Diagnostic Value of Concentration Profiles of Glucocorticosteroids and Endocannabinoids in Hair

Background:Endogenous corticosteroids and endocannabinoids are both known to be involved in stress adaption and anti-inflammatory and immuneregulatory effects. The application of hair as retrospective specimen for long-term recording of corticosteroids and its association with stress-induced biochemical alterations was intensively examined.Methods:To evaluate the stability and correlation of various parameters of the endocannabinoid and corticosteroid systems, a prospective study was carried out. Hair samples were collected monthly over a pregnancy cycle (sixth week of pregnancy to 9 weeks postpartum). By comparison of hair concentrations in particular segments (ie, grown in the same time span but collected at different times), an examination of analyte stability in hair was achieved. Additionally, the comparison of proximal segments provided on biochemical information that is independent of alteration due to physical instability. The detection limits of a validated procedure using solid-phase extraction cleanup and liquid chromatography-mass spectrometry proved to be suitable to identify the endogenous levels of cortisol (limits of detection = 1.6 pg/mg), cortisone (2.1 pg/mg), anandamide (AEA, 0.3 pg/mg), and 2-arachidonoylglycerol (15 pg/mg).Results:Corticosteroid concentrations in corresponding hair segments were found to be reduced with increasing hair age; an average decline of cortisol and cortisone by 50% in 4 months was estimated. Independently, an increase of cortisol and cortisone in proximal segments collected during pregnancy was confirmed, which is assumed to be stress related. Endocannabinoids proved to be by far more stable, as demonstrated by subsequent monthly collection of corresponding segments and there was hardly any washout of AEA detectable. Elevated hair concentrations of AEA and 2-arachidonoylglycerol were detected in the first-second trimester of pregnancy, which corresponds to negative correlations between AEA, cortisol, and cortisone

Hair Analysis for Determination of Isoniazid Concentrations and Acetylator Phenotype during Antituberculous Treatment

Background. Analysis of isoniazid (INH) uptake has been based on measurement of plasma concentrations providing a short-term and potentially biased view. Objectives. To establish hair analysis as a tool to measure long-term uptake of INH and to assess whether acetylator phenotype in hair reflects N-acetyltransferase-2 (NAT2) genotype. Design and Methods. INH and acetyl-INH concentrations in hair were determined in patients on INH treatment for M. tuberculosis infection using high pressure liquid chromatography/mass spectrometry. Acetyl-INH/INH ratios were correlated with NAT-2 genotype. Results. Hair concentrations of INH, determined in 40 patients, were not dependent on ethnic group or body mass index and were significantly higher in male compared to female patients (median (range) 2.37 ng/mg (0.76–4.9) versus 1.11 ng/mg (0.02–7.20) (P = 0.02). Acetyl-INH/INH ratios were a median of 15.2% (14.5 to 31.7) in homozygous rapid acetylator NAT-2 genotype and 37.3% (1.73 to 51.2) in the heterozygous rapid acetylator NAT-2 genotype and both significantly higher than in the slow acetylator NAT-2 genotype with 5.8% (0.53 to 14.4) (P < 0.05). Conclusions. Results of hair analysis for INH showed lower concentrations in females. Acetyl-INH/INH ratios were significantly lower in patients with slow acetylator versus rapid acetylator genotypes

Identification of human in vitro metabolites of the haemoglobin S polymerization inhibitor voxelotor for doping control purposes

Voxelotor (GBT440) is a haemoglobin S polymerization inhibitor used to treat anaemia in sickle cell disease. Due to an increase of arterial oxygen saturation as well as serum erythropoietin and haemoglobin, the World Anti-Doping Agency included voxelotor in the list of prohibited substances and methods in 2023. The objective of the present study was to identify and characterize metabolites of voxelotor to detect a potential misuse by athletes. The biotransformation was studied in vitro using the human hepatocellular cell line HepG2 and pooled human liver microsomes. The metabolites were analysed using high-performance liquid chromatography (high-resolution) mass spectrometry. In total, three phase I metabolites and six phase II metabolites (resulting from glucuro-conjugation and O-methylation) were formed by the HepG2 cells in a time-dependent manner, and two phase I metabolites were generated by the liver microsomes, among them one also found in the HepG2 incubations. A reduced metabolite and the glucuro-conjugate of a reduced metabolite were the most abundant formed by HepG2 cells. In addition, metabolites resulting from mono-hydroxylation, reduction and O-methylation in different combinations were identified. Voxelotor was also found as glucuro-conjugate with a low abundance. With the spectrometric behaviour of voxelotor and its in vitro metabolites described herein, an implementation in doping control screening and, consequently, a detection of an abuse in an athlete urine sample might be possible

