Enhanced-Precision Measurement of Glutathionyl Hemoglobin by MALDI-ToF MS.

Glutathionyl-hemoglobin (HbSSG) is used as a human biomarker to pinpoint systemic oxidative stress caused by various pathological conditions, noxious lifestyles, and exposure to drugs and environmental or workplace toxicants. Measurement by MALDI mass spectrometry is most frequently used, however, the method suffers from excessive uncontrolled variability. This article describes the improvement of a MALDI-ToF mass spectrometry method for HbSSG measurement through enhanced precision, based on strict control of sample preparation steps and spreadsheet-based data analysis.

Differential Redox State and Iron Regulation in Chronic Obstructive Pulmonary Disease, Acute Respiratory Distress Syndrome and Coronavirus Disease 2019.

In patients affected by Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD) and Coronavirus Disease 2019 (COVID-19), unclear mechanisms negatively interfere with the hematopoietic response to hypoxia. Although stimulated by physiological hypoxia, pulmonary hypoxic patients usually develop anemia, which may ultimately complicate the outcome. To characterize this non-adaptive response, we dissected the interplay among the redox state, iron regulation, and inflammation in patients challenged by either acute (ARDS and COVID-19) or chronic (COPD) hypoxia.

High-Throughput Griess Assay of Nitrite and Nitrate in Plasma and Red Blood Cells for Human Physiology Studies under Extreme Conditions.

The metabolism of nitric oxide plays an increasingly interesting role in the physiological response of the human body to extreme environmental conditions, such as underwater, in an extremely cold climate, and at low oxygen concentrations. Field studies need the development of analytical methods to measure nitrite and nitrate in plasma and red blood cells with high requirements of accuracy, precision, and sensitivity. An optimized spectrophotometric Griess method for nitrite-nitrate affords sensitivity in the low millimolar range and precision within ±2 μM for both nitrite and nitrate, requiring 100 μL of scarcely available plasma sample or less than 50 μL of red blood cells.

The Redox Potential of the β--Cysteine Thiol Group in Human Hemoglobin Estimated from In Vitro Oxidant Challenge Experiments.

Glutathionyl hemoglobin is a minor form of hemoglobin with intriguing properties. The measurement of the redox potential of its reactive β--Cysteine is useful to improve understanding of the response of erythrocytes to transient and chronic conditions of oxidative stress, where the level of glutathionyl hemoglobin is increased. An independent literature experiment describes the recovery of human erythrocytes exposed to an oxidant burst by measuring glutathione, glutathione disulfide and glutathionyl hemoglobin in a two-hour period.

Establishing health-based biological exposure limits for pesticides: A proof of principle study using mancozeb.

Pesticides represent an economical, labor-saving, and efficient tool for pest management, but their intrinsic toxic properties may endanger workers and the general population. Risk assessment is necessary, and biological monitoring represents a potentially valuable tool. Several international agencies propose biological exposure indices (BEI), especially for substances which are commonly absorbed through the skin.

Center-of-Mass Energetic Collision-Induced Decomposition in Tandem Triple Quadrupole Mass Spectrometry.

Two scan modes of the triple quadrupole tandem mass spectrometer, namely Collision Induced Dissociation Precursor Ion scan and Neutral Loss scan, allow selectively pinpointing, in a complex mixture, compounds that feature specific chemical groups, which yield characteristic fragment ions or are lost as distinctive neutral fragments. This feature of the triple quadrupole tandem mass spectrometer allows the non-target screening of mixtures for classes of components. The effective (center-of-mass) energy to achieve specific fragmentation depends on the inter-quadrupole voltage (laboratory-frame collision energy) and on the masses of the precursor molecular ion and of the collision gas, through a non-linear relationship.

Discovery of Unexpected Sphingolipids in Almonds and Pistachios with an Innovative Use of Triple Quadrupole Tandem Mass Spectrometry.

