Administration Of Emulsion Research Articles

Parenteral lipid nutrition in congenital gastrointestinal malformation operated cases

Background: Congenital gastrointestinal malformation (CGIM) cases require immediate surgical correction after birth and proper nutrition to meet energy demands. Among the macronutrients, lipids are considered the major energy source, playing a vital role in parenteral nutrition. However, the time of their initiation remains unclear. We compared the data of CGIM cases where lipids were given from the first post-surgical day to those where parenteral lipids were initiated on the second or third day of surgery and then reevaluated them on the seventh day of parenteral nutrition.Methods: We collected the data of patients who had undergone surgical correction for CGIM and were kept on parenteral nutrition including lipids from day 1 of surgery labeling them as group 1. Group 2 comprised of neonates having lipid parenteral nutrition started from day 2 or 3 of surgery. Both groups were reevaluated on the 7th day of parenteral nutrition. Statistical analysis was performed.Results: Group 1 had higher total bilirubin (TB) statistically significant (p-value=0.0299), as well as lower lipase (p-value=0.0286), and lower total lipids (p-value=0.0365). The values were lower of triglycerides (p-value=0.0365), and total lipids (p-value=0.0365), on day 1. Comparing both groups, all biochemical parameters were found to be statistically significant.Conclusion: Lipid deficiency and overload should be carefully evaluated, especially in neonates having undergone recent surgical interventions, which increase their nutritional demands. No adverse effects were seen in our study related to parenteral lipid emulsion administration in post-surgical congenital gastrointestinal malformation cases. Early initiation of parenteral lipid regimens can provide better outcomes.Keywords: Congenital gastrointestinal malformations; Intravenous lipid emulsions; Parenteral nutrition; Gestational age; Milk formula

A novel method in myocardial injury risk stratification using intravenous fat emulsion as sole rapid preparation for unfasted patients to suppress myocardial 18F-fluorodeoxyglucose uptake for optimal cardiac PET imaging: a proof-of-concept randomized-crossover trial.

Optimal imaging of ischemic or inflammed myocardium via 18F-FDG PET imaging requires suppression of background carbohydrate metabolism in normal myocardium. Sole administration of intravenous lipid emulsion has not previously been used to rapidly prepare unfasted patients, such as in emergent clinical situations. In this proof-of-concept pilot, we posited that intravenous fat emulsion suppresses physiological metabolic uptake of in non-ischemic, non-inflammatory myocardium in unprepared and unfasted setting for enhanced cardiac positron emission tomography (PET) imaging. We conducted an ethics-approved, single-blind, prospective randomized crossover trial of 10 healthy volunteers from January 2020 to June 2021. Participants were unfasted and rendered hyperglycemic before being administered either high dose intravenous lipid emulsion-1.5 ml kg of 20% lipid emulsion, followed by 15 ml/kg/hr for 30mins-or saline prior to 18F-FDG injection and subsequent cardiac PET imaging. Assessors undertook image analysis for maximum standard uptake value (SUVmax), minimum standard uptake value (SUVmin) and qualitative assessment, and groups were compared using univariate analysis. The study population age was 44.5 years [IQR 32.5-56.5], with 50% male and a median BMI of 22.75 [IQR 25.0-28.5] kg/m2. The study was feasible and there were no adverse side effects from the interventions. In these participants with normal myocardium, 18F-FDG uptake was reduced by intravenous lipid emulsion as assessed by SUVmax and qualitative assessment (p = 0.042, r = 0.454 and p = 0.009, r = -0.581, respectively). Intravenous lipid emulsion suppresses background metabolic uptake of 18F-FDG even in unprepared and unfasted patients. Our findings prove and expand the possible applications for cardiac 18F-FDG PET in various settings, including in emergent settings as a means of rapid preparation in place of current more time-consuming standard protocols, allowing time-critical management to be effected.

Intravenous lipid emulsions designed to meet preterm infant requirements increase plasma and tissue levels of docosahexaenoic acid and arachidonic acid in mice

Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity. Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days. Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2±0.3 vs. 19.3±0.3%, P=1.00) and ARA (10.4±0.2 vs. 9.9±0.2% ARA, P=0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments. Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration.

