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OBJECTIVE: To describe the incidence and to analyze risk factors associated with cholestasis in neonates with gastroschisis. METHODS: This is a retrospective cohort study in a tertiary single center analyzing 181 newborns with gastroschisis between 2009 and 2020. The following risk factors associated with cholestasis were analyzed: gestational age, birth weight, type of gastroschisis, silo closure or immediate closure, days of parenteral nutrition, type of lipid emulsion, days of fasting, days to reach a full diet, days with central venous catheter, presence of infections, and outcomes. RESULTS: Among the 176 patients evaluated, 41 (23.3%) evolved with cholestasis. In the univariate analysis, low birth weight (p=0.023), prematurity (p<0.001), lipid emulsion with medium-chain triglycerides and long-chain triglycerides (p=0.001) and death (p<0.001) were associated with cholestasis. In the multivariate analysis, patients who received lipid emulsion with fish oil instead of medium chain triglycerides/long chain triglycerides (MCT/LCT) emulsion had a lower risk of cholestasis. CONCLUSIONS: Our study shows that lipid emulsion with fish oil is associated with a lower risk of cholestasis in neonates with gastroschisis. However, this is a retrospective study and a prospective study should be performed to confirm the results.
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Colestase , Gastrosquise , Humanos , Recém-Nascido , Peso ao Nascer , Estudos Retrospectivos , Emulsões , Gastrosquise/epidemiologia , Gastrosquise/induzido quimicamente , Gastrosquise/complicações , Estudos Prospectivos , Óleo de Soja/efeitos adversos , Óleos de Peixe , Colestase/etiologia , Colestase/induzido quimicamente , TriglicerídeosRESUMO
Parenteral nutrition, received by many patients with intestinal failure, can induce hepatobiliary complications, which is termed as parenteral nutrition-associated liver disease (PNALD). The spectrum of PNALD ranges from cholestasis and steatosis to fibrosis and cirrhosis. Although many factors contribute to the pathogenesis of PNALD, the underlying mechanisms remain unclear. In this study, we performed targeted metabolomics to characterize the metabolomic profile in neonatal piglets receiving total parenteral nutrition (TPN) or enteral nutrition (EN) for 1 or 2 weeks. Overall, the metabolomic signature of TPN groups differed from EN groups at both time points. Among the 20 acylcarnitines identified, a majority of them were significantly reduced in TPN groups. KEGG pathway analysis showed that phenylalanine metabolism-associated pathways were dysregulated accompanied by more progressive liver steatosis associated with TPN. Next, we evaluated phenylalanine catabolism and its association with fatty acid oxidation in piglets and rats with PNALD. We showed that the hepatic expression of phenylalanine-degrading enzyme phenylalanine hydroxylase (PAH) was reduced and systemic phenylalanine levels were increased in both animal models of PNALD. Moreover, carnitine palmitoyltransferase 1A, a central regulator of fatty acid oxidation, was downregulated and its expression was negatively correlated with phenylalanine levels in TPN-fed animals. To explore the effects of phenylalanine accumulation on lipid metabolism, we treated HepG2 cells with phenylalanine co-cultured with sodium palmitate or soybean oil emulsion to induce lipid accumulation. We found that phenylalanine treatment exacerbated lipid accumulation by inhibiting fatty acid oxidation without affecting fatty acid synthesis. In summary, our findings establish a pathogenic role of increased phenylalanine levels in driving liver steatosis, linking dysregulation of phenylalanine catabolism with lipid accumulation in the context of PNALD.
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Fígado Gorduroso , Hepatopatias , Animais , Suínos , Ratos , Animais Recém-Nascidos , Nutrição Parenteral Total/efeitos adversos , Fígado/metabolismo , Hepatopatias/patologia , Fígado Gorduroso/metabolismo , Óleo de Soja/efeitos adversos , Óleo de Soja/metabolismo , Ácido Palmítico/farmacologia , MetabolômicaRESUMO
OBJECTIVE: This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. METHODS: This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. RESULTS: No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). CONCLUSIONS: The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.
