729 research outputs found
Abuse of nutmeg seeds: Detectable by means of liquid chromatography-mass spectrometry techniques?
Numerous case reports of intoxications with nutmeg seeds (Myristica fragrans, Houtt.)
can be found in literature often following their abuse, as psychotropic effects were
described after ingestions of large doses. The successful detection of the main ingredients of the nutmeg seeds essential oil elemicin, myristicin, and safrole, as well as
their metabolites in human urine by gas chromatography coupled to mass spectrometry (GC-MS) was already described. The aim of this study was to investigate the
detectability of the main ingredients of nutmeg seeds and their metabolites in human
blood and urine samples using liquid chromatography coupled to linear ion trap mass
spectrometry (LC-LIT-MSn
) and liquid chromatography coupled to high-resolution
mass spectrometry (LC-HRMS/MS) after nutmeg seed abuse. Sample material of
three individuals was retrospectively investigated after a systematic screening
approach indicated an intoxication with nutmeg seeds as a likely cause of symptoms.
Metabolic patterns in plasma and urine using GC-MS were comparable with those
described in earlier publications. Investigations using hyphenated liquid chromatography techniques lead to the detection of myristicin and safrole, as well as further
metabolites not described using GC-MS and revealed sulfation as an additional Phase
II metabolic pathway. These results might help to detect or confirm future intoxications with nutmeg seeds by using LC-MS techniques
Further development of a liquid chromatography-high-resolution mass spectrometry/mass spectrometry-based strategy for analyzing eight biomarkers in human urine indicating toxic mushroom or Ricinus communis ingestions
Recently, we presented a strategy for analysis of eight biomarkers in human urine to verify toxic mushroom or Ricinus communis ingestions. However, screening for the full panel is not always necessary. Thus, we aimed to develop a strategy to reduce analysis time and by focusing on two sets of analytes. One set (A) for biomarkers of late-onset syndromes, such as phalloides syndrome or the syndrome after castor bean intake. Another set (B) for biomarkers of early-onset syndromes, such as pantherine–muscaria syndrome and muscarine syndrome. Both analyses should be based on hydrophilic-interaction liquid chromatography coupled with high-resolution mass spectrometry (MS)/MS (HILIC-HRMS/MS). For A, urine samples were prepared by liquid–liquid extraction using dichloromethane and subsequent solid-phase extraction of the aqueous supernatant. For B urine was precipitated using acetonitrile. Method A was validated for ricinine and α- and β-amanitin and method B for muscarine, muscimol, and ibotenic acid according to the specifications for qualitative analytical methods. In addition, robustness of recovery and normalized matrix factors to matrix variability measured by urinary creatinine was tested. Moreover, applicability was tested using 10 urine samples from patients after suspected mushroom intoxication. The analytes α- and β-amanitin, muscarine, muscimol, and ibotenic acid could be successfully identified. Finally, psilocin-O-glucuronide could be identified in two samples and unambiguously distinguished from bufotenine-O-glucuronide via their MS2 patterns. In summary, the current workflow offers several advantages towards the previous method, particularly being more labor-, time-, and cost-efficient, more robust, and more sensitive
Analysis of α- and β-amanitin in Human Plasma at Subnanogram per Milliliter Levels by Reversed Phase Ultra-High Performance Liquid Chromatography Coupled to Orbitrap Mass Spectrometry
