scholarly journals Analysis of Lipid-Associated Gene Expression in Mouse Endotoxin Model

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Charles Price ◽  
Takashi Hato
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Low Dose ◽  
Ldl Receptor ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Renal Tissue ◽  
Receptor Expression ◽  
High Dose ◽  
Endotoxemia Model

Background/Objective:   Sepsis-induced kidney injury is a major clinical problem and is an independent risk factor for mortality. We and others have reported that renal tissue metabolism is profoundly altered in the septic milieu. However, whether such metabolic shift is an adaptive response or pathologic process remains unclear. For instance, decreased lipid metabolism in the renal peroxisomes could limit the genesis of deleterious reactive oxygens species whereas the lack of lipid usage in peroxisomes could contribute to energy depletion. Accordingly, here we examined gene expression changes involved in lipid metabolism using mouse models of endotoxemia. Specifically, we compared gene expression changes between injurious high-dose endotoxemia and protective low-dose endotoxin preconditioning models with the goal of identifying favorable reprogramming in lipid metabolism.     Methods:  To induce protective preconditioning, mice were subjected to low-dose endotoxin followed 24 hours later by high-dose endotoxin. Non-preconditioned mice were subjected to a single high-dose endotoxin. Renal tissues were processed and single-cell RNA-sequencing was performed. Tissue metabolomic data was also obtained.     Results:   We found that renal lipid metabolism is deranged in the non-preconditioned endotoxemia model. Plin2, a marker for lipid accumulation, was significantly upregulated in the proximal tubules of non-preconditioned animals. In contrast, Plin2 expression was preserved in the preconditioned animals, suggesting that altered Plin2 expression is a maladaptive response. Similarly, Pdzk1 and Lrp2, genes involved in HDL/LDL receptor expression, were concurrently downregulated in the injurious model, whereas their expression levels were preserved in the protective model. The stable expression of these two genes may be important for maintaining metabolic capacity and anti-inflammatory effects observed in the preconditioned state. These findings were further supported by our tissue metabolomics analysis.     Conclusion/Impact:   Our data indicate that aberrant lipid metabolism is a prominent feature of endotoxin-induced kidney injury. The use of protective preconditioning served as a platform to identify several candidate genes that could be studied further for the development of biomarkers and precise intervention. 

Abstract 11983: Auraptene, a Coumaric Compounds Analogous, Improved the Worsening of Systolic Function by Activating Mitochondrial Function After Myocardial Infarction in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yoichi Sunagawa ◽  
Miho Suzuki ◽  
Masafumi Funamoto ◽  
Yasufumi Katanasaka ◽  
Hidetoshi Suzuki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Lipid Metabolism ◽  
Mitochondrial Function ◽  
Low Dose ◽  
Systolic Function ◽  
Pharmacological Therapy ◽  
Vehicle Group ◽  
High Dose ◽  
Related Gene

Introduction: Heart failure is associated with pathological growth and mitochondrial dysfunction of constituent cardiomyocytes. To achieve effective oral pharmacological therapy for heart failure, we screened compounds isolated from natural products and found that auraptene derived from the peel of Citrus Hassaku may be applicable to pharmacological therapy for heart failure. Hypothesis: We assessed the hypothesis that auraptene could improve the deterioration of mitochondrial function and the development of heart failure in rats with myocardial infarction (MI). Methods and Results: In cultured cardiomyocytes, auraptene (2.5-10 μM) dose-dependently repressed phenylephrine-induced hypertrophic responses such as increase in cell size and ANF and ET-1 promoter activations. Auraptene also activated mitochondrial- and lipid metabolism-related gene transcriptions, such as PGC1α, PPARα/γ, mCPT1, UCP3, and PDK4. One week after operation, 22 rats with a moderate size of MI (Fractional shortening (FS) < 40%) were then randomly assigned to vehicle (n=8), auraptene low-dose (5 mg/kg/day, n=7), or high-dose (50 mg/kg/day, n=7). Oral daily treatments with these agents were continued for 6 weeks. There were no differences in left ventricle (LV) geometric and functional data among the 3 MI groups before treatment. After treatment, LVFS was significantly higher in the auraptene low-dose (21%, p < 0.0001) and high-dose (26%, p < 0.0001) groups than the vehicle group (16%). LV wall thickness in the remote non-infarct area was significantly thinner in the auraptene low-dose (1.4 mm, p < 0.01) and high-dose (1.2 mm, p < 0.0001) groups than the vehicle group (2.5 mm). Histological analysis demonstrated that auraptene treatment significantly suppressed MI-induced increases in myocardial cell diameter and perivascular fibrosis compared with vehicle treatment. Moreover, auraptene also prevented the activations of ANF and MCP-1 mRNA levels and up-regulated mitochondrial- and lipid metabolism-related gene transcriptions in LV. Conclusions: Auraptene treatment prevents the worsening of LV systolic function and represses hypertrophy after MI in adult rats. A natural compound, auraptene is expected as a novel useful agent for heart failure therapy in humans.