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Colestase , Recém-Nascido Prematuro , Recém-Nascido , Humanos , Estudos Prospectivos , Emulsões Gordurosas Intravenosas/efeitos adversos , Óleo de Soja/efeitos adversos , Azeite de Oliva , Óleos de Peixe , Colestase/etiologia , Triglicerídeos , Bilirrubina , Recém-Nascido de muito Baixo PesoRESUMO
OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.
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Colestase , Enteropatias , Insuficiência Intestinal , Hepatopatias , Falência Hepática , Recém-Nascido , Lactente , Humanos , Criança , Óleo de Soja/efeitos adversos , Hepatopatias/complicações , Enteropatias/etiologia , Enteropatias/terapia , Falência Hepática/complicações , Emulsões Gordurosas Intravenosas/efeitos adversos , Bilirrubina , Óleos de PeixeRESUMO
BACKGROUND AND OBJECTIVES: Conventional soybean oil-based intravenous lipid emulsions (SO-ILEs) have high polyunsaturated fatty acid (PUFA) contents and phytosterols that may have adverse effects in preterm infants. Recently, the multi-oil-based intravenous lipid emulsion (MO-ILE), SMOFlipid, has been widely utilized in the neonatal intensive care unit (NICU), but significant benefits over SO-ILEs in low gestational age neonates have yet to be demonstrated. This study was performed to compare the effects of the SO-ILE, Intralipid, and the MO-ILE, SMOFlipid, on neonatal health outcomes in preterm infants. METHODS AND STUDY DESIGN: We performed a retrospective review of preterm infants born at gestational week (GW) <32 receiving parenteral nutrition for longer durations (≥14 d) in the NICU between 2016 and 2021. The primary aim of this study was to investigate differences in morbidity between preterm infants receiving SMOFlipid and Intralipid. RESULTS: A total of 262 preterm infants were included in the analysis, with 126 receiving SMOFlipid and 136 receiving Intralipid. The SMOFlipid group had lower rates of ROP (23.8% vs 37.5%, respectively; p=0.017), although the rate of ROP was not different in multivariate regression analysis. The length of hospi-tal stay was significantly shorter in the SMOFlipid than SO-ILE group (median [IQR]=64.8 [37] vs 72.5 [49] days; p<0.001). CONCLUSIONS: The use of SMOFlipid as the lipid emulsion was associated with higher clinical efficacy than SO-ILE in preterm infants.
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Recém-Nascido Prematuro , Óleo de Soja , Lactente , Recém-Nascido , Humanos , Óleo de Soja/efeitos adversos , Óleos de Peixe , Emulsões Gordurosas Intravenosas , Nutrição Parenteral/métodos , Azeite de Oliva , Ácidos Graxos Insaturados , TriglicerídeosRESUMO
INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. METHODS: We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. RESULTS: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. CONCLUSION: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.
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Emulsões Gordurosas Intravenosas , Óleo de Soja , Humanos , Óleo de Soja/efeitos adversos , Emulsões Gordurosas Intravenosas/farmacologia , Emulsões Gordurosas Intravenosas/uso terapêutico , Estado Terminal/terapia , Estudos Retrospectivos , Azeite de Oliva , Óleos de Plantas/efeitos adversos , Nutrição Parenteral/efeitos adversos , Óleos de Peixe/farmacologia , Óleos de Peixe/uso terapêutico , Bilirrubina , HospitaisRESUMO
As a food contaminant, oxidized oil or lipid oxidative products have been proven to exert toxicological effects on the growth and development of animals and humans. Research shows that maternal oxidative stress damage might transmit to another generation by epigenetic modulation. However, current evidence is still not clear on the mechanism of the effects of dietary oxidized oil during pregnancy on the two generations. This study employed a rat model fed with oxidized soybean oil (OSO) during pregnancy and lactation to explore the effects of the oxidative degree (0, 200, 400, and 800 mequiv of O2/kg) on the placental RNA methylation and DNA methylation in offspring jejunum. The results showed that following the ingestion of OSO, the placental genes of different m6A methylation were significantly enriched to nutrient metabolic processes and hormone activity. In addition, the intestine in offspring hypofunctioned observably, such as reducing the height of villi and the level of anti-inflammatory cytokine. Furthermore, maternal intake of OSO during pregnancy can damage the intestinal barrier function of offspring by inhibiting the proliferation and differentiation of intestinal epithelial cells and reducing the activity of intestinal DNA methyltransferase. In conclusion, this study reinforces the assertion that maternal OSO consumption during gestation and lactation negatively affects the placental health and intestinal development of suckling pups.
