Research

13 pages, 1934 KiB

Open AccessArticle

Non-Invasive O-Toluidine Monitoring during Regional Anaesthesia with Prilocaine and Detection of Accidental Intravenous Injection in an Animal Model

by Beate Brock, Patricia Fuchs, Svend Kamysek, Udo Walther, Selina Traxler, Giovanni Pugliese, Wolfram Miekisch, Jochen K. Schubert and Phillip Trefz

Metabolites 2022, 12(6), 502; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo12060502 - 31 May 2022

Viewed by 1369

Abstract

Regional anaesthesia is well established as a standard method in clinical practice. Currently, the local anaesthetics of amino-amide types such as prilocaine are frequently used. Despite routine use, complications due to overdose or accidental intravenous injection can arise. A non-invasive method that can [...] Read more.

Regional anaesthesia is well established as a standard method in clinical practice. Currently, the local anaesthetics of amino-amide types such as prilocaine are frequently used. Despite routine use, complications due to overdose or accidental intravenous injection can arise. A non-invasive method that can indicate such complications early would be desirable. Breath gas analysis offers great potential for the non-invasive monitoring of drugs and their volatile metabolites. The physicochemical properties of o-toluidine, the main metabolite of prilocaine, allow its detection in breath gas. Within this study, we investigated whether o-toluidine can be monitored in exhaled breath during regional anaesthesia in an animal model, if correlations between o-toluidine and prilocaine blood levels exist and if accidental intravenous injections are detectable by o-toluidine breath monitoring. Continuous o-toluidine monitoring was possible during regional anaesthesia of the cervical plexus and during simulated accidental intravenous injection of prilocaine. The time course of exhaled o-toluidine concentrations considerably differed depending on the injection site. Intravenous injection led to an immediate increase in exhaled o-toluidine concentrations within 2 min, earlier peak and higher maximum concentrations, followed by a faster decay compared to regional anaesthesia. The strength of correlation of blood and breath parameters depended on the injection site. In conclusion, real time monitoring of o-toluidine in breath gas is possible by means of PTR-ToF-MS. Since simulated accidental intravenous injection led to an immediate increase in exhaled o-toluidine concentrations within 2 min and higher maximum concentrations, monitoring exhaled o-toluidine may potentially be applied for the non-invasive real-time detection of accidental intravenous injection of prilocaine. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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12 pages, 9549 KiB

Open AccessArticle

Urinary Metabolomic Profile of Neonates Born to Women with Gestational Diabetes Mellitus

by Ana Sofía Herrera-Van Oostdam, Mariana Salgado-Bustamante, Victoria Lima-Rogel, Juan José Oropeza-Valdez, Jesús Adrián López, Iván Daniel Román Rodríguez, Juan Carlos Toro-Ortiz, David Alejandro Herrera-Van Oostdam, Yamilé López-Hernández and Joel Monárrez-Espino

Metabolites 2021, 11(11), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11110723 - 22 Oct 2021

Cited by 3 | Viewed by 2274

Abstract

Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications with potential adverse outcomes for mothers and newborns. Its effects on the newborn appear during the neonatal period or early childhood. Therefore, an early diagnosis is crucial to prevent the development [...] Read more.

Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications with potential adverse outcomes for mothers and newborns. Its effects on the newborn appear during the neonatal period or early childhood. Therefore, an early diagnosis is crucial to prevent the development of chronic diseases later in adult life. In this study, the urinary metabolome of babies born to GDM mothers was characterized. In total, 144 neonatal and maternal (second and third trimesters of pregnancy) urinary samples were analyzed using targeted metabolomics, combining liquid chromatographic mass spectrometry (LC-MS/MS) and flow injection analysis mass spectrometry (FIA-MS/MS) techniques. We provide here the neonatal urinary concentration values of 101 metabolites for 26 newborns born to GDM mothers and 22 newborns born to healthy mothers. The univariate analysis of these metabolites revealed statistical differences in 11 metabolites. Multivariate analyses revealed a differential metabolic profile in newborns of GDM mothers characterized by dysregulation of acylcarnitines, amino acids, and polyamine metabolism. Levels of hexadecenoylcarnitine (C16:1) and spermine were also higher in newborns of GDM mothers. The maternal urinary metabolome revealed significant differences in butyric, isobutyric, and uric acid in the second and third trimesters of pregnancy. These metabolic alterations point to the impact of GDM in the neonatal period. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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16 pages, 4269 KiB