Potential Use of Common Administration of Emulsion for Parenteral Nutrition and Vinpocetine: Compatibility Study and Prospect.

Vinpocetine (VP) is distributed after oral and intravenous administration, and its uptake in the thalamus, basal ganglia, and visual cortex. Due to poor bioavailability (~7%) and marked first-pass effect (~75%), including a short half-life (2-3 h), oral administration of VP is limited. It requires frequent administration of the drug to obtain a therapeutic effect. Attempts to overcome these difficulties include the use of new drug delivery systems and/or alternative routes of drug administration. One possibility is the common administration of lipid emulsion and drug using the same catheter. However, this procedure is not recommended due to potential interaction and lack of safety data. For this purpose, we checked the compatibility of VP solutions with eight commercially available parenteral nutrition admixtures, i.e., Lipoflex special, Omegaflex special, Lipoflex peri, Omegaflex peri, Kabiven, SmofKabiven, Kabiven Peripheral, and Olimel Peri N4E. Coadministration is only possible if the stability of the drug and the lipid emulsion is confirmed. The available data are scarce and only concern the incompatibility of VP with ibuprofen. Compatibility tests were carried out in simulated administration through a Y-site connector using clinical flow rates. The stability of the drug and lipid emulsion was assessed by visual inspection and measurement of pH, osmolality, particle size as mean droplet diameter (MDD) and percentage of lipids residing in globules larger than 5 µm (PFAT5), zeta potential, polydispersity index, and lipid-free parenteral nutrition admixture(PNA) turbidity. The results of the compatibility of VP with eight commercial PN admixtures showed that all lipid emulsions show different signs of destabilization. In the studied samples, particles larger than 1000 nm, a significant increase in MDD, zeta potential, and loss of homogeneity visible as an increase in the polydispersity index were observed. Most of the samples had PFAT5 above the USP limit (0.05%). Taking into account the obtained data, VP should not be administered with the studied lipid emulsions for parenteral nutrition.

Safety Profile of Lipid Emulsion in Clinical Practice: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System

Introduction: Lipid emulsion preparations, known for their clinical utility, are associated with various adverse events related to lipid metabolism. In this study, we analyzed the safety profile of lipid emulsions in clinical practice, using a real-world database. Methods: The US Food and Drug Administration Adverse Event Reporting System database was used to retrieve adverse events associated with lipid emulsion use. The risk of adverse events was evaluated based on the reported odds ratio and time-to-onset analysis. Results: A total of 4,430 relevant adverse event reports were identified. Hepatic dysfunction tended to occur in the early stages after administration, regardless of the lipid emulsion type. The incidence of hepatic dysfunction varies depending on the triglyceride content of the administered lipid emulsion. Infection tended to occur in the early stages of lipid emulsion administration; however, the incidence did not significantly differ depending on triglyceride content. Conclusion: Our study revealed adverse lipid emulsion events, indicating the need for comprehensive safety management, particularly in the early stages, for clinical use. Particularly, patients receiving parenteral nutrition, irrespective of lipid emulsion administration, necessitate thorough monitoring of liver function and triglyceride levels and reassessment of infusion rates.

Clinical effects and adverse effects of intravenous lipid emulsion treatment in dogs and cats with suspected poisoning.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.

Lipidomics study of Liujunzi decoction in hyperlipidemia rats with spleen deficiency based on UPLC-Q-TOF/MS