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Gorduras Insaturadas na Dieta , Óleo de Soja , Animais , Metilação de DNA , Feminino , Intestinos , Lactação , Placenta , Gravidez , Ratos , Óleo de Soja/efeitos adversosRESUMO
WHAT IS KNOWN AND OBJECTIVES: Errors involving the delivery of IVFE containing soybean oil have known significant complications, including fat overload syndrome. However, little is known regarding the risks of fat overload syndrome with other types of lipid emulsions. CASE SUMMARY: We describe a medication administration error that resulted in rapid fish oil-base lipid emulsion (Omegaven) infusion in a five-month-old infant with parenteral nutrition associated liver disease (PNALD). The medication administration error resulted in bolus infusion of Omegaven over 12 min (5 g/kg/h) instead of 12 h (0.083 g/kg/h). WHAT IS NEW AND CONCLUSION: No adverse reactions were notes because of the rapid infusion, supporting conclusion that rapid infusion of fish oil will not result in fat overload syndrome.
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Emulsões Gordurosas Intravenosas , Hepatopatias , Emulsões Gordurosas Intravenosas/efeitos adversos , Óleos de Peixe/efeitos adversos , Humanos , Nutrição Parenteral/efeitos adversos , Nutrição Parenteral/métodos , Óleo de Soja/efeitos adversosRESUMO
High-fat diets are linked to obesity, contributing to the alterations in inflammatory signaling pathways, which is associated with cognitive function. We aim to investigate the mechanisms by which various different types of dietary fatty acids affecting cognitive function in obese mice through the gut/brain axis-inflammatory signaling pathway. 8-week-old male C57BL/6 mice were fed with basal diet (control group), lard high-fat diet (containing long-chain saturated fatty acid (LCSFA group)), coconut oil high-fat diet (containing medium-chain saturated fatty acid (MCSFA group)), linseed oil high-fat diet (containing n-3 polyunsaturated fatty acid (n-3 PUFA group)), soybean oil high-fat diet (containing n-6 polyunsaturated fatty acid (n-6 PUFA group)), olive oil high-fat diet (containing monounsaturated fatty acid (MUFA group)) and 8% hydrogenated soybean oil high-fat diet (containing trans fatty acid (TFA group)) respectively for 16 weeks. Our results revealed that the mean escape latency was significantly prolonged in LCSFA group, and the latency to cross the platform location of n-6 PUFA and TFA groups were increased significantly. The differences of inflammatory markers and toll-like receptor-myeloid differentiation factor-88-nuclear factor kappa-B (TLR-MyD88-NF-κB) inflammatory signaling pathway expressions among all groups reached statistical significances. Compared to basal diet, high-fat diets enriched in LCSFA, MCSFA, n-6 PUFA, MUFA, and TFA might exert detrimental effects on cognitive function in obese mice via regulating the inflammatory markers and inflammatory signaling pathway in brain and intestine. High-fat diet enriched in n-3 PUFA might exhibit different effect on modulating inflammatory responses in different tissues and might benefit to cognitive function.
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Ácidos Graxos Ômega-3 , Óleo de Soja , Animais , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Ácidos Graxos , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Óleo de Soja/efeitos adversosRESUMO
PURPOSE OF REVIEW: Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. RECENT FINDINGS: The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. SUMMARY: Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.
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Enteropatias , Insuficiência Intestinal , Hepatopatias , Animais , Emulsões Gordurosas Intravenosas/efeitos adversos , Ácidos Graxos , Óleos de Peixe , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Enteropatias/complicações , Enteropatias/terapia , Hepatopatias/etiologia , Hepatopatias/terapia , Óleo de Soja/efeitos adversosRESUMO
OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.
