 3) without ropivacaine infusion was included. Most of the electrophysiological parameters evaluated were affected by ropivacaine: PR interval by 28% (p = 0.001), AV interval by 40% (p = 0.001), sinus QRS by 101% (p = 0.001), paced QRS at a rate of 150 bpm by 258% (p = 0.001), and at 120 bpm by 241% (p = 0.001). Seven animals (87.5%) in the control group and eight animals (100%) in the ILE group developed sustained-VA (p = 0.30). Successful resuscitation occurred in 100% of animals in the ILE group vs. 57% of animals in the control group, p = 0.038. Pacing-induced-VA terminated at the first defibrillation attempt in 75% of the animals in the ILE group vs. 0% in the control group, p = 0.01. Ropivacaine strongly altered the parameters of ventricular conduction, thus facilitating the induction of VA. ILEs did not prevent pacing-induced VA. However, facilitated resuscitation and termination of VA were delivered at the first defibrillation attempt compared to the control group. [ABSTRACT FROM AUTHOR]

Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven®) emulsion vs. a high amount of ω6 fatty acids (Intralipid®) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven® prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven® addition. Interestingly, the study's findings contradict previous studies and revealed that Omegaven® at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium. [ABSTRACT FROM AUTHOR]

The local anesthesics are defined as medicaments that block the generation and spread of impulses in excitable fabrics, from bony marrow, nervous roots, peripheral nerves or other excitable fabrics as cardiac muscle, smooth muscle and brain. The systemic intoxication takes place due to the plasmatic concentrations raised after high doses or the intravenous inadvertent administration. The increasing use of technologies of anesthesia locorregional forces to bear in mind the systemic intoxication for local anesthesics as an anesthesic complication of low incident, but high morbi-mortality, beside constituting one of the more frequent reasons of cardiorespiratory unemployment of anesthesic origin. The clinical presentation of this complication is very variable and includes a great spectrum of symptoms related principally to the neurological and cardiovascular toxicity. Though infrequent, the reactions can be very serious, and to result in irreversible hurt or death of the patient. The prevention seems to have diminished the poisoning of the local anesthesics and is more effective than the treatment. The managing is based on measures of resuscitation cardiopulmonar advanced, the pharmacological treatment and the precocious employment of the lipid emulsions. I present a case of systemic intoxication using lidocaine simply as anesthesic local only one during the accomplishment of blockade of peripheral nerve in elective surgery. [ABSTRACT FROM AUTHOR]

Copyright of Medeniyet Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Despite the successful treatment of drug intoxications, little information is available to quantitively predict the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules. We defined two new parameters, drug accommodation capacity and drug capture kinetics, to characterize the drug capture capability of lipid emulsions. By precisely characterizing their drug capture capability, the effect of lipid emulsions on pharmacokinetic features of overdosed drug molecules was quantitively described. This quantitative description enabled an accurate prediction of the reducing extent on the half-life and area under drug concentration-time curve, which was verified by the successful treatment of overdosed propafenone. Moreover, the capture effect prediction using drug capture capability was more accurate than that of directly using log P. Overall, the developed capture capability accurately described the effect of lipid emulsions on drug pharmacokinetic features, which can guide the clinical application of lipid emulsions for the treatment of drug overdose. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness worldwide. This study aimed to investigate whether supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs) in parenteral nutrition may have beneficial effects on ROP in preterm infants.Methods: A total of 89 preterm infants, admitted to Neonatal Intensive Care Unit (NICU) in Anhui Provincial Children's Hospital from September 2017 to August 2020, were recruited in the study. Based on the medical documents, the subjects were categorised into two groups: administration of the fish oil emulsion (n=43) containing soy oil, medium-chain-triglycerides (MCT), olive oil and fish oil (6g/dL, 6g/dL, 5g/dL and 3g/dL respectively), and the soy oil emulsion (n=46) containing 10g/dL of soy oil and MCT each. At 4 weeks of hospitalization, ROP was screened and diagnosed. Fatty acids in erythrocytes were determined using gas chromatography.Results: The averaged birth weight and gestational age were 1594±296 g and 31.9±2.3 wk, 1596±263 g and 31.6±2.3 wk respectively for preterm infants in the fish oil group and soy oil group. After 4 to 6 weeks of hospitalization, among all the preterm infants, 52 developed ROP (all stages) indicating an incidence of ROP at 58.43%. Although the incidence of ROP with any stages showed no differences between the two groups, the severe ROP incidence in the group with fish oil emulsions (2.33%) was significantly lower than that in the group with soy oil emulsions (23.91%) (P<0.05). After 14 days of nutrition support, the preterm infants administered fish oil emulsions had an increase in erythrocyte DHA content, with a reduction in ratio of arachidonic acid (AA) to DHA and an increase of n-3 index.Conclusion: Supplementation of n-3 PUFAs through parenteral fish oil containing lipid emulsions resulted in an increase in erythrocyte DHA, and this might have beneficial effects on prevention of severe ROP in preterm infants. [ABSTRACT FROM AUTHOR]