scholarly journals Original Article. Inflammatory effect of 2-aminoanthracene (2AA) on adipose tissue gene expression in pregnant Sprague Dawley rats

2016 ◽  
Vol 9 (1) ◽  
pp. 17-24
Author(s):  
Shamaya L. Whitby ◽  
Daniel A. Hunter ◽  
Wilson Yau ◽  
Elizabeth W. Howerth ◽  
Worlanyo E. Gato
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dose Group ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Postnatal Period ◽  
High Dose ◽  
Sprague Dawley ◽  
Polycyclic Aromatic ◽  
Altered Gene

Abstract Adipocyte dysfunction may be a critical link between obesity and insulin resistance as a result of abnormal fat storage and mobilization. Adipocytes uniquely secrete adipokines and cytokines, such as leptin and TNFα, wich promote insulin sensitivity. Previously we reported insulin-signaling related altered gene expression in animals exposed to 2-Aminoanthracene (2AA). 2AA is an aminosubstituted polycyclic aromatic hydrocarbon used in manufacturing dyes, chemicals, inks, resins, and polyurethanes. The objective of this study was to examine the inflammation related effects of 2AA exposure from gestation to postnatal period on dams that ingested 2AA. To examine 2AA effects, pregnant dams were assigned into dose regimens of 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. The expression of key gene transcripts reported to be important in mediating inflammatory processes was examined via quantitative RT-PCR. Histologic examination of adipose tissue (AT) was also carried out to understand the anatomy of AT due to 2AA exposure during gestation and two weeks postpartum. Examination of the adipose tissue for microscopic changes revealed no alterations between control and low-dose animals. However, AT of the high-dose animals was infiltrated by increased numbers of CD68+mononuclear cells (macrophages) and small numbers of eosinophils and mast cells, consistent with inflammation. In addition, analysis of the mRNA expression of cytokines and adipokines demonstrated the importance of inflammation in AT dysfunction. For instance, TNFα, LEPTIN and IL-6 transcripts were relatively more expressed in the low dose animals than in the high dose and control rats. At the protein level, however, high amounts of cytokines were noted. The effects of 2AA on pregnant dams appear to be more pronounced in the high dose group than in the low dose group, possibly indicating increased susceptibility of rat offspring within this group to elicit a diabetic-type response.

scholarly journals High-dose versus low-dose haemofiltration for the treatment of critically ill patients with acute kidney injury: an updated systematic review and meta-analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e014171 ◽  
Author(s):  
Peng Li ◽  
Li-ping Qu ◽  
Dong Qi ◽  
Bo Shen ◽  
Yi-mei Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Acute Kidney Injury ◽  
Hospital Mortality ◽  
Hospital Stay ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Low Dose ◽  
Meta Analysis ◽  
Kidney Injury ◽  
High Dose

