283 research outputs found
Overcoming biosampling issues in sport drug testing: anabolic steroids in dried urines
No full textPB12. OVERCOMING BIOSAMPLING ISSUES IN SPORT DRUG TESTING: ANABOLIC STEROIDS IN DRIED URINES
Michele PROTTI,1 Maria Carmen CATAPANO,1 Angelo E. SBERNA,2
Stefano GIROTTI,1 James RUDGE,3 and Laura MERCOLINI1
1Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy
2 Sport Medicine, Enna Local Health Unit, Viale A. Diaz 7, 94100 Enna, Italy
3 Neoteryx LLC, 421 Amapola Avenue, 90501 Torrance, CA, USA
Some crucial points are still under evaluation in the field of sampling and analysis for sport drug testing, including some limitations related to the biological fluid of choice: urine.
Dried matrix (DM) collection is a very promising tool for improving anti-doping analysis, addressing those issues related to frequent and impromptu sampling, detection of substance concentrations, enhanced compound stability and need for rapid and high-throughput protocols. Ongoing innovations have demonstrated DM reliability, which is now directly applicable with the coupling to a wealth of microsampling techniques. This research involves in particular the use of dried urine spots (DUS) and volumetric absorptive microsampling (VAMS) on urines, for the collection of accurate volumes, followed by the LC-MS analysis of the main classes of the substances included in the World Anti-Doping Agency (WADA) prohibited list [1], with particular focus on compounds belonging to the class of anabolic steroids (testosterone, epitestosterone, dihydrotestosterone, androstenedione, methandrostenolone, mesterolone, nandrolone, norethandrolone and danazol.
The goal of this project is to establish and validate simple but reliable protocols for the collection of urine microvolumes, unlikely to be tampered but transportable and, above all, storable with no precautions, to perform screening tests and targeted analysis according to the International Standard for Testing and Investigations (ISTI) and the International Standard for Laboratories (ISL), as part of the World Anti-Doping Code. These protocols would substantially reduce overall analysis costs, allowing their application not only to elite athletes, but also to amateurs in local laboratories.
[1] “The World Anti-Doping Code: the 2016 Prohibited List”. World Anti-Doping Agency (WADA
Variations in central venous pressure during spontaneous breathing well correlate with changes in esophageal pressure
No full textIntroduction: Spontaneously breathing critically ill patients often make strong inspiratory efforts. These respiratory activity can damage lungs, require supranormal work of breathing and produce
alterations in venous return. Clinical exam is not sufficient to determine when the effort is excessive. Strong inspiratory efforts generate falls in pleural pressure, which is difficult to
measure directly but is well estimated by variations in esophageal pressure.1 Unfortunately intraesophageal balloon isn’t available in lots of intensive care units.
Aim of this study was to investigate whether variations in central venous pressure (ΔCVP) adequately reflect respiratory changes in pleural pressure as assessed by changes in esophageal
pressure (ΔPES).
Materials and Methods: We studied spontaneous breathing patients, admitted to our intensive care unit to acute respiratory failure who had a central venous catheter and esophageal balloon.
We compared ΔCVP to ΔPES during zero end expiratory pressure (ZEEP) and during continuous positive airway pressure (CPAP) by Bland–Altman and regression analysis.
Results: We enrolled 5 patients from whom we obtained 5 contemporary measurement of ΔCVP and ΔPES during ZEEP and 5 during CPAP. The average inspiratory ΔPES was 21,08 ± 9,38
cmH2O, and average ΔCVP was 20,90 ± 9,32 cmH2O. In both conditions ΔCVP gave a good estimate of ΔPES (bias = 0.18 cmH2O, limits of agreement +2.49 and –2.14 cmH2O; R2 = 0,984).
Conclusions: ΔCVP gives a good estimate of changes in PES (a surrogate of pleural pressure) during spontaneous inspiratory efforts
Dyedauxiliary groups, an emerging approach in organic chemistry. The case of arylazo sulfones.