Amatoxins are known to be one of the main causes of serious to fatal mushroom intoxication. Thorough treatment, analytical confirmation, or exclusion of amatoxin intake is crucial in the case of any suspected mushroom poisoning. Urine is often the preferred matrix due to its higher concentrations compared to other body fluids. If urine is not available, analysis of human blood plasma is a valuable alternative for assessing the severity of intoxications. The aim of this study was to develop and validate a liquid chromatography (LC)-high resolution tandem mass spectrometry (HRMS/MS) method for confirmation and quantitation of α- and β-amanitin in human plasma at subnanogram per milliliter levels. Plasma samples of humans after suspected intake of amatoxin-containing mushrooms should be analyzed and amounts of toxins compared with already published data as well as with matched urine samples. Sample preparation consisted of protein precipitation, aqueous liquid-liquid extraction, and solid-phase extraction. Full chromatographical separation of analytes was achieved using reversed-phase chromatography. Orbitrap-based MS allowed for sufficiently sensitive identification and quantification. Validation was successfully carried out, including analytical selectivity, carry-over, matrix effects, accuracy, precision, and dilution integrity. Limits of identification were 20 pg/mL and calibration ranged from 20 pg/mL to 2000 pg/mL. The method was applied to analyze nine human plasma samples that were submitted along with urine samples tested positive for amatoxins. α-Amanitin could be identified in each plasma sample at a range from 37–2890 pg/mL, and β-amanitin was found in seven plasma samples ranging from <20–7520 pg/mL. A LC-HRMS/MS method for the quantitation of amatoxins in human blood plasma at subnanogram per milliliter levels was developed, validated, and used for the analysis of plasma samples. The method provides a valuable alternative to urine analysis, allowing thorough patient treatment but also further study the toxicokinetics of amatoxins
Nominal or Real? The Impact of Regional Price Levels on Satisfaction with Life
According to economic theory, real income, i.e., nominal income adjusted for purchasing power, should be the relevant source of life satisfaction. Previous work, however, has only studied the impact of inflation adjusted nominal income and not taken into account regional differences in purchasing power. Therefore, we use a novel data set to study how regional price levels affect satisfaction with life. The data set comprises about 7 million data points that are used to construct a price level for each of the 428 administrative districts in Germany. We estimate pooled OLS and ordered probit models that include a comprehensive set of individual level, time-varying and time-invariant control variables as well as control variables that capture district heterogeneity other than the price level. Our results show that higher price levels significantly reduce life satisfaction. Furthermore, we find that a higher price level tends to induce a larger loss in life satisfaction than a corresponding decrease in nominal income. A formal test of neutrality of money, however, does not reject neutrality of money. Our results provide an argument in favor of regional indexation of government transfer payments such as social welfare benefits
The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network
Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientÅ› delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects
Analytical expressions for stopping-power ratios relevant for accurate dosimetry in particle therapy
In particle therapy, knowledge of the stopping-power ratios (STPRs) of the
ion beam for air and water is necessary for accurate ionization chamber
dosimetry. Earlier work has investigated the STPRs for pristine carbon ion
beams, but here we expand the calculations to a range of ions (1 <= z <= 18) as
well as spread out Bragg peaks (SOBPs) and provide a theoretical in-depth study
with a special focus on the parameter regime relevant for particle therapy. The
Monte Carlo transport code SHIELD-HIT is used to calculate complete
particle-fluence spectra which are required for determining STPRs according to
the recommendations of the International Atomic Energy Agency (IAEA).