Open AccessArticle

Application of Thin-Film Microextraction to Analyze Volatile Metabolites in A549 Cancer Cells

by Wojciech Filipiak, Karol Jaroch, Paulina Szeliska, Karolina Żuchowska and Barbara Bojko

Metabolites 2021, 11(10), 704; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11100704 - 14 Oct 2021

Cited by 7 | Viewed by 2193

Abstract

Volatile organic compounds (VOCs) have been proposed in the last two decades as biomarkers for disease detection and therapeutic monitoring. Model in vitro experiments with established cell lines are fundamental to clarify whether given VOCs originate from normal human cells or pathogens, including [...] Read more.

Volatile organic compounds (VOCs) have been proposed in the last two decades as biomarkers for disease detection and therapeutic monitoring. Model in vitro experiments with established cell lines are fundamental to clarify whether given VOCs originate from normal human cells or pathogens, including transformed cancer cells. Due to the trace concentrations of target metabolites, adsorptive enrichment is needed before gas chromatography-mass spectrometry (GC-MS) analysis, with solid-phase microextraction (SPME) being perfectly suited for this purpose. Here, a modification of SPME, the thin-film microextraction (TFME) technique, is proposed for analysis of cellular VOCs, which utilizes a planar mesh coated with stationary phase to increase the extraction phase volume and active surface area. In this study, four different adsorbents were compared: carboxen, divinylbenzene, hydrophobic−lipophilic balanced and polydimethylsiloxane. Amongst them, HLB sheets using poly(divinylbenzene-co-N-vinyl-pyrrolidone) skeleton structure proved to be the most versatile, enabling the most sensitive analysis of VOCs with a broad polarity and volatility. For HLB, sampling type (internal static headspace, external bi-directional headspace), extraction temperature and extraction time were also examined. An established method was successfully applied to analyze metabolites produced by A549 cells revealing five volatiles at significantly higher (additionally benzaldehyde at lower) levels in cell culture medium compared to the cell-free reference medium headspace. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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13 pages, 1552 KiB

Open AccessArticle

Enhanced Access to the Health-Related Skin Metabolome by Fast, Reproducible and Non-Invasive WET PREP Sampling

by Jamie Afghani, Claudia Huelpuesch, Philippe Schmitt-Kopplin, Claudia Traidl-Hoffmann, Matthias Reiger and Constanze Mueller

Metabolites 2021, 11(7), 415; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11070415 - 24 Jun 2021

Cited by 6 | Viewed by 2708

Abstract

Our skin influences our physical and mental health, and its chemical composition can reflect environmental and disease conditions. Therefore, through sampling the skin metabolome, we can provide a promising window into the mechanisms of the body. However, the broad application of skin metabolomics [...] Read more.

Our skin influences our physical and mental health, and its chemical composition can reflect environmental and disease conditions. Therefore, through sampling the skin metabolome, we can provide a promising window into the mechanisms of the body. However, the broad application of skin metabolomics has recently been hampered by a lack of easy and widely applicable sampling methods. Here, we present a novel rapid, simple, and, most importantly, painless and non-invasive sampling technique suitable for clinical studies of fragile or weakened skin. The method is called WET PREP and is simply a lavage of the skin which focuses on capturing the metabolome. We systematically evaluate WET PREPs in comparison with the non-invasive method of choice in skin metabolomics, swab collection, using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS²) on two complementary chromatographic columns (C18 reversed phase and hydrophilic interaction chromatography). We also integrate targeted analyses of key metabolites of skin relevance. Overall, WET PREP provides a strikingly more stable shared metabolome across sampled individuals, while also being able to capture unique individual metabolites with a high consistency in intra-individual reproducibility. With the exception of (phospho-)lipidomic studies, we recommend WET PREPs as the preferred skin metabolome sampling technique due to the quick preparation time, low cost, and gentleness for the patient. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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12 pages, 3653 KiB