Home parenteral nutrition (HPN) is a life-sustaining therapy for individuals with intestinal failure in a community setting. It refers to the intravenous infusion of macronutrients, micronutrients, fluids and electrolytes. Routinely used HPN solutions contain different quantities of these components. Consequently, each HPN solution may have different impacts on metabolism, inflammation and oxidative stress. Long-term use of HPN can lead to a number of adverse health outcomes including the development of metabolic bone disease, intestinal failure associated liver disease and poor quality of life but whether, and how, the composition of HPN solutions contributes to these health sequelae is poorly understood. The aim of this study is to systematically review and evaluate the evidence for the differential effects of HPN solutions and to understand what features are associated with differences in clinical endpoints. A systematic literature search was conducted between September and December 2020, and updated in July 2021 using the MEDLINE (Ovid), EMBASE, Scopus, and Web of Science databases. Studies were selected according to the following criteria (a) adult participants (>18 years old) dependent on HPN; (b) randomised controlled trials, prospective cohort and cross-sectional study designs; (c) primary research comparing two or more HPN solutions and (d) published in English language. Data were extracted and study quality assessed using Cochrane Collaboration's tools: Risk of Bias for Randomised Controlled Trials (RCTs); Risk of Bias in Non-Randomised Studies of Interventions; and the Newcastle Ottawa Scale for cross-sectional studies. Of the 5148 articles identified, seven RCTs, two prospective cohort and one cross-sectional study were included with a total of 295 participants. Studies varied in terms of duration (one to 60 months) and sample size (n = 5 to 88). Ten studies compared lipid emulsions (LE) and one study also compared LE with lipid-free HPN. No studies were found that compared the amino acid, vitamin, trace element or electrolyte components of HPN. In general, LE were well tolerated with no significant adverse effects. LE containing olive +/or fish oil were associated with a lower ω-6:ω-3 fatty acid ratio, positive reductions in markers of liver function, and changes in blood and cell fatty acid profiles. Despite the increasing use of HPN, there is surprisingly little evidence available to guide the provision of macro and micronutrients in the adult population requiring this therapy. Although LE containing olive +/or fish oil show promise with regards to liver function and blood and cell fatty acid profiles, further studies are needed before drawing definitive conclusions on the clinical value of these emulsions. It is likely that one type of HPN solution alone cannot be uniformly applied to patient care, and each patient should be assessed on an individual basis. [ABSTRACT FROM AUTHOR]

Background: Tenfold or more overdose of a drug or preparation is a dreadful adverse event in neonatology, often due to an error in programming the infusion pump flow rate. Lipid overdose is exceptional in this context and has never been reported during the administration of a composite intravenous lipid emulsion (ILE).Case Presentation: Twenty-four hours after birth, a 30 weeks' gestation infant with a birthweight of 930 g inadvertently received 28 ml of a composite ILE over 4 h. The ILE contained 50% medium-chain triglycerides and 50% soybean oil, corresponding to 6 g/kg of lipids (25 mg/kg/min). The patient developed acute respiratory distress with echocardiographic markers of pulmonary hypertension and was treated with inhaled nitric oxide and high-frequency oscillatory ventilation. Serum triglyceride level peaked at 51.4 g/L, 17 h after the lipid overload. Triple-volume exchange transfusion was performed twice, decreasing the triglyceride concentration to < 10 g/L. The infant's condition remained critical, with persistent bleeding and shock despite supportive treatment and peritoneal dialysis. Death occurred 69 h after the overdose in a context of refractory lactic acidosis.Conclusions: Massive ILE overdose is life-threatening in the early neonatal period, particularly in premature and hypotrophic infants. This case highlights the vigilance required when ILEs are administered separately from other parenteral intakes. Exchange transfusion should be considered at the first signs of clinical or biological worsening to avoid progression to multiple organ failure. [ABSTRACT FROM AUTHOR]