We confirm that the STPR depends primarily on the current energy of the ions
rather than on their charge z or absolute position in the medium. However,
STPRs for different sets of stopping-power data for water and air recommended
by the International Commission on Radiation Units & Measurements (ICRU) are
compared, including also the recently revised data for water, yielding
deviations up to 2% in the plateau region. In comparison, the influence of the
secondary particle spectra on the STPR is about two orders of magnitude smaller
in the whole region up till the practical range. The gained insights enable us
to propose an analytic approximation for the STPR for both pristine and SOBPs
as a function of penetration depth, which parametrically depend only on the
initial energy and the residual range of the ion, respectively.Comment: 21 pages, 5 figures, fixed bug with figures in v
Conversion of self-assembled monolayers into nanocrystalline graphene: Structure and electric transport
Graphene-based materials have been suggested for applications ranging from
nanoelectronics to nanobiotechnology. However, the realization of
graphene-based technologies will require large quantities of free-standing
two-dimensional (2D) carbon materials with tuneable physical and chemical
properties. Bottom-up approaches via molecular self-assembly have great
potential to fulfil this demand. Here, we report on the fabrication and
characterization of graphene made by electron-radiation induced cross-linking
of aromatic self-assembled monolayers (SAMs) and their subsequent annealing. In
this process, the SAM is converted into a nanocrystalline graphene sheet with
well defined thickness and arbitrary dimensions. Electric transport data
demonstrate that this transformation is accompanied by an insulator to metal
transition that can be utilized to control electrical properties such as
conductivity, electron mobility and ambipolar electric field effect of the
fabricated graphene sheets. The suggested route opens broad prospects towards
the engineering of free-standing 2D carbon materials with tuneable properties
on various solid substrates and on holey substrates as suspended membranes.Comment: 30 pages, 5 figure
An intercomparison study of four different techniques for measuring the chemical composition of nanoparticles
Currently, the complete chemical characterization of nanoparticles (< 100 nm) represents an analytical challenge, since these particles are abundant in number but have negligible mass. Several methods for particle-phase characterization have been recently developed to better detect and infer more accurately the sources and fates of sub-100 nm particles, but a detailed comparison of different approaches is missing. Here we report on the chemical composition of secondary organic aerosol (SOA) nanoparticles from experimental studies of α-pinene ozonolysis at −50, −30, and −10 ∘C and intercompare the results measured by different techniques. The experiments were performed at the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). The chemical composition was measured simultaneously by four different techniques: (1) thermal desorption–differential mobility analyzer (TD–DMA) coupled to a NO chemical ionization–atmospheric-pressure-interface–time-of-flight (CI–APi–TOF) mass spectrometer, (2) filter inlet for gases and aerosols (FIGAERO) coupled to an I high-resolution time-of-flight chemical ionization mass spectrometer (HRToF-CIMS), (3) extractive electrospray Na ionization time-of-flight mass spectrometer (EESI-TOF), and (4) offline analysis of filters (FILTER) using ultra-high-performance liquid chromatography (UHPLC) and heated electrospray ionization (HESI) coupled to an Orbitrap high-resolution mass spectrometer (HRMS). Intercomparison was performed by contrasting the observed chemical composition as a function of oxidation state and carbon number, by estimating the volatility and comparing the fraction of volatility classes, and by comparing the thermal desorption behavior (for the thermal desorption techniques: TD–DMA and FIGAERO) and performing positive matrix factorization (PMF) analysis for the thermograms. We found that the methods generally agree on the most important compounds that are found in the nanoparticles. However, they do see different parts of the organic spectrum. We suggest potential explanations for these differences: thermal decomposition, aging, sampling artifacts, etc. We applied PMF analysis and found insights of thermal decomposition in the TD–DMA and the FIGAERO
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High Gas-Phase Methanesulfonic Acid Production in the OH-Initiated Oxidation of Dimethyl Sulfide at Low Temperatures
Dimethyl sulfide (DMS) influences climate via cloud condensation nuclei (CCN) formation resulting from its oxidation products (mainly methanesulfonic acid, MSA, and sulfuric acid, H2SO4). Despite their importance, accurate prediction of MSA and H2SO4from DMS oxidation remains challenging. With comprehensive experiments carried out in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at CERN, we show that decreasing the temperature from +25 to -10 °C enhances the gas-phase MSA production by an order of magnitude from OH-initiated DMS oxidation, while H2SO4production is modestly affected. This leads to a gas-phase H2SO4-to-MSA ratio (H2SO4/MSA) smaller than one at low temperatures, consistent with field observations in polar regions. With an updated DMS oxidation mechanism, we find that methanesulfinic acid, CH3S(O)OH, MSIA, forms large amounts of MSA. Overall, our results reveal that MSA yields are a factor of 2-10 higher than those predicted by the widely used Master Chemical Mechanism (MCMv3.3.1), and the NOxeffect is less significant than that of temperature. Our updated mechanism explains the high MSA production rates observed in field observations, especially at low temperatures, thus, substantiating the greater importance of MSA in the natural sulfur cycle and natural CCN formation. Our mechanism will improve the interpretation of present-day and historical gas-phase H2SO4/MSA measurements
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