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Emulsões Gordurosas Intravenosas/efeitos adversos , Óleos de Peixe/efeitos adversos , Insuficiência Intestinal/terapia , Hepatopatias/etiologia , Nutrição Parenteral/efeitos adversos , Óleo de Soja/efeitos adversos , Emulsões Gordurosas Intravenosas/uso terapêutico , Feminino , Óleos de Peixe/uso terapêutico , Humanos , Lactente , Recém-Nascido , Insuficiência Intestinal/complicações , Masculino , Nutrição Parenteral/métodos , Estudos Retrospectivos , Óleo de Soja/uso terapêutico , Resultado do TratamentoRESUMO
High levels of soybean oil (SO) in fish diets enriched with linoleic acid (LA, 18:2n-6) could induce strong inflammation. However, the molecular mechanism underlying LA-induced inflammation in the liver of large yellow croaker (Larimichthys crocea) has not been elucidated. Based on previous research, autophagy has been considered a new pathway to relieve inflammation. Therefore, the present study was performed to investigate the role of autophagy in regulating LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro. The results of the present study showed that activation of autophagy in liver or hepatocytes could significantly reduce the gene expression of proinflammatory factors, such as tumor necrosis factor α (TNFα) and interleukin 1ß (IL1ß). The results of the present study also showed that inhibition of autophagy could upregulate the gene expression of proinflammatory factors and downregulate the gene expression of anti-inflammatory factors in vivo and in vitro. Furthermore, autophagy could alleviate LA-induced inflammatory cytokine gene expression in vivo and in vitro, while inhibition of autophagy obtained the opposite results. In conclusion, our study shows that autophagy could regulate inflammation and alleviate LA-induced inflammation in the liver of large yellow croaker in vivo and in vitro for the first time, which may offer considerable benefits to the aquaculture industry and human health.
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Autofagia , Doenças dos Peixes/imunologia , Hepatite Animal/imunologia , Ácido Linoleico/efeitos adversos , Perciformes/imunologia , Ração Animal/efeitos adversos , Animais , Aquicultura , Células Cultivadas , Doenças dos Peixes/induzido quimicamente , Doenças dos Peixes/patologia , Hepatite Animal/induzido quimicamente , Hepatite Animal/patologia , Hepatócitos/imunologia , Fígado/imunologia , Fígado/patologia , Cultura Primária de Células , Óleo de Soja/efeitos adversos , Óleo de Soja/químicaRESUMO
INTRODUCTION: As an exogenous food contaminant, dietary oxidized lipid impairs growth and development, and triggers chronic diseases in humans or animals. This study explores the effects of soybean oil with different oxidative degree on the placental injury of gestational rats. METHODS AND RESULTS: Thirty-two female adult rats are randomly assigned to four groups. The control group is fed the purified diet with fresh soybean oil (FSO), and the treatment groups are fed purified diets with lipid content replaced by oxidized soybean oil (OSO) at 200, 400, and 800 mEqO2 kg-1 from conception until delivery. On day 20 of gestation, OSO decreased placental and embryonic weights as the oxidative degree increased linearly and quadratically. The expression of Bax showed a linear increase, and Bcl-2 decreased as the oxidative degree increased. The expression of Fosl1 and Esx1 is linearly and quadratically decreased in OSO-treated groups than FSO group. OSO decreased the level of IL-10 but increased expression of IL-1ß in placenta and plasma. OSO remarkably upregulates levels of Fatp1 and Glut1 and decreases expression of Snat2 and Glut3. CONCLUSION: OSO aggravates placental injury by modulating nutrient transporters and apoptosis-related genes, impedes placental growth and development, and ultimately leads to the decrease of fetal weight.