The article presents pathophysiology, clinical picture and management of yew poisoning. Authors present also their own experiences with treating yew poisoning with fat emulsion. Plants of the yew genus, of which in Europe predominates Taxus baccata, are well known for their toxic properties. Particularly high concentrations of poisonous alkaloids are present in the needles of this evergreen and highly popular decorative plant. The danger associated with accidental or intentional ingestion of yew is primarily related to the cardiotoxic effects of the alkaloids (taxine A and B). Taxine B shows a much stronger toxic effect on the heart than taxine A. It affects atrio-ventricular conduction, what may result in a widening of the QRS complexes, atrio-ventricular blocks (A-V) of II/III degree and even in asystole. Yew poisoning is relative rare and evidence-based treatment guidelines on management of such poisoning is hard to prepare. The first-line treatement should base on suportive therapy. In some cases extracorporeal life support therapies such veno-arterial ECMO should be consider. There are also premise based on case reports and mechanism of action that the use of fat emulsion may be effective rescue treatment.

Parenteral nutrition (PN) can supply all essential nutrients to a patient with gastrointestinal insufficiency. However, the sensitivity to lipid peroxidation might increase in those receiving PN, especially home parenteral nutrition (HPN). This study aimed to investigate whether PN affects the antioxidant balance of plasma of HPN patients without comorbidities and whether this balance is influenced by comorbidities and according to the type of lipid emulsion included in the PN. Adult patients on HPN (n = 86) received one of three types of lipid emulsion (based on 1) soyabean oil, 2) olive and soyabean oil or 3) soyabean, coconut, olive and fish oil) in all-in-one mixtures; in addition healthy controls (n = 66) were studied as comparators. HPN patients were classified to the following subgroups: 1) patients without (n = 58) or with (n = 28) comorbidities 2) patients on Intralipid (G INTRA , n = 53), ClinOleic (G CLIN , n = 17) or SMOFlipid (G SMOF n = 16). The activities of total glutathione peroxidase (GSH-Px), selenium dependent glutathione peroxidase (Se-GSHPx) and glutathione S-transferase (GST) in plasma were determined spectrophotometrically. The antioxidant potential of plasma was determined using oxygen radical absorbance capacity (ORAC). The lipid peroxidation marker malondialdehyde (MDA) was analyzed with high performance liquid chromatography. MDA concentration was the highest in G INTRA and the lowest in G SMOF (p < 0.05). G SMOF also had the highest activity of GSH-Px. No differences in Se-GSHPx, GST and ORAC were observed among G INTRA , G CLIN and G SMOF. Comparing with healthy controls, significantly lower GST (p = 0.0293) and ORAC (p < 0.0001) were observed in the HPN patients. Among all measured parameters only the concentration of MDA was significantly higher in patients with comorbidities compared to those without them. Comorbidities did not influence MDA level in G INTRA and G SMOF being still the lowest in G SMOF (p = 0.0033). In contrast, significantly higher MDA level was observed for G CLIN in those with vs. without comorbidities (p = 0.0262). Patients on HPN have lower antioxidant defenses than healthy controls. The type of lipid emulsion used in HPN affects lipid peroxidation (even after taking into account comorbidities which often involve oxidative stress) being the highest in G INTRA and the lowest in G SMOF. Thus, to minimize the risk of oxidative stress, SMOFlipid can be considered in patients in HPN especially for those with comorbidities. ClinOleic can be considered in HPN patients without comorbidities. The observation should be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Fat emulsions are extremely important for newborns, especially for seriously ill, premature babies with very low and extremely low body weight (congenital or acquired pathology that causes gastrointestinal failure), if routine enteral feeding is problematic and sometimes impossible. All current updated data on the quality, efficacy and feasibility of using lipid emulsions in parenteral nutrition for medical reasons were published in the 2019 Cochrane Review “Systematic review of lipid emulsions for intravenous nutrition in term and late preterm infants”. More recently, fatty emulsions obtained from several sources have become available for clinical use. SMOFLipid is one of such fat emulsion. It`s a mixture of soybean oil, medium-chain triglycerides, olive oil and fish oil in a 30: 30: 25: 15 ratio that has certain benefits. Due to the content of medium-chain triglycerides, it`s rapidly metabolized; soybean oil - a source of polyunsaturated fatty acids; olive oil - less immune effects; and fish oil - the antiinflammatory effect is enhanced, and a decrease in the frequency of bronchopulmonary dysplasia and infection in premature infants is noted. Today in Ukraine, to cover the needs for energy, calories, and essential fatty acids in term and premature babies, when oral or enteral nutrition is not possible, insufficient or contraindicated, lipid emulsion SMOFLipid is actively used as part of total parenteral nutrition. The general dynamics of prescribing lipid emulsions in Ukraine are regressive due to certain regions, where the practice of parenteral nutrition for newborns differs from other areas in sporadicity and less priority due to objective and subjective circumstances. One of the key ways to solve the problem of improving the quality of medical care for newborns in neonatal hospitals should be the introduction of a training system (seminars, practical training, etc.) for neonatologists in modern principles of conducting and international clinical guidelines for parenteral nutrition of newborns at all levels in all regions. Ukraine.