The densely packed storage of valuable nutrients (carbohydrates, lipids, proteins, micronutrients) in the endosperm of nuts and seeds makes the study of their complex composition a topic of great importance. Ceramides in the total lipid extract of some ground almonds and pistachios were searched with a systematic innovative discovery precursor ion scan in a triple quadrupole tandem mass spectrometry, where iso-energetic collision activated dissociation was performed. Five descriptors were used to search components with different C18 long chain bases containing different structural motifs (d18:0, d18:1, d18:2, t18:0, t18:1).

LC-MS/MS-Based Profiling of Tryptophan-Related Metabolites in Healthy Plant Foods.

Food plants contain hundreds of bioactive phytochemicals arising from different secondary metabolic pathways. Among these, the metabolic route of the amino acid Tryptophan yields a large number of plant natural products with chemically and pharmacologically diverse properties. We propose the identifier "indolome" to collect all metabolites in the Tryptophan pathway.

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia.

Oxygen (O) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium.

Unambiguous Characterization of -Cresyl Sulfate, a Protein-Bound Uremic Toxin, as Biomarker of Heart and Kidney Disease.

-Cresyl sulfate is one of the bound uremic toxins whose level increases in the sera of patients with the severity of chronic kidney disease and is therefore used as a standard for clinical investigations. Our first attempts to obtain -cresyl sulfate led exclusively to the product of sulfonation of the aromatic ring instead of sulfation on the OH moiety. Nevertheless, this initial discouraging result allowed us to handle both -cresyl sulfate and 2-hydroxy-5-methylbenzenesulfonic acid obtained by different synthetic pathways.

Exposure duration and absorbed dose assessment in pesticide-exposed agricultural workers: Implications for risk assessment and modeling.

Introduction: Absorbed dose assessment from dermal exposure involves multiplying skin contamination by the dermal absorption coefficient, which is usually defined for the standard workday of 8 h. This strategy may suffer from limitations when the duration of exposure is extremely variable, such as in agricultural exposure to pesticides.

Objectives: The aim of this study was to estimate the dose of mancozeb absorbed by agricultural pesticide applicators in a typical working day considering the real duration of exposure, to compare these estimates with those coming from the use of the Fixed Fractional Approach, and to assess the suitability of the dose estimates in the interpretation of biological monitoring results.

Assessment of penconazole exposure in winegrowers using urinary biomarkers.

Penconazole (PEN) is a fungicide used in agriculture. The aim of this work was to evaluate the exposure to PEN in vineyard workers focusing on urinary biomarkers. Twenty-two agricultural workers were involved in the study; they were investigated during PEN applications and re-entry work, performed for 1-4 consecutive working days, for a total of 42 mixing and applications and 12 re-entries.

Correction to: Health risks in international container and bulk cargo transport due to volatile toxic compounds.

[This corrects the article DOI: 10.1186/s12995-015-0059-4.].

Determination of the serine palmitoyl transferase inhibitor myriocin by electrospray and Q-trap mass spectrometry.

Myriocin is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure myriocin in minute specimens of animal tissue. The chemical analog 14-OH-myriocin was used as the internal standard.

Dermal exposure and risk assessment of tebuconazole applicators in vineyards.

Introduction: Models used in the pre-marketing evaluation do not cover all work scenarios and may over- or underestimate exposure.

Objectives: Uncertainties present in the extrapolation from pre-marketing to the post-marketing warrant exposure and risk assessment in real-life working conditions.

Methods: Seven vineyard pesticide applicators were followed for a total of 12 work-days.

Health risks in international container and bulk cargo transport due to volatile toxic compounds.

To ensure the preservation and quality of the goods, physical (i.e. radiation) or chemical pest control is needed.

Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms.

Mercury, cadmium, arsenic and lead are among priority metals for toxicological studies due to the frequent human exposure and to the significant burden of disease following acute and chronic intoxication. Among their common characteristics is chemical affinity to proteins and non-protein thiols and their ability to generate cellular oxidative stress by the best-known Fenton mechanism. Their health effects are however diverse: kidney and liver damage, cancer at specific sites, irreversible neurological damages with metal-specific features.

Biological monitoring of exposure to tebuconazole in winegrowers.