Hyperlipidemia refers to the abnormal levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) in peripheral blood circulation. It is a predominant risk factor underlying cardiovascular and cerebrovascular diseases, including coronary heart disease and atherosclerosis. Furthermore, it is also one of the most prevalent chronic diseases globally. Liujunzi Decoction is the basic prescription for the treatment of spleen and stomach diseases. It can tonify the spleen and qi, remove dampness, and reduce turbidity. Moreover, it is also clinically used for the treatment of spleen deficiency hyperlipidemia. However, its metabolites and therapeutic effect on spleen deficiency hyperlipidemia have not been comprehensively determined in vitro and in vivo. This study established a rat model of spleen deficiency hyperlipidemia by inducing starvation and satiety disorders, exhaustion swimming, and intragastric administration of the fat emulsion. To identify related metabolite changes and serum lipid composition, UPLC-Q-TOF-MS, PCA, and OPLS-DA lipidological methods were performed. The results demonstrated significant changes in rat's signs during the modeling process, which were consistent with the criteria for the syndrome differentiation of spleen deficiency in traditional Chinese medicine. Furthermore, this study identified 100 potential biomarkers in rat serum, of which 52 were associated with lipid synthesis, such as LPC, PC, PI, PE, PA, Cer, SM, etc. The pathways involved were glycerol phospholipid, sphingomyelin, and glycerol ester metabolisms. After the Liujunzi decoction intervention, 56 potential biomarkers were observed in the high-dose group, alleviating the metabolic spectrum imbalance by reducing metabolite levels. In addition, metabolic pathway disturbances were markedly improved. This study provides references for future studies on Liujunzi decoction and furnishes essential data for assessing the relationships between chemical constituents and pharmacological activities of Liujunzi decoction.

The Lipid Intensive Drug Therapy for Sepsis Phase II Pilot Clinical Trial.

Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. Emergency department or ICU of an academic medical center. Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cholesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr - enrollment) between groups. Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL ( sd 20) for lipid emulsion patients, and 2 mg/dL ( sd 18) for control patients ( p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients ( p = 0.46). Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours.

Chylopericardium following esophagectomy: a case report and systematic review

BackgroundChylopericardium is a rare condition characterized by the accumulation of chyle in the pericardial space. It is most commonly caused by thoracic duct injury. Chylopericardium following esophagectomy is extremely rare but can cause life-threatening complications. This report presents a case of chylopericardium post-esophagectomy, resulting in cardiac tamponade and cardiac arrest. A systematic literature review was also conducted to facilitate the understanding of this rare condition.Case presentationA 41-year-old male was admitted to our hospital with intermediate to highly differentiated squamous cell carcinoma of the mid-thoracic esophagus (clinical T4NxM0). He underwent thoracoscopic-laparoscopic esophagectomy with cervical anastomosis. On postoperative day 1, patient had a cardiac arrest secondary to cardiac tamponade, requiring emergency ultrasound-guided drainage. The drained fluid was initially serous but became chylous after the administration of enteral nutritional emulsion. As a result of significant daily pericardial drainage, patient subsequently underwent thoracic duct ligation. The amount of drainage was substantially reduced post-thoracic duct ligation. Over a period of 2 years and 7 months, patient recovered well and tolerated full oral diet. A comprehensive literature review was conducted and 4 reported cases were identified. Among these cases, three patients developed pericardial tamponade secondary to chylopericardium post-esophagectomy.ConclusionChylopericardium is a rare but serious complication post-esophagectomy. Prompt echocardiography and thorough pericardial fluid analysis are crucial for diagnosis. Thoracic duct ligation has been shown to be an effective management approach for this condition.

Impact of lipid emulsions in parenteral nutrition on platelets: a literature review.

Lipid emulsions are essential components of parenteral nutrition solutions that provide energy and essential fatty acids. The complexity of the formulations of lipid emulsions may lead to adverse outcomes such as platelet reactivity and changes in platelet aggregation and related coagulation. Platelets are responsible for haemostasis; they activate and demonstrate morphological changes upon extracellular factors to maintain blood fluidity and vascular integrity. Although parenteral nutrition lipid emulsions are generally found safe with regard to modulation of platelet activity, studies are still accumulating. Thus, this review aims to investigate platelet-related changes by parenteral nutrition lipid emulsions in human studies. Studies have pointed out patients at risk of bleeding and increased platelet aggregation responses due to the administration of lipid emulsions. Lipid emulsions may further benefit patients at high risk of thrombosis due to anti-thrombotic effects and should be cautiously used in patients with thrombocytopenia. The reported platelet-related changes might be associated with the fatty acid change in the plasma membranes of platelets following changes in platelet synthesis and plasma levels of eicosanoids. In conclusion, studies investigating platelets and parenteral nutrition should be supported to minimize the adverse effects and to benefit from the potential protective effects of parenteral nutrition lipid emulsions.

