Clinical prediction of wound re-epithelisation outcomes in non-severe burn injury using the plasma lipidome.

Whilst wound repair in severe burns has received substantial research attention, non-severe burns (<20 % total body surface area) remain relatively understudied, despite causing considerable physiological impact and constituting most of the hospital admissions for burns. Early prediction of healing outcomes would decrease financial and patient burden, and aid in preventing long-term complications from poor wound healing. Lipids have been implicated in inflammation and tissue repair and may play essential roles in burn wound healing.

H NMR spectroscopic characterisation of HepG2 cells as a model metabolic system for toxicology studies.

The immortalised human hepatocellular HepG2 cell line is commonly used for toxicology studies as an alternative to animal testing due to its characteristic liver-distinctive functions. However, little is known about the baseline metabolic changes within these cells upon toxin exposure. We have applied H Nuclear Magnetic Resonance (NMR) spectroscopy to characterise the biochemical composition of HepG2 cells at baseline and post-exposure to hydrogen peroxide (HO).

Nonsevere Burn Induces a Prolonged Systemic Metabolic Phenotype Indicative of a Persistent Inflammatory Response Postinjury.

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of a nonsevere burn injury, longitudinal plasma was collected from adults ( = 35) who presented at hospital with a nonsevere burn injury at admission, and at 6 week follow up.

Comprehensive Lipidomic Workflow for Multicohort Population Phenotyping Using Stable Isotope Dilution Targeted Liquid Chromatography-Mass Spectrometry.

Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, requiring advanced methods that are accurate and robust to batch-to-batch and interday analytical variation.

Branched-chain amino acid supplementation improves cycling performance in untrained cyclists.

Objectives: To investigate the effects of acute branched-chain amino acid (BCAA) supplementation on cycling performance and neuromuscular fatigue during a prolonged, self-paced cycling time-trial.

Design: Randomised double-blind counterbalanced crossover.

Methods: Eighteen recreationally active men (mean±SD; age: 24.

Sample Preparation and Reporting Standards for Metabolomics of Adherent Mammalian Cells.

Metabolomics is an analytical technique that investigates the small molecules present within a biological system. Metabolomics of cultured cells allows profiling of the metabolic chemicals involved in a cell type-specific system and the response of that metabolome to external challenges, such as change in environment or exposure to drugs or toxins. The numerous benefits of in vitro metabolomics include a much greater control of external variables and reduced ethical concerns.

Untargeted gas chromatography-mass spectrometry-based metabolomics analysis of kidney and liver tissue from the Lewis Polycystic Kidney rat.

Polycystic kidney disease (PKD) encompasses a spectrum of inherited disorders that lead to end-stage renal disease (ESRD). There is no cure for PKD and current treatment options are limited to renal replacement therapy and transplantation. A better understanding of the pathobiology of PKD is needed for the development of new, less invasive treatments.

Metabolomics Approaches for the Diagnosis and Understanding of Kidney Diseases.

Diseases of the kidney are difficult to diagnose and treat. This review summarises the definition, cause, epidemiology and treatment of some of these diseases including chronic kidney disease, diabetic nephropathy, acute kidney injury, kidney cancer, kidney transplantation and polycystic kidney diseases. Numerous studies have adopted a metabolomics approach to uncover new small molecule biomarkers of kidney diseases to improve specificity and sensitivity of diagnosis and to uncover biochemical mechanisms that may elucidate the cause and progression of these diseases.

Characterizing the plasma metabolome during 14 days of live-high, train-low simulated altitude: A metabolomic approach.

New Findings: What is the central question of this study? Does 14 days of live-high, train-low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance? This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude.

Characterizing the plasma metabolome during and following a maximal exercise cycling test.

Although complex in nature, a number of metabolites have been implicated in the onset of exercise-induced fatigue. The purpose of this study was to identify changes in the plasma metabolome and specifically, to identify candidate metabolites associated with the onset of fatigue during prolonged cycling. Eighteen healthy and recreationally active men (mean ± SD; age: 24.

