Mimicking of phase I metabolism reactions of molindone by HLM and photocatalytic methods with the use of UHPLC-MS/MS

Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization

Selected aspects of the radioactive isotopes analytics with particular emphasis on criminal poisonings

Radioactive isotopes and their compounds were used for criminal purposes owing to their convenient chemical and physical properties. They are usually odorless and tasteless and could remain unnoticed. Symptoms are delayed and unspecific, they prevent accurate diagnosis and immediate treatment. Furthermore, radionuclides are hard to detect and analyze due to their radioactive decay that results in conversion into different elements. Radioactive isotope analytics is improved enough to test poisoning nowadays, but also resolve historic mysteries and determine cause of death in homicide cases. In this article we discuss examples of radionuclide intoxication in crime including source, symptoms and diagnostic method. The most known cases of Polonium-210 poisoning in public circulation were discussed. These are poisoning of Alexander Litvinenko and Yasser Arafat in the scientific literature. Despite the similarities in symptoms and death-leading disorders, it was not possible to finally prove the cause of Arafat’s death inherent in the radioactive isotope. This was undoubtedly due to the rather long period that passed from the moment of death to undertaking toxicologically oriented tests. The case of Litvinenko was different and evidence of Polon-210 poisoning can be considered confirmed. Poisoning with iodine-131 isotope, well known for radioactive contamination of the environment after the Chernobyl nuclear power plant failure, is also discussed. The work is supplemented by a review of press reports, in which the motif of criminal poisoning with radioisotopes appears, along with the circumstances that allowed the determination of the direct causes of the crime. It was concluded that despite the rare documented cases of criminal poisoning radioactive isotopes, now the problem is still present. In this aspect, the contribution of the development of toxicological analysis to reducing criminal activities cannot be overestimated. Allowing analysis even years after the crime thanks to the use of modern technology is a factor effectively deterring potential criminals

Analytics of new psychoactive substances (NPS) : in search of optimal solutions

In recent years, new psychoactive substances (NPS) have become a popular alternative to traditional drugs. In the European Union Early Warning System of European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) the number of NPS increases each year. These substances known as legal highs or designer drugs are popular in particular among young people, mostly due to their price and availability. They are usually made in China and then sold in online stores. The variability of these substances and the lack of knowledge of their chemical structure and their metabolic changes pose a great challenge for toxicological analysis. Deaths caused by these drugs are underestimated due to their occurrence as a mixture of multiple drugs, further causing analytical problems. Difficulties in detecting NPS are also noticeable at diagnosis of intoxication, which carries the risk of misinterpretation and improper treatment. Rapid and inexpensive immunoassays used for drug detection have not yet been used in the identification of NPS. This is due to the dynamic changes on the drug market, which make it difficult to create appropriately sensitive and selective screening tests to identify an unknown substance. The production of specific antibodies takes a long time, often exceeding the duration of the presence of the substance in the illicit market. Scientists believe that mass spectrometry-based methods should be used to search for NPS in biological samples because they are sensitive and allow the determination of a specific compound with proper reliability. The use of high-resolution mass spectrometry (HRMS) in the context of screening may be a future strategy and alternative to classic drug tests. Nevertheless, the cost and time-consuming nature of this method currently exclude its use in routine diagnostics. An additional difficulty in carrying out identification is the presence of NPS in body fluids at low concentrations and frequently a short half-life time. In this article, we pay attention to the current analytical problems related to the detection of NPS

Application of metabolomics in toxicological analysis

The aim of this article was to present the most important aspects of the modern application of metabolomics in toxicology. The information contained herein comes from works that have appeared in recent years in specialist periodicals and publications devoted to the discussed issue. The first part of the work describes what metabolomics is, what is its main area of interest and why it stands out from other sciences ”omics”. Two strategies in metabolomics research were then described: targeted, which is characterized by the quantification and qualitative determination of a specific, selected pool of 50 to 500 metabolites, and non-targeted, which measures all metabolites present in the sample, which is referred to as the "metabolomic fingerprint". The course of a standard metabolome analysis is also presented, with an emphasis on the techniques of sample preparation and analyte determination, as well as the proper selection of the method for the tested material. The following part of the article discusses selected studies related to the use of metabolomics in the diagnosis of drug use and in the assessment of drug toxicity. Experiences related to new biomarkers, such as γ-hydroxy butyric acid (GHB) metabolites, which can extend the diagnostic window of this substance, and compounds whose absence in the urine indicates adulteration and manipulation of this material are discussed. The efforts of scientists in the development of a predictive model enabling the prediction of pharmacological profiles of new psychoactive substances (NPS), as well as research to deepen the knowledge of the metabolism and pathological effects of psychoactive substances, including cocaine and methamphetamine, were pointed out. The final part of the work is devoted to the use of thanatometabolomics in forensic post mortem toxicological analysis and the latest reports describing attempts to use metabolomics in computer-aided toxicological predictive analysis. This review highlights new application opportunities for metabolomics and its current struggles with practical application in the field