Evaluation of the effectiveness of third-generation lipid emulsion therapy for early pregnancy loss

BACKGROUND: Immune mechanisms play an important role in the pathogenesis of early pregnancy loss. To regulate disorders of immune homeostasis, immunoefferent therapy is used, such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and lipid emulsions, which may help to overcome infertility and recurrent miscarriage. Third-generation lipid emulsion (TGLE) is the modern “gold standard” of parenteral lipid therapy. It contains high concentrations of omega-3-polyunsaturated fatty acids, which can directly or indirectly affect the activity of natural killer (NK) cells. The literature comprises contradictory data on the efficacy of TGLE for repeated implantation failure. This may be due to the determination of biochemical parameters for its use and the selection of criteria for assessing the effectiveness of this therapy.&#x0D; AIM: The aim of this study was to evaluate the effectiveness of TGLE therapy in patients with a history of early pregnancy loss.&#x0D; MATERIALS AND METHODS: This prospective randomized controlled study enrolled 140 patients with early pregnancy loss (recurrent miscarriage and repeated implantation failure) at the Research Institute of Obstetrics, Gynecology and Reproducto logy named after D.O. Ott, Saint Petersburg, Russia from 2021 to 2023. Group 1 consisted of 50 women with TGLE therapy, and group 2 included 90 women without therapy. Patients of group 1 received lipid therapy according to the following regimen: TGLE 20% IV 6 ml per kilogram of body weight once a month for two months on end. Inclusion criteria: women from 18 to 45 years of age with two cases of reproductive failure – pregnancy loss up to 12 weeks of gestation and/or unsuccessful in vitro fertilization attempts (embryo transfers without effect) with normal karyotypes of the spouses. Exclusion criteria: women with miscarriage with an abnormal karyotype of the fetus, with anatomical abnormalities in the development of the reproductive apparatus, with an abnormal karyotype of any of the spouses, with hypersensitivity to omega-3 polyunsaturated fatty acids. We assessed the omega-3 index, functional characteristics of NK cells in the peripheral blood, and the effectiveness of lipid therapy based on biochemical and immunological parameters, as well as the clinical onset of pregnancy.&#x0D; RESULTS: The difference in the omega-3 index before and after treatment with TGLE was significant (p = 0.0002), this parameter being increased by 1.23 times compared to the initial level. The functional activity of NK cells in the blood was significantly different after the administration of TGLE: NK (CD3–CD(16+56+)) (p = 0.0041), NKT (CD3+CD(16+56+)) (p = 0.0498), and spontaneously activated NK (CD107a) (p = 0.0498). These parameters decreased by 1.63, 1.29, and 2.07 times relative to their initial levels. In group 1 of patients receiving TGLE therapy, clinical pregnancy occurred twice as often as compared to those who did not receive this therapy (56.41%, n = 22 vs. 31.25%, n = 20; p = 0.01).&#x0D; CONCLUSIONS: TGLE has shown effectiveness in pregnancy rates by increasing the omega-3 index and reducing the functional activity of NK cells in women with early pregnancy loss.

Effects of Intravenous Lipid Emulsion Administration in Acute Tramadol Poisoning: A Randomized Controlled Trial