Untargeted Metabolomic Analysis of Rat Neuroblastoma Cells as a Model System to Study the Biochemical Effects of the Acute Administration of Methamphetamine.

Methamphetamine is an illicit psychostimulant drug that is linked to a number of diseases of the nervous system. The downstream biochemical effects of its primary mechanisms are not well understood, and the objective of this study was to investigate whether untargeted metabolomic analysis of an in vitro model could generate data relevant to what is already known about this drug. Rat B50 neuroblastoma cells were treated with 1 mM methamphetamine for 48 h, and both intracellular and extracellular metabolites were profiled using gas chromatography⁻mass spectrometry.

Untargeted metabolomics of neuronal cell culture: A model system for the toxicity testing of insecticide chemical exposure.

Toxicity testing is essential for the protection of human health from exposure to toxic environmental chemicals. As traditional toxicity testing is carried out using animal models, mammalian cell culture models are becoming an increasingly attractive alternative to animal testing. Combining the use of mammalian cell culture models with screening-style molecular profiling technologies, such as metabolomics, can uncover previously unknown biochemical bases of toxicity.

Experimental design and reporting standards for metabolomics studies of mammalian cell lines.

Metabolomics is an analytical technique that investigates the small biochemical molecules present within a biological sample isolated from a plant, animal, or cultured cells. It can be an extremely powerful tool in elucidating the specific metabolic changes within a biological system in response to an environmental challenge such as disease, infection, drugs, or toxins. A historically difficult step in the metabolomics pipeline is in data interpretation to a meaningful biological context, for such high-variability biological samples and in untargeted metabolomics studies that are hypothesis-generating by design.

The Influence of Blood Removal on Pacing During a 4-Minute Cycling Time Trial.

Purpose: To examine the influence of manipulating aerobic contribution after whole-blood removal on pacing patterns, performance, and energy contribution during self-paced middle-distance cycling.

Methods: Seven male cyclists (33 ± 8 y) completed an incremental cycling test followed 20 min later by a 4-min self-paced cycling time trial (4MMP) on 6 separate occasions over 42 d. The initial 2 sessions acted as familiarization and baseline testing, after which 470 mL of blood was removed, with the remaining sessions performed 24 h, 7 d, 21 d, and 42 d after blood removal.

The bioavailability of medetomidine in eight sheep following oesophageal administration.

There is sound evidence that medetomidine is an effective analgesic for acute pain in sheep. In this study, 15 μg kg(-1) of medetomidine was administered intravenously, and into the oesophagus, in a cross-over study, using eight sheep. Following intravenous administration, medetomidine could be detected in the plasma of these sheep for 120-180 min but following oesophageal administration, medetomidine could not be detected in the plasma of any sheep at any of 17 time points over four days.

The potential of metabolomic analysis techniques for the characterisation of α1-adrenergic receptors in cultured N1E-115 mouse neuroblastoma cells.

Several studies of neuropathic pain have linked abnormal adrenergic signalling to the development and maintenance of pain, although the mechanisms underlying this are not yet fully understood. Metabolomic analysis is a technique that can be used to give a snapshot of biochemical status, and can aid in the identification of the mechanisms behind pathological changes identified in cells, tissues and biological fluids. This study aimed to use gas chromatography-mass spectrometry-based metabolomic profiling in combination with reverse transcriptase-polymerase chain reaction and immunocytochemistry to identify functional α1-adrenergic receptors on cultured N1E-115 mouse neuroblastoma cells.

Gas chromatography-mass spectrometry-based metabolite profiling of Salmonella enterica serovar Typhimurium differentiates between biofilm and planktonic phenotypes.

The aim of this study was to utilize gas chromatography coupled with mass spectrometry (GC-MS) to compare and identify patterns of biochemical change between Salmonella cells grown in planktonic and biofilm phases and Salmonella biofilms of different ages. Our results showed a clear separation between planktonic and biofilm modes of growth. The majority of metabolites contributing to variance between planktonic and biofilm supernatants were identified as amino acids, including alanine, glutamic acid, glycine, and ornithine.