Advantages of the zebrafish (Danio rerio) model in solving contemporary problems of neurotoxicity, teratotoxicity and genotoxicity of xenobiotics

The zebrafish (Danio rerio), a small fish belonging to the Cyprinidae family, is one of the most popular animal models used in laboratory studies, including toxicology. It has many beneficial features, such as transparent body structure, easy and economical breeding, a large number of offspring and a short life cycle. In addition, the genome of the zebrafish shows a high homology to the human genome, which makes this fish an attractive research model. The article points to the contemporary challenges of toxicology in terms of neurotoxicity, teratotoxicity and genotoxicity, which can be analysed based on the results of studies carried out on the zebrafish model. The dynamic implementation of new factors, such as nanoparticles, e-cigarettes, new generations of cosmetics or a wide range of chemical enhancers into human living and working environments, can have serious consequences for the health of the general population and the ecosystem as a whole. The work presents the latest research results regarding, among others, neurotoxic effects of ethanol, teratotoxic and neurotoxic effects of e-cigarettes, teratotoxic, neurotoxic and genotoxic effects of selected nanoparticles and microplastics assessed in experiments using the zebrafish model. The characteristics of the micronucleus test and the comet test are also presented as the most frequently chosen methods for assessing the genotoxic effect of xenobiotics in studies on the Danio rerio model.The results of the studies underline the need for further analysis and monitoring of the effects of these substances, in particular harmful effects on living organisms, and for remedial measures to protect the environment. As we have tried to demonstrate in this article, one of the very convenient possibilities in this respect is the use of the striped zebrafish model. A particularly valuable premise in assessing the genotoxic effects of xenobiotics in this case is the above-mentioned high homology of the Danio rerio and human genomes

Wide-field magnetometry using nitrogen-vacancy color centers with randomly oriented micro-diamonds

Magnetometry with nitrogen-vacancy (NV) color centers in diamond has gained significant interest among researchers in recent years. Absolute knowledge of the three-dimensional orientation of the magnetic field is necessary for many applications. Conventional magnetometry measurements are usually performed with NV ensembles in a bulk diamond with a thin NV layer or a scanning probe in the form of a diamond tip, which requires a smooth sample surface and proximity of the probing device, often limiting the sensing capabilities. Our approach is to use micro- and nano-diamonds for wide-field detection and mapping of the magnetic field. In this study, we show that NV color centers in randomly oriented submicrometer-sized diamond powder deposited in a thin layer on a planar surface can be used to detect the magnetic field. Our work can be extended to irregular surfaces, which shows a promising path for nanodiamond-based photonic sensors

Markers of antioxidant defense in patients with type 2 diabetes

Aims. Diabetes is considered a state of increased oxidative stress. This study evaluates blood concentrations of selected markers of antioxidant defense in patients with type 2 diabetes. Methods. The study included 80 type 2 diabetes patients and 79 apparently healthy controls. Measured markers included ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamyltransferase (GGT) and uric acid serum, and plasma and/or hemolysate levels. Results. FRAP, uric acid, CRP, and GGT levels were significantly higher in patients with diabetes. Plasma and hemolysate GR was significantly higher whereas GPx activity was significantly lower in patients with diabetes. There were no significant differences in antioxidant defense markers between patients with and without chronic diabetes complications. Fasting serum glucose correlated with plasma GPx, plasma and hemolysate GR, FRAP, and serum GGT, and HbA1c correlated with serum GGT. Only FRAP and serum uric acid were significantly higher in obese (BMI>30 kg/m2) patients with diabetes than in nonobese patients. Conclusions. Some components of antioxidant defense such as GR, uric acid, and GGT are increased in patients with type 2 diabetes. However, the whole system cannot compensate for an enhanced production of ROS as reflected by the trend toward decreased erythrocytes GSH

Optical magnetometry based on nanodiamonds with nitrogen-vacancy color centers

Nitrogen-vacancy color centers in diamond are a very promising medium for many sensing applications such as magnetometry and thermometry. In this work, we study nanodiamonds deposited from a suspension onto glass substrates. Fluorescence and optically detected magnetic resonance spectra recorded with the dried-out nanodiamond ensembles are presented and a suitable scheme for tracking the magnetic-field value using a continuous poly-crystalline spectrum is introduced. Lastly, we demonstrate a remote-sensing capability of the high-numerical-aperture imaging fiber bundle with nanodiamonds deposited on its end facet

Rehabilitation after surgical treatment of retrobulbar tumors

The authors propose a set of rehabilitation exercises concerning the muscles which are responsible for movement of the eyeball. After surgical treatments of retrobulbar tumors, the function of the eyeball muscles is often inadequate. Some compensation should be created at the level of the central nervous system, which means trigging adaptation, substitution and habituation. The exercises should be started just after the patient is awakened: first in the horizontal position, then sitting position and finally standing position. The highest number of exercises should be done in the direction of extreme diplopi