Lipid emulsions (LEs), an integral component in parenteral nutrition (PN) feeding, have shifted from the primary aim of delivering non-protein calories and essential fatty acids to defined therapeutic outcomes such as reducing inflammation, and improving metabolic and clinical outcomes. Use of LEs in PN for surgical and critically ill patients is particularly well established, and there is enough literature assigning therapeutic and adverse effects to specific LEs. This narrative review contrarily puts into perspective the fatty acid compositional (FAC) nature of LE formulations, and discusses clinical applications and outcomes according to the biological function and structural functionality of fatty acids and co-factors such as phytosterols, α-tocopherol, emulsifiers and vitamin K. In addition to soybean oil-based LEs, this review covers clinical studies using the alternate LEs that incorporates physical mixtures combining medium- and long-chain triglycerides or structured triglycerides or the unusual olive oil or fish oil. The Jaded score was applied to assess the quality of these studies, and we report outcomes categorized as per immuno-inflammatory, nutritional, clinical, and cellular level FAC changes. It appears that the FAC nature of LEs is the primary determinant of desired clinical outcomes, and we conclude that one type of LE alone cannot be uniformly applied to patient care.

Objective: The presence of phytosterols in vegetal lipid emulsions has been associated with alterations of liver function tests. Determination of phytosterols content, currently undeclared, would allow the development of strategies to prevent or treat these alterations. Method: 3-4 non-consecutive batches of 6 lipid emulsions from different providers (Clinoleic, Intralipid, Lipofundina, Lipoplus, Omegaven and Smoflipid) were analyzed. Differences in total phytosterol assay between providers and batches were statistically studied by a one-way ANOVA and Kruskal-Wallis non-parametric approximation and post hoc Scheffé test (p < 0.05) Results: The absence of phytosterols was confirmed in Omegaven, emulsion based on fish oil. The highest assay of phytosterols (422.4 ± 130.5 μg/mL) has been related with the highest percentage of soya bean oil in Intralipid. In the remaining emulsions, concentrations were from 120 to 210 μg/mL related to the percentage of soya bean oil. Statistically significant differences of phytosterol content in lipid emulsions were observed among different providers (F = 23.59; p = 0.000) as well as among non-consecutive batches. Clinolenic (F = 23.59; p = 0.000), Intralipid (F = 978.25; p = 0.000), Lipofundina TCL/TCM (F = 5.43; p = 0.045), Lipoplus (F = 123.53; p = 0.000) and Smoflipid (16.78; p = 0.000). Except for Lipofundina TCL/TCM, the differences between batches were marked. Conclusions: Lipid emulsions, registered on Spanish pharmaceutical market, contain variable quantities of phytosterols dependent on commercial brand and batch

Background: SMOFlipid has a more diverse lipid profile than traditional Intralipid and has become the standard lipid for patients in our intestinal rehabilitation program. Our objective was to compare outcomes in neonates with intestinal failure (IF) who received SMOFlipid against those receiving Intralipid.Methods: This was a retrospective cohort study of infants with IF with a minimum follow-up of 12 months in 2008-2016. Patients were stratified into 2 groups: group 1 received SMOFlipid; group 2 was a historical cohort who received Intralipid. The primary outcome was liver function evaluated using conjugated bilirubin (CB) levels. Statistical analysis included the Mann-Whitney U and χ2 tests, with an α value < 0.05 considered significant. Approval was obtained from our institutional review board.Results: Thirty-seven patients were evaluated (17 = SMOFlipid, 20 = Intralipid). SMOFlipid patients were less likely to reach CB of 34 (24% vs 55%, P = 0.05), 50 µmol/L (11.8% vs 45%; P = 0.028), and did not require Omegaven (0% vs 30%; P = 0.014). CB level at 3 months after initiation of parenteral nutrition (PN) was lower in patients receiving SMOFlipid (0 vs 36 µmol/L; P = 0.01). Weight z-scores were improved for patients receiving SMOFlipid at 3 months (-0.932 vs -2.092; P = 0.028) and 6 months (-0.633 vs -1.614; P = 0.018). There were no differences in PN-supported patients or demographics between the groups.Conclusion: Use of SMOFlipid resulted in decreased development of IF-associated liver disease in patients with IF when assessed using biochemical tests. [ABSTRACT FROM AUTHOR]