ObjectiveThe purpose of this study was to perform a systematic review and meta-analysis to evaluate the effect of high-dose versus low-dose haemofiltration on the survival of critically ill patients with acute kidney injury (AKI). We hypothesised that high-dose treatments are not associated with a higher risk of mortality.DesignMeta-analysis.SettingRandomised controlled trials and two-arm prospective and retrospective studies were included.ParticipantsCritically ill patients with AKI.InterventionsContinuous renal replacement therapy.Primary and secondary outcome measuresPrimary outcomes: 90-day mortality, intensive care unit (ICU) mortality, hospital mortality; secondary outcomes: length of ICU and hospital stay.ResultEight studies including 2970 patients were included in the analysis. Pooled results showed no significant difference in the 90-mortality rate between patients treated with high-dose or low-dose haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and hospital stay were similar between high-dose and low-dose groups. Pooled results are not overly influenced by any one study, different cut-off points of prescribed dose or different cut-off points of delivered dose. Meta-regression analysis indicated that the results were not affected by the percentage of patients with sepsis or septic shock.ConclusionHigh-dose and low-dose haemofiltration produce similar outcomes with respect to mortality and length of ICU and hospital stay in critically ill patients with AKI.This study was not registered at the time the data were collected and analysed. It has since been registered on 17 February 2017 athttp://www.researchregistry.com/, registration number: reviewregistry211.

scholarly journals High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse

2015 ◽  
Vol 309 (3) ◽  
pp. R223-R234 ◽  
Author(s):  
Asada Leelahavanichkul ◽  
Poorichaya Somparn ◽  
Tanabodee Bootprapan ◽  
Hongbin Tu ◽  
Pattarin Tangtanatakul ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Mouse Model ◽  
Amphotericin B ◽  
Low Dose ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Sodium Deoxycholate ◽  
High Dose ◽  
Phagocytic Cells

Amphotericin B (Ampho B) is a fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically. We tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression in patients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with <11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage, liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.

Role of oxidized LDL and lectin-like oxidized LDL receptor-1 in cerebral vasospasm after subarachnoid hemorrhage

2014 ◽  
Vol 121 (3) ◽  
pp. 621-630 ◽  
Author(s):  
Naoya Matsuda ◽  
Hiroki Ohkuma ◽  
Masato Naraoka ◽  
Akira Munakata ◽  
Norihito Shimamura ◽  
...  
Keyword(s):  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Low Dose ◽  
Oxidized Ldl ◽  
Ldl Receptor ◽  
Cross Sectional Area ◽  
High Dose ◽  
Sectional Area ◽  
Cross Sectional ◽  
The Cross

Object Cerebral vasospasm after subarachnoid hemorrhage (SAH) is a serious complication. Free radicals derived from subarachnoid clotting are recognized to play an important role. Oxidized low-density lipoprotein (ox-LDL) and lectin-like oxidized LDL receptor-1 (LOX-1) have been shown to be related to the pathogenesis of atherosclerosis and may increase in cerebral arteries after SAH, due to the action of free radicals derived from a subarachnoid clot. These molecules may also affect the pathogenesis of vasospasm, generating intracellular reactive oxygen species and downregulating the expression of endothelial NO synthase (eNOS). If so, apple polyphenol might be effective in the prevention of vasospasm due to an abundant content of procyanidins, which exhibit strong radical scavenging effects, and the ability to suppress ox-LDL and LOX-1. The purposes of this study were to investigate changes in levels of ox-LDL and LOX-1 after SAH and whether administering apple polyphenol can modify cerebral vasospasm. Methods Forty Japanese white rabbits were assigned randomly to 4 groups: an SAH group (n = 10); a shamoperation group (n = 10), which underwent intracisternal saline injection; a low-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 10 mg/kg per day from Day 0 to Day 3; and a high-dose polyphenol group (n = 10) with SAH and oral administration of apple polyphenol at 50 mg/kg per day. At Day 4, the basilar artery and brain was excised from each rabbit. The degree of cerebral vasospasm was evaluated by measuring the cross-sectional area of each basilar artery, and the expression of ox-LDL, LOX-1, and eNOS was examined for each basilar artery by immunohistochemical staining and reverse transcriptase polymerase chain reaction. In addition, neuronal apoptosis in the cerebral cortex was evaluated by TUNEL. Results Compared with the sham group, the expression of ox-LDL and LOX-1 in the basilar arterial wall was significantly increased in the SAH group, the expression of eNOS was significantly decreased, and the cross-sectional area of basilar artery was significantly decreased. Compared with the SAH group, the cross-sectional area of basilar artery was increased in the polyphenol groups, together with the decreased expression of ox-LDL and LOX-1 and the increased expression of eNOS. In the high-dose polyphenol group, those changes were statistically significant compared with the SAH group. In the low-dose polyphenol group, those changes were smaller than in the high-dose polyphenol group. No apoptosis and no changes were seen in the cerebral cortex in all groups. Conclusions This is the first study suggesting that ox-LDL and LOX-1 increase due to SAH and that they may play a role in the pathogenesis of vasospasm. It is assumed that procyanidins in apple polyphenol may inhibit a vicious cycle of ox-LDL, LOX-1, and ROS in a dose-dependent manner. Apple polyphenol is a candidate for preventive treatment of cerebral vasospasm.