Open AccessArticle

Identification of Salivary Microorganisms and Metabolites Associated with Halitosis

by Jae-kwon Jo, Seung-Ho Seo, Seong-Eun Park, Hyun-Woo Kim, Eun-Ju Kim, Chang-Su Na, Kwang-Moon Cho, Sun-Jae Kwon, Young-Ho Moon and Hong-Seok Son

Metabolites 2021, 11(6), 362; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11060362 - 07 Jun 2021

Cited by 13 | Viewed by 3560

Abstract

Halitosis is mainly caused by the action of oral microbes. The purpose of this study was to investigate the differences in salivary microbes and metabolites between subjects with and without halitosis. Of the 52 participants, 22 were classified into the halitosis group by [...] Read more.

Halitosis is mainly caused by the action of oral microbes. The purpose of this study was to investigate the differences in salivary microbes and metabolites between subjects with and without halitosis. Of the 52 participants, 22 were classified into the halitosis group by the volatile sulfur compound analysis on breath samples. The 16S rRNA gene amplicon sequencing and metabolomics approaches were used to investigate the difference in microbes and metabolites in saliva of the control and halitosis groups. The profiles of microbiota and metabolites were relatively different between the halitosis and control groups. The relative abundances of Prevotella, Alloprevotella, and Megasphaera were significantly higher in the halitosis group. In contrast, the relative abundances of Streptococcus, Rothia, and Haemophilus were considerably higher in the control group. The levels of 5-aminovaleric acid and n-acetylornithine were significantly higher in the halitosis group. The correlation between identified metabolites and microbiota reveals that Alloprevotella and Prevotella might be related to the cadaverine and putrescine pathways that cause halitosis. This study could provide insight into the mechanisms of halitosis. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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12 pages, 1212 KiB

Open AccessArticle

Measurement of Exhaled Nitric Oxide in 456 Lung Cancer Patients Using a Ringdown FENO Analyzer

by Jing Li, Qingyuan Li, Xin Wei, Qing Chen, Meixiu Sun and Yingxin Li

Metabolites 2021, 11(6), 352; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11060352 - 31 May 2021

Cited by 4 | Viewed by 2330

Abstract

The objective of this study was to investigate the clinical value of exhaled nitric oxide (NO) for diagnosing lung cancer patients by using a relatively large sample. An online and near-real-time ringdown exhaled NO analyzer calibrated by an electrochemical sensor at clinical was [...] Read more.

The objective of this study was to investigate the clinical value of exhaled nitric oxide (NO) for diagnosing lung cancer patients by using a relatively large sample. An online and near-real-time ringdown exhaled NO analyzer calibrated by an electrochemical sensor at clinical was used for breath analysis. A total of 740 breath samples from 284 healthy control subjects (H) and 456 lung cancer patients (LC) were collected. The recorded data included exhaled NO, medications taken within the last half month, demographics, fasting status and smoking status. The LC had a significantly higher level of exhaled NO than the H (H: 21.0 ± 12.1 ppb vs. LC: 34.1 ± 17.2 ppb). The area under the receiver operating characteristic curve for exhaled NO predicting LC and H was 0.728 (sensitivity was 0.798; specificity was 0.55). There was no significant difference in exhaled NO level between groups divided by different types of LC, tumor node metastasis (TNM) stage, sex, smoking status, age, body mass index (BMI) or fasting status. Exhaled NO level alone is not a useful clinical tool for identifying lung cancer, but it should be considered when developing a diagnosis model of lung cancer by using breath analysis. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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15 pages, 2446 KiB

Open AccessArticle

Real Time Breath Analysis Using Portable Gas Chromatography for Adult Asthma Phenotypes

by Ruchi Sharma, Wenzhe Zang, Menglian Zhou, Nicole Schafer, Lesa A. Begley, Yvonne J. Huang and Xudong Fan

Metabolites 2021, 11(5), 265; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11050265 - 23 Apr 2021

Cited by 13 | Viewed by 3154

Abstract

Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g., atopy, obesity, inhaled steroid use) may confound interpretation of putative biomarkers and of underlying [...] Read more.