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Proteínas de Transporte/metabolismo , Exposição Materna/efeitos adversos , Placenta/efeitos dos fármacos , Óleo de Soja/efeitos adversos , Óleo de Soja/química , Sistema A de Transporte de Aminoácidos/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Citocinas/sangue , Citocinas/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Peso Fetal/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Transportador de Glucose Tipo 3/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Placenta/metabolismo , Placenta/patologia , Placentação/efeitos dos fármacos , Gravidez , Ratos Sprague-DawleyRESUMO
BACKGROUND & AIMS: Mixed oil intravenous lipid emulsion (MO ILE) that contains 30% soybean oil (SO), 30% medium chain triglycerides, 25% olive oil and 15% fish oil can benefit hospitalized patients receiving parenteral nutrition (PN) but there are very few studies on its long-term use. Our goal was to evaluate the clinical outcomes of adults receiving home PN (HPN) with MO versus those receiving SO ILE over a 2-year period. METHOD: This is a retrospective analysis of data collected prospectively from a cohort of patients recorded in the Canadian HPN Registry over a 2-year period. HPN patients from academic programs across Canada were entered in the Registry according to a validated protocol. For this study, demographic, nutritional, laboratory and clinical data were extracted from January 1st 2015, when MO lipid emulsion became available in Canada, to July 24th 2019. Clinical data for each patient included: number of hospitalizations, number of hospitalizations related to HPN and number of hospitalization days related to HPN, over a year; incidence of line sepsis per 1000 catheter days and mortality. Data are presented as median (1st, 3rd quartile) for continuous variables and frequency (percentage) for categorical variables. Comparisons between groups were performed using two sample t-test or Wilcoxon Rank Sum tests for continuous variables and Chi-square tests or Fisher's exact tests for categorical variables. Univariate and multiple linear regressions were also carried out. Statistical significance is set at a p-value <0.05. RESULTS: A total of 120 patients were included (MO n = 68, SO n = 52). Significant differences at baseline between the two groups were a higher use of Hickman line (62.12% vs 42%, p = 0.038) and more western Canada based hospital care with MO (75% vs 42.31%, p = 0.0002). The MO group had significantly more hospitalizations (p = 0.001), more hospitalizations related to HPN (p = 0.012) and more hospitalization days related to HPN (p = 0.016) per patient per year compared to SO patients. There was no significant difference between groups for line sepsis per 1000 catheter days (MO: 0.05 (0.0, 1.0) vs SO: 0.0 (0.0, 0.22), p = 0.053) or mortality. All other variables, including biochemical variables, were similar between groups. In a multiple regression analysis, the following factors were significantly associated with a greater number of hospitalizations per patient per year: use of MO, high blood glucose from the last recorded value and having died by the end of the study period. CONCLUSION: This 2-year prospective cohort study suggests an increased risk of hospitalization in HPN patients receiving MO lipid emulsion. The long-term effect of using MO lipid emulsion in HPN patients should be further evaluated using a large randomized controlled trial. THE STUDY WAS REGISTERED IN CLINICALTRIALS.GOV: (NCT02299466).