BackgroundAs the prevalence of tramadol toxicity is increasing, managing these patients with the aim of treatment and complete recovery has become a major challenge for health care professionals. ObjectiveThis study evaluated the short-term effects of IV lipid emulsion (ILE) administration in cases of tramadol poisoning. MethodsIn this double-blind, randomized controlled trial, 120 patients with pure tramadol poisoning and a Glasgow Coma (GCS) score ≤ 12 referred to a poisoning center in Tehran, Iran were selected and randomly assigned 1:1 to receive ILE 20% (intervention) or 0.9% saline (control) after admission and primary stabilization. The patient's vital signs, GCS score, hospitalization duration, and rate of seizure occurrence were recorded and compared between the two groups. ResultsMean (SD) age of participants was 25.3 (5.4) years and 84 (70%) were male. Mean (SD) ingested dose of tramadol was 3118 (244) mg, which was not different between the groups. Compared with controls, the ILE group had a higher level of consciousness after treatment (median [interquartile range] GCS score 12 [10–13] vs. 10 [8–12]; p = 0.03). In addition, length of hospitalization (median [interquartile range] (2 [1–3] days vs. 4 [4–6] days; p < 0.01) and rate of seizure occurrence were lower in the intervention group (16/60 vs. 30/60; p < 0.01). ConclusionsIn the setting of tramadol poisoning with a decreased level of consciousness and based on our study's findings, administration of ILE is suggested to help manage patients in hospital emergency departments. However, larger trials might be needed to confirm these findings before entering the guidelines.

BDNF-TrkB/proBDNF-p75NTR pathway regulation by lipid emulsion rescues bupivacaine-induced central neurotoxicity in rats

Bupivacaine (BPV) can cause severe central nervous system toxicity when absorbed into the blood circulation system. Rapid intravenous administration of lipid emulsion (LE) could be used to treat local anaesthetic toxicity. This study aimed to investigate the mechanism by which the BDNF-TrkB/proBDNF-p75NTR pathway regulation by LE rescues BPV induced neurotoxicity in hippocampal neurons in rats. Seven- to nine-day-old primary cultured hippocampal neurons were randomly divided into 6 groups: the blank control group (Ctrl), the bupivacaine group (BPV), the lipid emulsion group (LE), the bupivacaine + lipid emulsion group (BPV + LE), the bupivacaine + lipid emulsion + tyrosine kinase receptor B (TrkB) inhibitor group (BPV + LE + K252a), the bupivacaine + lipid emulsion + p75 neurotrophic factor receptor (p75NTR) inhibitor group (BPV + LE + TAT-Pep5). All hippocampal neurons were incubated for 24 h, and their growth state was observed by light microscopy. The relative TrkB and p75NTR mRNA levels were detected by real-time PCR. The protein expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, TrkB, p75NTR and cleaved caspase-3 were detected by western blotting. The results showed that primary hippocampal neuron activity was reduced by BPV. As administration of LE elevated hippocampal neuronal activity, morphology was also somewhat improved. The protein expression and mRNA levels of TrkB and p75NTR were decreased when BPV induced hippocampal neuronal toxicity, while the expression of BDNF was increased. At the same time, BPV increased the original generation of cleaved caspase-3 protein content by hippocampal neurons, while the content of cleaved caspase-3 protein in hippocampal neurons cotreated with LE and BPV was decreased. Thus, this study has revealed LE may reduce apoptosis and promote survival of hippocampal neurons by regulating the BDNF-TrkB pathway and the proBDNF-p75NTR pathway to rescue BPV induced central neurotoxicity in rats.

Gooseberry anthocyanins alleviate insulin resistance by regulating ceramide metabolism in high fat diet mice.

Obesity is the fifth largest risk factor of death in the world. The ceramide produced by obesity is closely related to insulin resistance (IR) caused by obesity. At present, the commercially available weight loss products have large side effects and limited therapeutic effects. Therefore, it is particularly important to find effective natural nontoxic products to treat obesity and explore its possible pathways and mechanisms. In this paper, a high-fat diet (HFD) mice model was established by intragastric administration of high-fat emulsion to investigate the intervention effect of Gooseberry anthocyanins (GA) on IR in HFD mice. We used molecular docking technology to find the binding sites and binding energy of anthocyanins on CerS6. Real-time PCR was used to detect the effect of GA on the expression of IL-6 and TNF-α mRNA in HFD mice. The expression of S1P/Cer signaling pathway in HFD mice with IR was detected by Western Blot. The results showed that GA could effectively inhibit visceral fat, liver index, the level of TC, TG and the level of LDL-C (p < 0.05), and improved HDL-C, GSH-Px and SOD (p < 0.05). GA decreased the level of insulin sensitivity index from -5.15 to -4.54 and improved insulin sensitivity and IR in HFD mice. The binding energy of anthocyanins on CerS6 was in the range of -8.2 to 5.2 kcal/mol, with low energy parameters and good binding positions. GA could reduce mRNA levels of inflammatory factors IL-6 and TNF-α (p < 0.05), inhibit the expression of CerS6, PKCζ, PPARγ, CD36 (p < 0.05), and enhance the expression of SphK2, Akt, p-Akt/Akt, ISR (p < 0.05). This study investigated the effect and mechanism of GA on reducing ceramide content and reducing IR in mice, and provided an experimental basis for the prevention and treatment of obesity-related diseases.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study