Curcumin and major depression: a randomised, double-blind, placebo-controlled trial investigating the potential of peripheral biomarkers to predict treatment response and antidepressant mechanisms of change.

A recent randomised, double-blind, placebo controlled study conducted by our research group, provided partial support for the efficacy of supplementation with a patented curcumin extract (500 mg, twice daily) for 8 weeks in reducing depressive symptoms in people with major depressive disorder. In the present paper, a secondary, exploratory analysis of salivary, urinary and blood biomarkers collected during this study was conducted to identify potential antidepressant mechanisms of action of curcumin. Pre and post-intervention samples were provided by 50 participants diagnosed with major depressive disorder, and the Inventory of Depressive Symptomatology self-rated version (IDS-SR30) was used as the primary depression outcome measure.

Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study.

Background: Curcumin, the principal curcuminoid derived from the spice turmeric, influences several biological mechanisms associated with major depression, namely those associated with monoaminergic activity, immune-inflammatory and oxidative and nitrosative stress pathways, hypothalamus-pituitary-adrenal (HPA) axis activity and neuroprogression. We hypothesised that curcumin would be effective for the treatment of depressive symptoms in individuals with major depressive disorder.

Methods: In a randomised, double-blind, placebo-controlled study, 56 individuals with major depressive disorder were treated with curcumin (500 mg twice daily) or placebo for 8 weeks.

Role of neuregulin-1β in dexamethasone-enhanced surfactant synthesis in fetal type II cells.

It is well established that glucocorticoids elevate the production of fibroblast-pneumocyte factor (FPF), which induces type II cells to synthesize surfactant phospholipids. FPF, however, has not been identified and it is not clear whether it is a single factor or a complex mixture of factors. In this study it has been shown that, when lung fibroblasts are exposed to dexamethasone, the concentration of neuregulin-1β (NRG1β) in conditioned medium is elevated 2-fold (P<0.

Influence of glucocorticoids, neuregulin-1β, and sex on surfactant phospholipid secretion from type II cells.

Glucocorticoids induce lung fibroblasts to produce fibroblast-pneumocyte factor, a peptide that stimulates type II cells to synthesize pulmonary surfactant. This effect is known to be more apparent in cells derived from female fetuses, a characteristic that has been attributed to sex-linked differences in the fibroblasts. In the current study, it has been shown that dexamethasone enhances both β-adrenergic receptor (β-AR) activity (1.

A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers.

Biomarkers are regularly used in medicine to provide objective indicators of normal biological processes, pathogenic processes or pharmacological responses to therapeutic interventions, and have proved invaluable in expanding our understanding and treatment of medical diseases. In the field of psychiatry, assessment and treatment has, however, primarily relied on patient interviews and questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry present a promising addition to advance the diagnosis, treatment and prevention of psychiatric diseases.

Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis.

Aim: Treatment of chronic kidney disease (CKD) includes parenteral iron therapy, and these infusions can lead to iron overload. Secondary iron overload is typically treated with iron chelators, of which deferasirox is one of the most promising. However, it has not been studied in patients with CKD and iron overload.

Development of an untargeted metabolomics method for the analysis of human faecal samples using Cryptosporidium-infected samples.

Faecal metabolite profiling, though in its infancy, allows for investigation of complex metabolic interactions between gastrointestinal infections or diseases and host health. In the present study, we describe a faecal metabolite extraction method for untargeted gas chromatography-mass spectrometry (GC-MS) analysis using Cryptosporidium positive and negative human faecal samples. The extraction method takes into account the varying faecal consistencies and quantities received for clinical diagnosis.

Development of a non-targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease.

Aim: The purpose of this research was to use metabolomics to investigate the cystic phenotype in the Lewis polycystic kidney rat.

Methods: Spot urine samples were collected from four male Lewis control and five male Lewis polycystic kidney rats aged 5 weeks, before kidney function was significantly impaired. Metabolites were extracted from urine and analysed using gas chromatography-mass spectrometry.