Lipid emulsions (LEs), an integral component in parenteral nutrition (PN) feeding, have shifted from the primary aim of delivering non-protein calories and essential fatty acids to defined therapeutic outcomes such as reducing inflammation, and improving metabolic and clinical outcomes. Use of LEs in PN for surgical and critically ill patients is particularly well established, and there is enough literature assigning therapeutic and adverse effects to specific LEs. This narrative review contrarily puts into perspective the fatty acid compositional (FAC) nature of LE formulations, and discusses clinical applications and outcomes according to the biological function and structural functionality of fatty acids and co-factors such as phytosterols, α-tocopherol, emulsifiers and vitamin K. In addition to soybean oil-based LEs, this review covers clinical studies using the alternate LEs that incorporates physical mixtures combining medium- and long-chain triglycerides or structured triglycerides or the unusual olive oil or fish oil. The Jaded score was applied to assess the quality of these studies, and we report outcomes categorized as per immuno-inflammatory, nutritional, clinical, and cellular level FAC changes. It appears that the FAC nature of LEs is the primary determinant of desired clinical outcomes, and we conclude that one type of LE alone cannot be uniformly applied to patient care. [ABSTRACT FROM AUTHOR]

As the global population ages, the prevalence of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease and stroke continues to increase. Therefore, it is necessary to develop preventive and therapeutic methods against neuroinflammatory diseases. Lipofundin is a lipid emulsion commonly used in clinical anesthetic solvents and nutritional supplements. Lipid emulsions have been shown to possess anti-inflammatory properties. However, the potential beneficial effect of lipofundin against neuroinflammation requires elucidation. In the present study, two cell models were used to investigate the efficacy of lipofundin against neuroinflammation. In the first model, BV2 mouse microglial cells were treated with lipopolysaccharide (LPS) to induce nitric oxide (NO) production as a model of neuroinflammation. In the second model, HMC3 human microglial were activated by LPS, and changes in the secretion of factors associated with inflammation were analyzed using Luminex xMAP® technology. Griess assay results revealed that lipofundin significantly prevented and treated LPS-induced NO production. An anti-neuroinflammatory effect was also observed in HMC3 cells, where lipofundin exhibited excellent preventive and therapeutic properties by reducing the LPS-induced expression and secretion of interleukin-1β. Notably, lipofundin also promoted the secretion of certain growth factors, suggesting a potential neuroprotective effect. These results demonstrate that, in addition to its role as a solvent for drugs and nutritional support, lipofundin may also have beneficial effects in alleviating the progression of neuroinflammation. These findings may serve as an important reference for future translational medicine applications. [ABSTRACT FROM AUTHOR]

Bo Zhang,1 Yunmei Song,2 Tianqi Wang,1 Shaomei Yang,1 Jing Zhang,1 Yongjun Liu,1 Na Zhang,1 Sanjay Garg2 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong Province, People’s Republic of China; 2Centre for Pharmaceutical Innovation and Development (CPID), School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia Abstract: Combinational nanomedicine is becoming a topic of much interest in cancer therapy, although its translation into the clinic remains extremely challenging. One of the main obstacles lies in the difficulty to efficiently co-deliver immiscible hydrophilic/hydrophobic drugs into tumor sites. The aim of this study was to develop co-loaded lipid emulsions (LEs) to co-deliver immiscible hydrophilic/hydrophobic drugs to improve cancer therapy and to explore the co-delivery abilities between co-loaded LEs and mixture formulation. Multiple oxaliplatin/irinotecan drug–phospholipid complexes (DPCs) were formulated. Co-loaded LEs were prepared using DPC technique to efficiently encapsulate both drugs. Co-loaded LEs exhibited uniform particle size distribution, desired stability and synchronous release profiles in both drugs. Co-loaded LEs demonstrated superior anti-tumor activity compared with the simple solution mixture and the mixture of single-loaded LEs. Furthermore, co-loaded nanocarriers could co-deliver both drugs into the same cells more efficiently and exhibited the optimized synergistic effect. These results indicate that co-loaded LEs could be a desired formulation for enhanced cancer therapy with potential application prospects. The comparison between co-loaded LEs and mixture formulation is significant for pharmaceutical designs aimed at co-delivery of multiple drugs. Keywords: cancer, combination therapy, co-delivery, lipid emulsions, drug–phospholipid complex

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed.