scholarly journals Recently published papers: Renal support in acute kidney injury - is low dose the new high dose?

Critical Care ◽  
2009 ◽  
Vol 13 (6) ◽  
pp. 1014
Author(s):  
Yadullah Syed ◽  
James AP Tomlinson ◽  
Lui G Forni
Keyword(s):  
Acute Kidney Injury ◽  
Low Dose ◽  
Kidney Injury ◽  
High Dose ◽  
Renal Support

Differential Effects of Low-Dose and High-Dose Beta-Carotene Supplementation on the Signs of Photoaging and Type I Procollagen Gene Expression in Human Skin in vivo

Dermatology ◽  
2010 ◽  
Vol 221 (2) ◽  
pp. 160-171 ◽  
Author(s):  
Soyun Cho ◽  
Dong Hun Lee ◽  
Chong-Hyun Won ◽  
Sang Min Kim ◽  
Serah Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Skin ◽  
Low Dose ◽  
Beta Carotene ◽  
High Dose ◽  
Type I ◽  
Differential Effects ◽  
Type I Procollagen

The Direct Interactions with Bone Marrow Microenvironment Confer Resistance to the Inhibition of Oxidative Phosphorylation in AML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Yoko Tabe ◽  
Kaori Saito ◽  
Kotoko Yamatani ◽  
Haeun Yang ◽  
Rodrigo Jacamo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Mouse Models ◽  
Stromal Cells ◽  
Research Funding ◽  
Ldl Receptor ◽  
Leukemia Cells ◽  
Related Protein ◽  
Resistant Mouse ◽  
Argininosuccinate Synthase