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Gorduras na Dieta/efeitos adversos , Emulsões Gordurosas Intravenosas/efeitos adversos , Hospitalização/estatística & dados numéricos , Nutrição Parenteral no Domicílio/estatística & dados numéricos , Óleo de Soja/efeitos adversos , Adulto , Canadá , Gorduras na Dieta/administração & dosagem , Emulsões Gordurosas Intravenosas/química , Feminino , Óleos de Peixe/administração & dosagem , Gastroenteropatias/terapia , Neoplasias Gastrointestinais/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Azeite de Oliva/administração & dosagem , Nutrição Parenteral no Domicílio/métodos , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Síndrome do Intestino Curto/terapia , Óleo de Soja/administração & dosagem , Triglicerídeos/administração & dosagemRESUMO
With regards to cardiovascular health, frequent consumption of fried foods is discouraged, despite a lack of clear evidence of a direct link between eating oxidative frying oil (OFO) and cardiovascular diseases. In this study, male Sprague Dawley rats were exposed to diets containing fresh or fried soybean oil (groups C and O, respectively) from in utero to 28 weeks of age. A subset of rats in group O was supplemented with vitamin E (500 mg/kg of DL-α-tocopherol acetate; group OE) from 8 week of age onward to mitigate oxidative stress associated with OFO ingestion. Echocardiography, cardiac histology and indices associated with ATP production and calcium cycling in cardiac tissues were measured. Compared to group C, there was cardiac hypertrophy, fibrosis and diastolic dysfunction, in groups O and OE, with no differences between the latter two groups. Although cardiac mRNA levels of genes associated with mitochondrial biogenesis and function were increased, there were lower ATP concentrations and higher transcripts of uncoupling proteins in groups O and OE than in group C. In addition, decreases in phosphorylation of phospholamban and Ca2+/calmodulin-dependent protein kinase II activity, plus increased protein phosphatase 2A activity in groups O and OE, implied calcium cycling required for cardiac function was disrupted by OFO consumption. We concluded that long-term OFO exposure resulted in cardiac hypertrophy, fibrosis and diastolic dysfunction that was not mitigated by vitamin E supplementation. Underlying mechanisms were partly attributed to inefficient energy production via uncoupled phosphorylation and disrupted calcium cycling.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Cálcio/metabolismo , Cardiomegalia/etiologia , Óleo de Soja/efeitos adversos , Vitamina E/farmacologia , Animais , Antioxidantes/farmacologia , Proteínas de Ligação ao Cálcio/metabolismo , Culinária/métodos , Dieta/métodos , Feminino , Fibrose/etiologia , Masculino , Miocárdio/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Óleo de Soja/farmacologiaRESUMO
Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.
Assuntos
Ácidos Graxos Insaturados/administração & dosagem , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estresse Oxidativo/fisiologia , Animais , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Interleucina-6/metabolismo , Fígado/metabolismo , Masculino , Peroxidase/metabolismo , Ratos , Ratos Wistar , Componente Amiloide P Sérico/metabolismo , Óleo de Soja/efeitos adversosAssuntos
Bilirrubina/sangue , Óleos de Peixe/efeitos adversos , Lipídeos/efeitos adversos , Azeite de Oliva/efeitos adversos , Nascimento Prematuro , Óleo de Soja/efeitos adversos , Triglicerídeos/efeitos adversos , Feminino , Óleos de Peixe/metabolismo , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/tratamento farmacológico , Recém-Nascido , Azeite de Oliva/metabolismo , Nascimento Prematuro/sangue , Óleo de Soja/metabolismo , Triglicerídeos/metabolismoRESUMO
PURPOSE: Results of a study comparing the safety and efficacy outcomes with use of a soybean oil-based injectable lipid emulsion (SO-ILE) vs a 4-oil alternative product in a neonatal population are presented. METHODS: In an institutional review board-approved, multicenter retrospective review, the medical records of 328 patients who were born at a gestational age of ≤34 weeks, had a birth weight of 500 to 2,000 g, were admitted to one of 2 neonatal intensive care units (NICUs) within a large health system, and received at least 7 days of a parenteral nutrition containing either lipid emulsion product were reviewed: 151 (46%) had received SO-ILE and 177 (54%) had received SMOFlipid (Fresenius Kabi). The primary outcome of the study was a composite of development of cholestasis and development of hypertriglyceridemia. Secondary outcomes included total duration of cholestasis treatment with ursodiol and change in body weight from initiation to completion of lipid emulsion treatment. RESULTS: The primary outcome of development of cholestasis or hypertriglyceridemia occurred in 14.6% of patients in the SO-ILE group and 18.1% of patients in the SMOFlipid group (P = 0.393). There were no statistically significant differences between the groups in total days of ursodiol treatment or average body weight change during the course of lipid emulsion treatment. CONCLUSION: In preterm neonates weighing 500 to 2,000 g, use of SMOFlipid did not significantly reduce the incidence of cholestasis or hypertriglyceridemia relative to the incidence with use of SO-ILE. Further research to validate these results is needed.