Background Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The “lipid sink” theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant’s degree of lipophilicity. Methods We reviewed all cases in the Toxicology Investigators Consortium’s lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant’s octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. Results We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. Conclusion Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Effect of fat emulsion administration on blood coagulation in terminal lung cancer patients.

Patients with cancer, especially those with lung cancer, are at high risk of developing thrombosis. Intralipos® infusion 20% is contraindicated for thrombosis, and there is no consensus on whether it can be safely used in cases of advanced cancer. We conducted a retrospective observational study to elucidate the impact of fat emulsion administration on blood coagulation in patients with terminal lung cancer. The subjects were patients with terminal lung cancer in the Department of Surgery and Palliative Medicine, Fujita Health University Nanakuri Memorial Hospital between January 2016 and December 2019. We compared changes in their blood coagulation profile before hospitalization and one month later. There were a total of 213 patients with lung cancer-139 who were administered fat emulsion and 74 who were not-with no significant differences in baseline characteristics. In the fat emulsion administration group (n=27), the prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (APTT), respectively, were 1.17±0.26 (mean±standard deviation) and 30.5±5.0s at hospitalization and 1.16±0.12 and 31.2±4.2s one month later with no significant differences. In the non-administration group (n=6), the PT-INR and APTT, respectively, were 1.44±0.43 and 30.6±5.2s before hospitalization and 1.28±0.18 and 33.0±7.5s one month later with no significant differences. We did not identify any changes in PT-INR and APTT after fat emulsion administration in patients with terminal lung cancer. There were also no new cases of thrombosis, suggesting that fat emulsions were administered safely in patients with terminal lung cancer.

The lipid-lowering effects of fenugreek gum, hawthorn pectin, and burdock inulin.

The present study aimed to investigate the lipid-lowering effects and mechanisms of fenugreek gum (FG), hawthorn pectin (HP), and burdock inulin (BI) on high-fat diet (HFD)-induced hyperlipidemic rats. In this study, high-fat diet (HFD) together with fat emulsion administration were used to establish hyperlipidemia model. The biochemical indices were assayed after administration of FG, HP, and BI. Their effects were evaluated by factor analysis. Alterations of gut microbiota and short chain fatty acids (SCFAs) in the cecal were assessed to illustrate the mechanism of lipid lowering. The supplementation of FG, HP, and BI on HFD-fed rats decreased the levels of serum lipid and reduced the HFD-related liver and testicle damage. In the scatter plot of factor analysis, HP and BI were closer to normal fat diet (NFD) group in restoring the severity of hyperlipidemia, while FG and HP enhanced the excretion of cholesterol and bile acids (BAs). The levels of total SCFAs, especially butyric acid reduced by HFD were increased by HP. The ratio of Firmicutes to Bacteroidetes increased by HFD was reduced by HP and BI. FG, HP, and BI enriched intestinal probiotics, which were related to bile acid excretion or lipid-lowering. FG inhibited the absorption of cholesterol and enhanced the excretion of it, as well as increased the abundance of beneficial bacteria. While BI restored the imbalance of intestinal microbiota. HP enhanced the excretion of cholesterol and BAs, and restored the imbalance of intestinal microbiota. It was also utilized by intestinal microorganisms to yield SCFAs. This study suggested that FG, HP, and BI possessed the potential to be utilized as dietary supplements for obesity management.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Efficiency of intravenous therapy with Intralipid fat emulsion in patients with early reproductive loss