Motion sickness, stress and the endocannabinoid system

A substantial number of individuals are at risk for the development of motion sickness induced nausea and vomiting (N&V) during road, air or sea travel. Motion sickness can be extremely stressful but the neurobiologic mechanisms leading to motion sickness are not clear. The endocannabinoid system (ECS) represents an important neuromodulator of stress and N&V. Inhibitory effects of the ECS on N&V are mediated by endocannabinoid-receptor activation

Corrigendum: Deposition of an active substance on upper and lower leaf surface and implications on the efficacy in different ornamental plants depending on nozzle type and addition of a wetting-agent

Der ursprüngliche Artikel wurde am 01.02.2021 im Journal für Kulturpflanzen 73 (1-2), 9-20, https://doi.org/10.5073/JfK.2021.01-02.01 publiziert.Der Artikel enthält eine fehlerhafte Abbildung (Abb. 7), deren rechte Teilabbildung versehentlich ein Duplikat der linken Teilabbildung ist. Die korrigierte Abb. 7 erscheint hier als Abb. .Die Schlussfolgerungen des Artikels bleiben unverändert. Wir entschuldigen uns für diesen Fehler.The original article was published on 1 February 2021in Journal of Cultivated Plants 73 (1-2), 9-20, https://doi.org/10.5073/JfK.2021.01-02.01.The article contains errors in Fig. 7, whose left part was duplicated, accidentally. The corrected Fig. 7 appears here as Fig. .The conclusions of the article remain unchanged. We apologize for the error

Deposition of an active substance on upper and lower leaf surface and implications on the efficacy in different ornamental plants depending on nozzle type and addition of a wetting-agent

Die Verteilung eines Pflanzenschutzmittels im Pflanzenbestand ist ganz wesentlich von der Verfügbarkeit und Verwendung einer geeigneten Applikationstechnik abhängig. Nur eine gute Verteilung gewährleistet den sicheren Kontakt der Zielorganismen mit dem Wirkstoff. Das gilt insbesondere für Schädlinge die sich auf der Blattunterseite aufhalten. Die Auswirkung des Düsentyps sowie die Verwendung eines Netzmittels auf die Wirkstoffanlagerung an die Blattober- und -unterseite und die resultierende Wirksamkeit sind Gegenstand dieser Untersuchungen.Für die Ermittlung der Wirkstoffanlagerung wurde ein künstliches Blatt eingesetzt, bei dem die daran befestigten Glasfaserfilter als Blattober- bzw. -unterseite getrennt analysiert werden konnten. Die Verwendung einer Hohlkegeldüse erhöhte im Vergleich zu einer Flachstrahldüse die Anlagerung auf der Oberseite der künstlichen Blätter in schmalblättrigen Brachyscome multifida. Die Doppelflachstrahldüse unterschied sich nicht von den anderen Düsentypen. In breitblättrigen Pelargonium-Zonale-Hybriden und Fuchsia-Hybriden wurden keine Unterschiede zwischen den Düsentypen festgestellt. Die Wirkstoffanlagerung auf der Blattunterseite der künstlichen Blätter an der Fuchsia-Hybride und die Wirksamkeit auf Trialeurodes vaporariorum war unabhängig vom Düsentyp gering.The distribution of a plant protection product in the plant stand depends to a large extent on the availability and use of a suitable application technique. Only a good distribution guarantees the safe contact of the target organisms with the active ingredient. This applies in particular to pests which are on the underside of the leaves. The effect of the nozzle type as well as the use of a wetting agent on the active ingredient attachment to the upper and lower leaf surface and the resulting effectiveness are the subject of these investigations.For the determination of the active ingredient attachment an artificial leaf was used, in which the glass fiber filters attached to it could be analyzed separately as the upper and lower side of the leaf. The use of a hollow cone nozzle, as compared to the flat spray nozzle, increased the attachment on the upper side of the artificial leaves in narrow-leaved Brachyscome multifida. The double flat fan nozzle did not differ significantly to the other nozzle types. In broad-leaved Pelargonium-zonale-hybrids and Fuchsia hybrids no differences were found between nozzle types. The active ingredient attachment on the underside of the artificial leaves on the Fuchsia hybrid and the efficacy on Trialeurodes vapora­riorum was low regardless of the nozzle type

Stress Related Shift Toward Inflammaging in Cosmonauts After Long-Duration Space Flight