Tebuconazole (TEB) is a fungicide widely used in vineyards and is a suspected teratogen for humans. The aim of this research was to identify urinary biomarkers and the best sampling time for the biological monitoring of exposure to TEB in agricultural workers. Seven vineyard workers of the Monferrato region, Piedemont, Italy, were investigated for a total of 12 workdays.

Toward an "omic" physiopathology of reactive chemicals: thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds.

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g.

A study of the glutathione metaboloma peptides by energy-resolved mass spectrometry as a tool to investigate into the interference of toxic heavy metals with their metabolic processes.

To better understand the fragmentation processes of the metal-biothiol conjugates and their possible significance in biological terms, an energy-resolved mass spectrometric study of the glutathione conjugates of heavy metals, of several thiols and disulfides of the glutathione metaboloma has been carried out. The main fragmentation process of gamma-glutamyl compounds, whether in the thiol, disulfide, thioether or metal-bis-thiolate form, is the loss of the gamma-glutamyl residue, a process which ERMS data showed to be hardly influenced by the sulfur substitution. However, loss of the gamma-glutamyl residue from the mono-S-glutathionyl-mercury (II) cation is a much more energetic process, possibly pointing at a strong coordination of the carboxylic group to the metal.

Electrospray ionization and triple quadrupole tandem mass spectrometry study of some biologically relevant homo- and heterodimeric cadmium thiolate conjugates.

A series of 19 compounds of general formula R1S-Cd-SR2, R1, and R2, being some biologically relevant thiol amino acids and peptides, were prepared by direct reaction of cadmium(II) ions and thiols in water at millimolar concentration. The obtained products were characterized by electrospray ionization and triple quadrupole tandem mass spectrometry. The source spectra of stoichiometric 1:2 Cd-thiol systems containing either an individual thiol or equimolar mixtures of two different thiols featured several Cd-containing signals, although at much lesser intensity than in the previously reported experiments with mercury(II) (J.

Polyurethane foam chips combined with liquid chromatography in the determination of unmetabolized polycyclic aromatic hydrocarbons excreted in human urine.

A method suitable for the determination of unmetabolized polycyclic aromatic hydrocarbons (PAHs) excreted at trace levels (ng/L) in human urine for the monitoring of exposure of the general population to PAH contamination was developed. PAHs were determined, after enrichment by solid-phase extraction on polyurethane foam (PUF) chips, by HPLC with fluorescence detection. Different parameters affecting analyte extraction to the PUF, including urine salting-out and organic additives, and optimization of conditions for clean-up and desorption have been investigated.

Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.

The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses (n=25) and pharmacy technicians (n=5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital (n=12) and in the wards (n=13), and pharmacy technicians prepared the drugs in the central pharmacy.

Assay of urinary alpha-fluoro-beta-alanine by gas chromatography-mass spectrometry for the biological monitoring of occupational exposure to 5-fluorouracil in oncology nurses and pharmacy technicians.

The validation of an analytical method for the measurement of the unnatural amino acid alpha-fluoro-beta-alanine (AFBA), the main metabolite of the antineoplastic drug 5-fluorouracil (5FU), in urine for the biological monitoring of the exposure of hospital workers to the drug when preparing the therapeutical doses and administering to cancer patients is described. The method employed a two-step extractive derivatization of the analyte from urine to the N-trifluoroacety-n-butyl ester derivative and detection by selected-ion monitoring gas chromatography-mass spectrometry of structurally specific fragments. The limit of detection was 20 ng/mL with quantification accuracy better than +/-20% and precision (CV%) better than +/-20% in the range 0.

Volatile organic compounds produced during the aerobic biological processing of municipal solid waste in a pilot plant.

The volatile organic carbon (VOC) and odours emitted during the aerobic biological processing of municipal solid waste (MSW) was studied in a pilot-scale reactor. VOCs were detected by different techniques on solid waste samples and the outlet air stream, before and after a biofilter. Organic compounds (alpha-pinene, beta-myrcene, D-limonene) were also measured in condensate water and leachate from the process.