BACKGROUND: Immune mechanisms play a leading role in the pathogenesis of early reproductive loss. Modern methods of regulating disorders of immune homeostasis to overcome infertility and recurrent miscarriage include immune-efferent therapies such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and fat emulsions. Intralipid is the gold standard of the first generation parenteral fat emulsion that reduces the cytotoxicity of NK cells. In the literature, there are opposite data on the effectiveness of Intralipid fat emulsion in repeated implantation failure. This may be due to indications for its appointment and the choice of criteria for evaluating the effectiveness of this therapy.&#x0D; AIM: The aim of this study was to evaluate the effect of Intralipid therapy on the onset of pregnancy in patients with a history of early reproductive loss.&#x0D; MATERIALS AND METHODS: This prospective cohort study was conducted in Saint Petersburg, Russia in 20182021 and included 97 patients with a history of early reproductive loss (recurrent pregnancy loss or repeated In Vitro Fertilization failures). Patients were randomized into two study groups. The first group consisted of 41 women with Intralipid therapy, and the second group comprised 56 women without this therapy. Patients of the first group received 200 ml of Intralipid 20% (intravenous fat emulsion) once a month for three consecutive months before pregnancy. Inclusion criteria were ages 18 to 40 years, two cases of reproductive failure (pregnancy loss up to 12 weeks and / or unsuccessful In Vitro Fertilization attempts), and normal spouse karyotypes. Exclusion criteria were miscarriage due to fetal chromosomal abnormalities diagnosed by curettage and histopathological examination of products of conception from miscarriages, anatomical anomalies in the development of the genital apparatus, abnormal spouse karyotypes, and soy protein allergy. We evaluated anamnesis data and immunological parameters (functional activity of NK cells in peripheral blood before and after treatment). The efficacy of therapy was judged by the onset of pregnancy.&#x0D; RESULTS: The Mann Whitney U-test showed the difference in the levels of NKT cells before and after treatment with fat emulsions (p = 0.0076), this parameter decreasing 1.846 times compared to control. Clinical pregnancy in patients treated with Intralipid occurred twice as often compared to patients who did not receive fat emulsion therapy: 59.3% (n = 19) vs. 27.6% (n = 13), respectively (p = 0.0048).&#x0D; CONCLUSIONS: Intralipid fat emulsion increases pregnancy rates by decreasing NKT cells in women with early reproductive loss.

Dietary triacylglycerol hydroperoxide is not absorbed, yet it induces the formation of other triacylglycerol hydroperoxides in the gastrointestinal tract

The in vivo presence of triacylglycerol hydroperoxide (TGOOH), a primary oxidation product of triacylglycerol (TG), has been speculated to be involved in various diseases. Thus, considerable attention has been paid to whether dietary TGOOH is absorbed from the intestine. In this study, we performed the lymph duct-cannulation study in rats and analyzed the level of TGOOH in lymph following administration of a TG emulsion containing TGOOH. As we successfully detected TGOOH from the lymph, we hypothesized that this might be originated from the intestinal absorption of dietary TGOOH [hypothesis I] and/or the in situ formation of TGOOH [hypothesis II]. To determine the validity of these hypotheses, we then performed another cannulation study using a TG emulsion containing a deuterium-labeled TGOOH (D2-TGOOH) that is traceable in vivo. After administration of this emulsion to rats, we clearly detected unlabeled TGOOH instead of D2-TGOOH from the lymph, indicating that TGOOH is not absorbed from the intestine but is more likely to be produced in situ. By discriminating the isomeric structures of TGOOH present in lymph, we predicted the mechanism by which the intake of dietary TGOOH triggers oxidative stress (e.g., via generation of singlet oxygen) and induces in situ formation of TGOOH. The results of this study hereby provide a foothold to better understand the physiological significance of TGOOH on human health.