A number of topics important to the handling of intravenous lipid emulsions (ILEs) were discussed at the international summit. ILE handling includes the preparation and the administration steps in the typical use of parenteral nutrition (PN). The discussion and consensus statements addressed several issues, including standardization of the PN process, use of commercially available multi-chamber PN or compounded PN bags, the supervision by a pharmacist with expertise, limiting ILE repackaging, and infusion duration. [ABSTRACT FROM AUTHOR]

Unintentional administration of bupivacaine may be associated with electrocardiogram changes that promote the development cardiac arrhythmias. Ventricular repolarization markers (corrected QT, QT dispersion, Tpeak–Tend and Tpeak–Tend dispersion) are useful to predict cardiac arrhythmias. We aim to investigate the effects of bupivacaine on the transmural dispersion of repolarization and their reversion following intravenous lipid emulsion (ILE) administration. Fourteen pigs were anaesthetized with thiopental and sevoflurane and underwent tracheal intubation. After instrumentation, a 4 mg kg-bolus of bupivacaine was administrated followed by an infusion of 100 µg kg−1 min−1. QT interval, QTc:QT corrected by heart rate, Tpeak-to-Tend interval and QT and Tpeak-to-Tend dispersion were determined in a sequential fashion: after bupivacaine (at 1 min, 5 min and 10 min) and after ILE (1.5 mL kg−1 over 1 min followed by an infusion of 0.25 mL kg−1 min−1). Three additional animals received only ILE (control group). Bupivacaine significantly prolonged QT interval (∆:36%), QT dispersion (∆:68%), Tpeak-to-Tend (∆:163%) and Tpeak-to-Tend dispersion (∆:98%), from baseline to 10 min. Dispersion of repolarization was related to lethal arrhythmias [three events, including asystole, sustained ventricular tachycardia (VT)] and repeated non-sustained VT (4/14, 28%). A Brugada-like-ECG pattern was visualized at V1–4 leads in 5/14 pigs (35%). ILE significantly decreased the alterations induced by bupivacaine, with the termination of VT within 10 min. No ECG changes were observed in control group. Bupivacaine toxicity is associated with an increase of transmural dispersion of repolarization, the occurrence of a Brugada-like pattern and malignant VA. ILE reverses the changes in dispersion of repolarization, favouring the disappearance of the Brugada-like pattern and VT. [ABSTRACT FROM AUTHOR]

Copyright of Medicina Neotloznyh Sostoanij is the property of Zaslavsky O.Yu and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: There is evidence from laboratory and animal studies that fish oil-containing intravenous lipid emulsions (FOC-IVLEs) have a beneficial effect on inflammation and the immune response, suggesting a possible clinical benefit. Clinical studies of FOC-IVLEs have reported mixed results. The aim of this review is to present findings from recent randomized controlled clinical trials and other quality clinical studies investigating the effects of administering intravenous fish oil alone or as part of a multilipid emulsion and to examine the quality of these studies in an objective, evidence-based manner.Methods: Studies comparing FOC-IVLEs with other IVLEs in adults were included. Thirty-four clinical studies were evaluated: 19 investigated levels of inflammatory and immune markers as an endpoint; 13 investigated rates of infection or sepsis; 3 investigated clinical outcomes in septic patients; and 29 investigated general clinical outcomes.Results: There was conflicting evidence for a beneficial effect of fish oil on levels of inflammatory and immune markers and some evidence that fish oil decreased the rate of postoperative atrial fibrillation. Studies generally reported few statistical differences in clinical outcomes and rates of infection and sepsis with FOC-IVLEs as compared with other IVLEs. The quality of reporting was generally poor, and the presented evidence for comparisons between FOC-IVLEs and other IVLEs was inconclusive or weak.Conclusions: There is very little high-quality evidence that FOC-IVLEs have a more beneficial effect than other IVLEs on clinical outcomes in adult patients. [ABSTRACT FROM AUTHOR]