Asthma is heterogeneous but accessible biomarkers to distinguish relevant phenotypes remain lacking, particularly in non-Type 2 (T2)-high asthma. Moreover, common clinical characteristics in both T2-high and T2-low asthma (e.g., atopy, obesity, inhaled steroid use) may confound interpretation of putative biomarkers and of underlying biology. This study aimed to identify volatile organic compounds (VOCs) in exhaled breath that distinguish not only asthmatic and non-asthmatic subjects, but also atopic non-asthmatic controls and also by variables that reflect clinical differences among asthmatic adults. A total of 73 participants (30 asthma, eight atopic non-asthma, and 35 non-asthma/non-atopic subjects) were recruited for this pilot study. A total of 79 breath samples were analyzed in real-time using an automated portable gas chromatography (GC) device developed in-house. GC-mass spectrometry was also used to identify the VOCs in breath. Machine learning, linear discriminant analysis, and principal component analysis were used to identify the biomarkers. Our results show that the portable GC was able to complete breath analysis in 30 min. A set of nine biomarkers distinguished asthma and non-asthma/non-atopic subjects, while sets of two and of four biomarkers, respectively, further distinguished asthmatic from atopic controls, and between atopic and non-atopic controls. Additional unique biomarkers were identified that discriminate subjects by blood eosinophil levels, obese status, inhaled corticosteroid treatment, and also acute upper respiratory illnesses within asthmatic groups. Our work demonstrates that breath VOC profiling can be a clinically accessible tool for asthma diagnosis and phenotyping. A portable GC system is a viable option for rapid assessment in asthma. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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15 pages, 2261 KiB

Open AccessArticle

Exhaled Breath Reflects Prolonged Exercise and Statin Use during a Field Campaign

by Ben Henderson, Guilherme Lopes Batista, Carlo G. Bertinetto, Joris Meurs, Dušan Materić, Coen C. W. G. Bongers, Neeltje A. E. Allard, Thijs M. H. Eijsvogels, Rupert Holzinger, Frans J. M. Harren, Jeroen J. Jansen, Maria T. E. Hopman and Simona M. Cristescu

Metabolites 2021, 11(4), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11040192 - 24 Mar 2021

Cited by 8 | Viewed by 3106

Abstract

Volatile organic compounds (VOCs) in exhaled breath provide insights into various metabolic processes and can be used to monitor physiological response to exercise and medication. We integrated and validated in situ a sampling and analysis protocol using proton transfer reaction time-of-flight mass spectrometry [...] Read more.

Volatile organic compounds (VOCs) in exhaled breath provide insights into various metabolic processes and can be used to monitor physiological response to exercise and medication. We integrated and validated in situ a sampling and analysis protocol using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) for exhaled breath research. The approach was demonstrated on a participant cohort comprising users of the cholesterol-lowering drug statins and non-statin users during a field campaign of three days of prolonged and repeated exercise, with no restrictions on food or drink consumption. The effect of prolonged exercise was reflected in the exhaled breath of participants, and relevant VOCs were identified. Most of the VOCs, such as acetone, showed an increase in concentration after the first day of walking and subsequent decrease towards baseline levels prior to walking on the second day. A cluster of short-chain fatty acids including acetic acid, butanoic acid, and propionic acid were identified in exhaled breath as potential indicators of gut microbiota activity relating to exercise and drug use. We have provided novel information regarding the use of breathomics for non-invasive monitoring of changes in human metabolism and especially for the gut microbiome activity in relation to exercise and the use of medication, such as statins. Full article

(This article belongs to the Special Issue Non-Invasive Monitoring of Human Metabolism)

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