No full textNew Trends in the Analysis of Cannabis-Based Products
No full textAs one of the first plants to be cultivated by humans, probably since at least 8000–5000 bce, hemp (Cannabis sativa L.) has been for millennia a source of textile, building, writing and food/feed materials, as well as being used for religious and recreational purposes. Only in relatively recent times has this plant been considered in a mostly negative light by state authorities; probably the first documented legislation restricting cannabis was passed in Arabia in the 1300s ce. More recently, international restrictions to cannabis trade were first applied in 1925 (International Opium Convention), but hemp cultivation mainly for fibre use continued both in Europe and in the United States until at least World War II, and primarily for recreational use in several Asian countries. Severe restrictions on cultivation have been applied at least since 1961 (Single Convention on Narcotic Drugs), and widely diffused with the “War on Drugs” in the United States during the 1970s and 1980s. However, since the 1970s, several countries started making hemp cultivation and use easier, both for fibre and recreational purposes. Since then, restricting legislation has been relaxed in several parts of the world, and medical uses for cannabis products have also been found, finding widespread application in the last ten years. Currently, great emphasis is being put on the difference between “fibre-type” (or “hemp-type”) and “marijuana-type” cannabis. The main difference between the two types resides in the different contents of the two main bioactive compounds: Δ9-tetrahydrocannabinol (THC, Figure 5.1a) and cannabidiol (CBD, Figure 5.1b). The former is considered responsible for the pleasant and recreational psychotropic effects of cannabis, while the latter can have muscle-relaxing and antiemetic properties while being devoid of psychotropic activity. Both are formed in the plant and during recreational use by decarboxylation of the corresponding acids, Δ9-tetrahydrocannabinolic acid (THCA; Figure 5.1c) and cannabidiolic acid (CBDA, Figure 5.1d). The United Nations Office on Drugs and Crime (UNODC) (Drugs 2009) and the American Herbal Pharmacopoeia (2013) define hemp-type cannabis as having a “total THC”/“total CBD” ratio (i.e., [THC+THCA]/[CBD+CBDA] ratio) lower than one, marijuana-type cannabis as having a total THC/total CBD ratio higher than one and intermediate cannabis as having a ratio close to one. This renewed interest in traditional and new uses for cannabis also brings with itself the need for suitably accurate and selective analytical methods to certify the quality of hemp products and steer their use according to their detailed composition. In particular, cannabis-derived food and food supplements, beverages, cosmetics and perfumes need to be characterised in detail, since they are intended for relatively widespread use without any recreational overtones. As a consequence, the situation is being reflected in increased interest from the scientific community. Reviews of new trends for the chemical characterisation of natural cannabis products (Leghissa et al. 2018) (Citti et al. 2020) have recently underscored a lack of scientifically reliable data. Among the causes of this situation, which starkly contrasts with the human use of the cannabis plant since time immemorial, restricting legislation (especially in the United States) is cited. Judging from the relative wealth and diversity of new publications in this field, however, the scientific situation seems to be gradually improving. In this chapter, only methods published in the last five years (2016–February 2021) are reported and described
Simultaneous Photografting of Two Organic Groups on a Gold Surface by using Arylazo Sulfones As the Single Precursors
No full textAutomated One-pot Library Synthesis with Aldehydes as Radical Precursors
No full textThe increased demand for the synthesis of Csp3 enriched motifs
and the urgency of discovering new drugs requires the
development of more efficient technologies and synthetic tools
to accelerate drug discovery processes. Herein, we report a fully
automated strategy for the addition of Csp3 enriched building
blocks onto olefins via Giese addition to forge Csp3-Csp3 bonds.
The developed fully automated protocol allowed the in-situ
conversion of aldehydes (non-redox-active species) to electroactive
imidazolidines and their use as precursors of C-centered
radicals under photoredox catalyzed conditions for the synthesis
of building blocks and bioactive compound libraries by
synthesizing sp3-enriched compounds
Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle
No full textOBJECTIVE: Mitochondrial dysfunction, particularly affecting complex I of the respiratory chain, could play a fundamental role in the development of multiple organ failure during sepsis. Increasing electron flow through complex II by addition of succinate may improve mitochondrial oxygen utilization and thus adenosine triphosphate production. DESIGN: Ex vivo animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS: Fecal peritonitis was induced in conscious, fluid-resuscitated, hemodynamically-monitored rats. Sham-operation and naïve animals acted as controls. At 48 hrs, clinical severity was graded. Soleus muscle was taken for measurement of mitochondrial complex activities and oxygen consumption. The effect of glutamate plus malate (complex I substrates) and succinate (complex II substrate) on mitochondrial respiration was assessed. MEASUREMENTS AND MAIN RESULTS: In the presence of glutamate plus malate, mitochondrial oxygen consumption was abnormally low in skeletal muscle tissue from moderately-to-severely septic animals as compared with naïve and sham-operation controls (both p < .01). On addition of succinate, mitochondrial respiration was augmented in all groups, particularly in moderately-to-severely septic animals (39% ± 6% increase) as compared with naïve (11% ± 5%; p < .01) and sham-operation controls (10% ± 5%; p < .01). In the presence of succinate, mitochondrial oxygen consumption was similar between the groups. CONCLUSIONS: Succinate increases mitochondrial oxygen consumption in ex vivo skeletal muscle taken from septic animals, bypassing the predominant inhibition occurring at complex I. This warrants further exploration in vivo as a putative therapeutic modality
Chromatographic enantioresolution and stereochemical characterization of synthetic cannabinoid receptor agonists with Whelk-O®1 chiral stationary phases under mass spectrometry compatible reversed-phase conditions: A study case with seized samples
No full textSynthetic cannabinoid receptor agonists were enantioseparated with Whelk-O®1 CSPs.
Efficient enantioseparations were obtained under reversed-phase conditions.
The developed HPLC method was compatible to MS detection.
The ICCA concept was useful to appraise the enantiopurity of the studied compounds.
Coupling ECD analysis to in silico simulations allowed to establish the EEO
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