Highlights • GPR120 is required for fish oil-mediated hepatic protection from parenteral nutrition-induced liver injury. • PPARγ and its downstream effectors CD36 and SCD1 are dysregulated by a parenteral nutrition diet and normalized by intravenous fish oil in a GPR120-dependent fashion. • GPR120-mediated PPARγ signaling to CD36 and SCD1 activity may represent one pathway that contributes to the modulation of intestinal failureassociated liver disease. • GPR120, PPARγ, CD36, and SCD1 may be potential targets for small molecule-based hepatic protection strategies in intestinal failure-associated liver disease and other similar hepatic pathologies. Abstract Intravenous fish oil lipid emulsions (FOLE) can prevent parenteral nutrition (PN)-induced liver injury in murine models and reverse PN-induced cholestasis in pediatric patients. However, the mechanisms by which fish oil protects the liver are incompletely characterized. Fish oil is rich in omega-3 fatty acids, which are ligands for the G-protein coupled receptor 120 (GPR120), expressed on hepatic Kupffer cells. This study tested the hypothesis that FOLE protects the liver from PN-induced injury through GPR120 signaling. Utilizing a previously described murine model of PN-induced liver injury in which mice develop steatosis in response to an oral parenteral nutrition diet, FOLE was able to preserve normal hepatic architecture in wild type mice, but not in congenic GPR120 knockout (gpr120−/−) mice. To further characterize the requirement of intact GPR120 for FOLE-mediated hepatic protection, gene expression profiles of key regulators of fat metabolism were measured. PPARγ was identified as a gene that is up-regulated by the PN diet and normalized with the addition of FOLE in wild type, but not in gpr120−/− mice. This was confirmed at the protein expression level. A PPARγ expression array further identified CD36 and SCD1, both down-stream effectors of PPARγ, to be up-regulated in PN-fed wild type mice yet normalized upon FOLE administration in wild type but not in gpr120−/− mice. Together, these results suggest that FOLE protects the liver, in part, through activation of GPR120 and the downstream effectors PPARγ and CD36. Identification of key genetic determinants of FOLE-mediated hepatic protection may provide targets for small molecule-based hepatic protection strategies. [ABSTRACT FROM AUTHOR]

Background: There are many advantages of a SMOF emulsion (SMOF-lipid), such as liver-protective properties and anti-inflammatory effects. The objective of this study was to compare the clinical outcomes of SMOF-lipid with medium-chain triglycerides (MCT) /long-chain triglycerides (LCT) in infants after intestinal surgery.Methods: This was a prospective, randomized study. Neonates receiving intravenous nutrient solution, including lipid emulsion after gastrointestinal surgery, were included in this study. The patients were randomly assigned to the SMOF-lipid or MCT/LCT groups. Infants who received intravenous lipid emulsion continuously for > 2 weeks were considered to have completed the study. Differences in weight gain, nutrition indices, alanine transaminase (ALT), aspartate transaminase (AST), and direct bilirubin (DB), and inflammation cytokine markers (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) were measured.Results: The final sample included 160 infants. One hundred fourteen infants received intravenous SMOF-lipid (74) or MCT/LCT (86) > 2 weeks and 46 infants received intravenous SMOF-lipid (22) or MCT/LCT (24) > 4 weeks. There were no significant differences in weight gain, nutrition indices, inflammation cytokine markers, and sepsis between the groups at the end of 2 and 4 weeks; however, in the SMOF group, the ALT, AST, and DB levels were significantly lower than the MCT/LCT group at the end of 4 weeks.Conclusion: The mixture and balanced emulsion of SMOF-lipid was well-tolerated in infants who have undergone gastrointestinal surgery, and liver-protective properties were demonstrated following long-term venous nutrition, especially > 4 weeks. [ABSTRACT FROM AUTHOR]

Background: The compliance of lipid admixtures to physical emulsion stability parameters is extremely important to ensure the safety of patients. For example, admixtures containing a percentage of fat globules larger than 5 μm in diameter (concept known as PFAT5) of more than 0.05% might produce toxic effects in lung and liver. This concern is mainly based on a limited number of animal studies investigating admixtures with high PFAT5 levels resulting from 48 h of admixture storage. However, all effects observed in these studies might as well be attributed to chemical instability like lipid oxidation, which was not analysed and therefore could not be excluded. Aims: This study aims at investigating the correlation of high levels of PFAT5 in lipid emulsion admixtures with lipid oxidation parameters under different storage conditions. Methods: We studied the physical (PFAT5 value) as well as the chemical (pH, primary and secondary oxidation parameters) stability of an admixture of a lipid emulsion and an amino acid solution after up to 48 h following different storage conditions (exposure to oxygen, exposure to artificial light). Results: High levels of PFAT5 were only observed after exposure of the admixture to oxygen. Additional exposure to artificial light led to a parallel increase in the primary and secondary oxidation parameters, while the pH was unchanged. Conclusions: The admixtures investigated in the former animal studies were obviously both physically and chemically unstable and all effects observed in the studies could just as well be caused by chemical instability, namely the administration of lipid peroxides with the admixture.