Assuntos
Emulsões Gordurosas Intravenosas , Óleo de Soja , Emulsões Gordurosas Intravenosas/efeitos adversos , Óleos de Peixe , Humanos , Lactente , Recém-Nascido , Azeite de Oliva , Estudos Retrospectivos , Óleo de Soja/efeitos adversos , TriglicerídeosRESUMO
BACKGROUND: Neonates requiring long-term parenteral nutrition (PN) are at risk for developing intestinal failure-associated liver disease (IFALD). The purpose of this study was to compare the incidence and severity of IFALD in a highly surgical neonatal population receiving mixed oil-based lipid emulsions (MOLEs) vs soybean oil-based lipid emulsions (SOLEs) for long-term PN. METHODS: This retrospective cohort study evaluated patients admitted to a neonatal intensive care nursery that received PN for ≥14 days. Patients were separated into 2 cohorts; those who received SOLE and those who received MOLE. The primary outcome of this study was the occurrence of IFALD. Secondary outcomes included time to IFALD, peak bilirubin level during therapy, incidence of hypertriglyceridemia, bronchopulmonary dysplasia, and retinopathy of prematurity. RESULTS: A total of 107 patients were included in the study, IFALD occurred in 44.8% of patients receiving SOLE compared with 30% of patients receiving MOLE (relative risk, 0.67; 95% CI, 0.39-1.15). In the multivariable analysis, adjusting for the known confounders (prematurity, necrotizing enterocolitis, presence of ostomy, and duration of PN and lipids), the type of lipids was not a significant predictor for development of IFALD. Duration of PN and duration of lipids were determined to be significant risk factors for IFALD, regardless of type of lipid emulsion (odds ratio, 1.03; 95% CI, 1.01-1.05). CONCLUSIONS: Use of MOLE resulted in no significant difference in the outcomes studied when compared with SOLE. Duration of PN and duration of lipids were significant risk factors for development of IFALD.
Assuntos
Enteropatias , Hepatopatias , Emulsões , Emulsões Gordurosas Intravenosas/efeitos adversos , Óleos de Peixe , Humanos , Incidência , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Enteropatias/epidemiologia , Enteropatias/etiologia , Enteropatias/terapia , Estudos Retrospectivos , Óleo de Soja/efeitos adversosRESUMO
OBJECTIVE: To compare the aspartate aminotransferase to platelet ratio index, liver transplantation, and mortality rates between children with intestinal failure-associated liver disease who received fish oil lipid emulsion (FOLE) or soybean oil intravenous lipid emulsion (SOLE). STUDY DESIGN: In this multicenter integrated analysis, FOLE recipients (1 g/kg/d) (n = 189) were compared with historical controls administered SOLE (≤3 g/kg/d) (n = 73). RESULTS: Compared with SOLE, FOLE recipients had a higher direct bilirubin level at baseline (5.8 mg/dL vs 3.0 mg/dL; P < .0001). Among FOLE recipients, 65% experienced cholestasis resolution vs 16% of SOLE recipients (P < .0001). The aspartate aminotransferase to platelet ratio index scores improved in FOLE recipients (1.235 vs 0.810 and 0.758, P < .02) but worsened in SOLE recipients (0.540 vs 2.564 and 2.098; P ≤ .0003) when baseline scores were compared with cholestasis resolution and end of study, respectively. Liver transplantation was reduced in FOLE vs SOLE (4% vs 12%; P = .0245). The probability of liver transplantation in relation to baseline direct or conjugated bilirubin (DB) was lower in FOLE vs SOLE recipients (1% vs 9% at DB of 2 mg/dL; 8% vs 35% at DB of 12.87 mg/dL; P = .0022 for both). Death rates were similar (FOLE vs SOLE: 10% vs 14% at DB of 2 mg/dL; 17% vs 23% at a DB of 12.87 mg/dL; P = .36 for both). CONCLUSIONS: FOLE recipients experienced a higher rate of cholestasis resolution, lower aspartate aminotransferase to platelet ratio index, and fewer liver transplants compared with SOLE. This study demonstrates that FOLE may be the preferred parenteral lipid emulsion in children with intestinal failure-associated liver disease when DB reaches 2 mg/dL. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00910104 and NCT00738101.