Space flight exerts a specific conglomerate of stressors on humans that can modulate the immune system. The mechanism remains to be elucidated and the consequences for cosmonauts in the long term are unclear. Most of the current research stems from short-term spaceflights as well as pre- and post-flight analyses due to operational limitations. Immune function of 12 cosmonauts participating in a long-duration (&gt;140 days) spaceflight mission was monitored pre-, post-, and on two time-points in-flight. While the classical markers for stress such as cortisol in saliva where not significantly altered, blood concentrations of the endocannabinoid system (ECS) were found to be highly increased in-flight indicating a biological stress response. Moreover, subjects showed a significant rise in white blood cell counts. Neutrophils, monocytes and B cells increased by 50% whereas NK cells dropped by nearly 60% shortly after landing. Analysis of blood smears showed that lymphocyte percentages, though unchanged pre- and post-flight were elevated in-flight. Functional tests on the ground revealed stable cellular glutathione levels, unaltered baseline and stimulated ROS release in neutrophils but an increased shedding of L-selectin post-flight. In vitro stimulation of whole blood samples with fungal antigen showed a highly amplified TNF and IL-1β response. Furthermore, a significant reduction in CD4+CD25+CD27low regulatory T cells was observed post-flight but returned to normal levels after one month. Concomitantly, high in-flight levels of regulatory cytokines TGF-β, IL-10 and IL-1ra dropped rapidly after return to Earth. Finally, we observed a shift in the CD8+ T cell repertoire toward CD8+ memory cells that lasted even one month after return to Earth.Conclusion: Long-duration spaceflight triggered a sustained stress dependent release of endocannabinoids combined with an aberrant immune activation mimicking features of people at risk for inflammation related diseases. These effects persisted in part 30 days after return to Earth. The currently available repertoire of in-flight testing as well as the post-flight observation periods need to be expanded to tackle the underlying mechanism for and consequences of these immune changes in order to develop corresponding mitigation strategies based on a personalized approach for future interplanetary space explorations

Modulations of Neuroendocrine Stress Responses During Confinement in Antarctica and the Role of Hypobaric Hypoxia

The Antarctic continent is an environment of extreme conditions. Only few research stations exist that are occupied throughout the year. The German station Neumayer III and the French-Italian Concordia station are such research platforms and human outposts. The seasonal shifts of complete daylight (summer) to complete darkness (winter) as well as massive changes in outside temperatures (down to -80 degrees C at Concordia) during winter result in complete confinement of the crews from the outside world. In addition, the crew at Concordia is subjected to hypobaric hypoxia of similar to 650 hPa as the station is situated at high altitude (3,233 m). We studied three expedition crews at Neumayer Ill (sea level) (n = 16) and two at Concordia (high altitude) (n = 15) to determine the effects of hypobaric hypoxia on hormonal/metabolic stress parameters [endocannabinoids (ECs), catecholamines, and glucocorticoids] and evaluated the psychological stress over a period of 11 months including winter confinement. In the Neumayer III (sea level) crew, EC and n-acylethanolamide (NAE) concentrations increased significantly already at the beginning of the deployment (p < 0.001) whereas catecholamines and cortisol remained unaffected. Over the year, ECs and NAEs stayed elevated and fluctuated before slowly decreasing till the end of the deployment. The classical stress hormones showed small increases in the last third of deployment. By contrast, at Concordia (high altitude), norepinephrine concentrations increased significantly at the beginning (p < 0.001) which was paralleled by low EC levels. Prior to the second half of deployment, norepinephrine declined constantly to end on a low plateau level, whereas then the EC concentrations increased significantly in this second period during the overwintering (p < 0.001). Psychometric data showed no significant changes in the crews at either station. These findings demonstrate that exposition of healthy humans to the physically challenging extreme environment of Antarctica (i) has a distinct modulating effect on stress responses. Additionally, (ii) acute high altitude/hypobaric hypoxia at the beginning seem to trigger catecholamine release that downregulates the EC response. These results (iii) are not associated with psychological stress

Using response-time latencies to measure athletes’ doping attitudes : the brief implicit attitude test identifies substance abuse in bodybuilders

Knowing and, if necessary, altering competitive athletes' real attitudes towards the use of banned performance-enhancing substances is an important goal of worldwide doping prevention efforts. However athletes will not always be willing to reporting their real opinions. Reaction time-based attitude tests help conceal the ultimate goal of measurement from the participant and impede strategic answering. This study investigated how well a reaction time-based attitude test discriminated between athletes who were doping and those who were not. We investigated whether athletes whose urine samples were positive for at least one banned substance (dopers) evaluated doping more favorably than clean athletes (non-dopers).publishe

Verteilung von Acetamiprid in Rosen nach SpritzapplikationPoster + Abstract

Distribution of acetamiprid in roses after spray applicationPoster + Abstrac