Background: Essential fatty acid (EFA) status may be compromised during the intestinal failure (IF) rehabilitation. Parenteral lipid restriction is used to treat intestinal failure associated liver disease (IFALD), while the enteral fatty acid (FA) absorption remains limited. We analyzed the FA status among pediatric IF and intestinal insufficiency patients.Methods: We evaluated 49 patients aged 0-18 years attending our nationwide IF referral center. Their serum FA fractions were determined and examined against previous nutrition, parenteral lipid emulsion, and intestinal anatomy data. The patients were divided into 3 subgroups according to their dependence on parenteral nutrition (PN): full enteral (EN) (n = 33), supplemental PN (n = 14) or predominantly PN (n = 20). Trien:tetraen ratio (TTR) ≥0.2 was considered diagnostic for essential fatty acid deficiency (EFAD) and increased risk was suspected if TTR exceeded 0.1.Results: We identified 8 (16%) patients with elevated TTR ≥0.1; in 3 of them the ratio exceeded 0.2. Five of these children belonged to supplemental PN group. This group carried the highest incidence of elevated TTR (P = 0.0016), with median TTR at 0.06 (interquartile range 0.03-0.09) and two-thirds of the analyzed TTR ≥0.5. Increased EFAD risk was associated with young age (P = 0.0291), current PN with low parenteral lipid content (P = 0.0003), and short remaining small bowel (P = 0.0013).Conclusions: IF children with supplemental PN carry the highest overall risk for EFAD. Young age, current PN, and short remaining small bowel also increase the risk for EFAD. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX) solution is among the most widely-used parenteral formulations used in advanced breast cancer therapy. However, severe side effects have been observed due to the use of ethanol and polysorbate 80. Herein, a novel DTX-based prodrug, docetaxel-linoleic acid conjugate (DTX-LA) was successfully synthesized. The high lipid solubility of DTX and DTX-LA resulted in a tendency for them to become entrapped in the oil core of the emulsions. As anticipated, nano-sized, sterically stabilized oil-in-water lipid emulsions (LMs) of DTX-LA LMs and DTX LMs were successfully constructed. Unlike DTX solution, LMs exhibited high colloidal stability and sustained-release behavior, having a narrow size distribution that was ∼220 nm in diameter. Compared with DTX LMs, DTX-LA LMs had a greater drug-loading capacity. Although the cytotoxicity of DTX-LA LMs was reduced in comparison with DTX solution, the pharmacokinetic study demonstrated increased bioavailability (p < 0.001) and half-life (p < 0.01). Finally, DTX-LA LMs displayed significant antitumor efficacy with reduced side effects in a 4T1 breast cancer xenograft model. Thus, the novel lipid emulsion-based docetaxel prodrug delivery system may be a promising strategy for improving intravenous administration for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The purpose of the study was to design a novel octa-arginine (R8) modified lipid emulsion (LE) system for the ocular delivery of the lipophilic drug disulfiram (DSF). The influence of the particle size of the lipid emulsions and the presence of R8 on corneal permeation was studied. DSF-loaded lipid emulsions with different particle sizes (DSF-LE1, DSF-LE2, DSF-LE3) and DSF-loaded lipid emulsions modified with R8 (DSF-LE1-R8 and DSF-LE2-R8) were prepared. The Zeta potential of the lipid emulsions was changed from negative to a positive value after modification of R8. The mucoadhesion of different preparations was investigated, and DSF-LE1-R8 was found to produce the strongest mucoadhesion. The in vitro corneal penetration study and in vivo ocular distribution study showed that the R8 modified lipid emulsion (DSF-LE1-R8) with a nano particle size, exhibited the highest permeability and the largest amount of DDC distributed in ocular issues. Coumarin-6 labelled LE1-R8 displayed more homogeneous fluorescence with the deeper penetration into the cornea compared with other preparations at various times. Confocal laser scanning microscopy showed that, in addition to paracellular routes, LE-R8 could also transport across the corneal epithelium by transcellular routes as a result of increased uptake due to the R8 modification. Furthermore, the anti-cataract effect was evaluated and it was found that DSF-LE1-R8 exhibited a marked anti-cataract effect. Therefore, the lipid emulsions with nano-sized particles and modification of R8 were proposed as a potential ocular delivery system to improve the corneal penetration and ocular delivery of DSF. [ABSTRACT FROM AUTHOR]

Background: Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported.Materials and Methods: We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions.Results: Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03).Conclusion: Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage. [ABSTRACT FROM AUTHOR]

Systemic local anesthetic (LA) toxicity is the most fatal complication of peripheral nerve block techniques. LA was accidentally applied to intravenous or exceeding maximum dose of LA is the most frequent causes of systemic LA toxicity. In recent years, use of intravenous lipid emulsions in cases that have not responded to standard resuscitation applications have been reported in systemic LA toxicity. Our aim is to report systemic LA toxicity which was treated with intravenous lipid emulsion infusion. [ABSTRACT FROM AUTHOR]