Acute myeloid leukemia (AML) cells are highly dependent on oxidative phosphorylation (OxPhos) for survival and continually adapt to the bone marrow (BM) microenvironment. We investigated how the BM microenvironment impacts the response to energy-depriving OxPhos inhibition in AML using a novel complex I OxPhos inhibitor (OxPhosi), IACS-010759. We have reported that OxPhosi-resistant primary AML samples demonstrated higher baseline transcription of genes related to cell adhesion, integrin and/or Rho GTPase family genes that modulate intracellular actin dynamics. (Yang et al. ASH 2019) In this study, we performed Cap Analysis of Gene Expression (CAGE) transcriptome analyses using IACS-010759-sensitive and -resistant AML PDXs. CAGE identifies and quantifies the 5' ends of capped mRNA transcripts (= transcription start sites) and allows investigating promoter structures necessary for gene expression. Primary AML cells from 9 AML PDXs were injected into irradiated NSG mice, which were randomized upon documented engraftment to receive IACS-010759 or vehicle (n = 3/group). The antileukemia efficacy of the treatment was monitored by serial measurements of circulating AML cells. Of the 9 models tested, we defined 4 PDXs as sensitive and 5 as resistant to OxPhos inhibitor therapy. In the resistant models, CAGE analysis of OxPhosi-induced changes (comparing pretreatment with posttreatment) identified upregulation of 77 promoters and downregulation of 207 promoters (log 2-fold change &gt; 3.0, FDR &lt; 0.05, EdgeR), including increased promoter expression (&gt;3.0 fold) of genes associated with adhesion (CCR8,ADGRB2, LAG3, BMF, ATN1, PLXDC1), migration (CCR8, NKX3-2, TMEM123, IGLV7-43, FAM171A1, LBX2, TRAV21, PPP2R5C, BMF, PLXDC1), and actin cytoskeleton dynamics (FAM171A1, BMF, BEST1, PLXDC1). Of note, the 6 adhesion-associated promoters that were upregulated by OxPhosi in 5 of the OxPhosi-resistant mouse models were unchanged or downregulated in the 4 OxPhosi-sensitive models. We then used DEGseq, an R package for identifying differentially expressed genes, to identify promoters whose expression was different between OxPhosi-treated and vehicle-treated groups in the OxPhosi-resistant mouse models. DEGseq detected consistent changes of 214 upregulated and 626 downregulated promoters with OxPhosi treatment in all 5 mouse models. KEGG pathway enrichment analysis was performed with these consistently changed genes and revealed that OxPhos inhibitor treatment significantly upregulated the transcripts of cell adhesion pathway. We then confirmed that BM derived mesenchymal stem cells (MSC) protected OxPhosi-sensitive OCI-AML3 cells; the IC50 of IACS-010759 under MSC coculture was 80-fold higher than in monoculture conditions (IC50; 0.04 nM in monoculture vs. 3.25 nM in coculture), and IACS-010759 (10nM) induced 55% reduction of viable cells in coculture condition as compared to 70% reduction in monoculture. We further observed that OCI-AML3 cells adhered to MSCs were more profoundly protected from OxPhosi induced apoptosis than nonadherent cells. These results indicate that BM stromal cells, in particular those in direct contact with leukemia cells, play a key role in the microenvironment-mediated protection of AML cells from metabolic stress caused by OxPhos blockade. We further observed promoter upregulation of ASS1, coding Argininosuccinate Synthase 1 and of LRP1, coding LDL Receptor Related Protein 1. Argininosuccinate Synthase 1 is an epigenetically regulated key enzyme in the biosynthesis of arginine and energy starvation that induces adaptive transcriptional upregulation of ASS1. LDL Receptor Related Protein 1 plays a major role in lipid metabolism and has been reported to be responsible for hemin-induced autophagy in leukemia cells. These might contribute to intrinsic AML resistance to OxPhosi via activation of compensatory metabolic pathways, amino acid metabolism and lipid metabolism. Taken together, our data highlight the importance of direct interaction with BM stromal cells as well as complementally modification of amino acid- and lipid metabolism for the resistance of AML cells to OxPhos inhibition. While the mechanisms of stroma-leukemia interactions are likely complex, reducing the adhesion of AML cells to nurturing stromal cells ameliorates the resistance to the metabolic and energetic consequences of OxPhos inhibition. Disclosures Andreeff: Amgen: Research Funding; Centre for Drug Research & Development; Cancer UK; NCI-CTEP; German Research Council; Leukemia Lymphoma Foundation (LLS); NCI-RDCRN (Rare Disease Clin Network); CLL Founcdation; BioLineRx; SentiBio; Aptose Biosciences, Inc: Membership on an entity's Board of Directors or advisory committees; Daiichi-Sankyo; Jazz Pharmaceuticals; Celgene; Amgen; AstraZeneca; 6 Dimensions Capital: Consultancy; Daiichi-Sankyo; Breast Cancer Research Foundation; CPRIT; NIH/NCI; Amgen; AstraZeneca: Research Funding. Konopleva:Rafael Pharmaceutical: Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Sanofi: Research Funding; AstraZeneca: Research Funding; Cellectis: Research Funding; AbbVie: Consultancy, Research Funding; Ablynx: Research Funding; Agios: Research Funding; Ascentage: Research Funding; Eli Lilly: Research Funding; Forty-Seven: Consultancy, Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Amgen: Consultancy; F. Hoffmann La-Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Kisoji: Consultancy; Calithera: Research Funding.

Safety, Pharmacodynamics, and Efficacy of High- Versus Low-Dose Ascorbic Acid in Severely Burned Adults

2020 ◽  
Vol 41 (4) ◽  
pp. 871-877
Author(s):  
Sarah Sophie Nagel ◽  
Christian Andreas Radu ◽  
Thomas Kremer ◽  
David Meess ◽  
Johannes Horter ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Retrospective Study ◽  
Clinical Outcomes ◽  
Low Dose ◽  
Kidney Injury ◽  
High Dose ◽  
Severe Burns ◽  
Increased Risk ◽  
Before And After ◽  
Resuscitation Fluid

Abstract In sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns &gt;20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid–base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA.

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