Репозиторий Университета

© 2021 Introduction: Synthetic cannabinoids are abused substances with strong psychoactive effects. Little is known about the effects on neurotransmission and the toxicity of the second-generation cannabinoid 5F-APINAC. The objective was to assess the influence of short- and long-term exposures of 5F-APINAC on metabolites associated with neurotransmission on zebrafish. Methods: Short-term (“acute”, 4 h) and long-term (“chronic”, 96 h) exposures to 5F-APINAC were performed at 0.001, 0.01, 0.1, 1.0 and 10 μM. Intervention groups were compared with a vehicle control. Each group n = 20 zebrafish eggs/larvae. Metabolites related to neurotransmission were determined. Results: In chronic exposure, larvae exposed to 10 μM 5F-APINAC presented morphological and developmental alterations. GABA had the lowest concentrations at higher exposure in acute (p < 0.01) and chronic (p < 0.001) experiments. Glutamine showed a descending trend in the acute experiment, but an ascending trend in the chronic exposure (p < 0.05). In chronic exposure, tryptophan presented an overall descending trend, but with a neat increase at 10 μM 5F-APINAC (p < 0.001). Tryptamine in acute exposure presented lower (p < 0.05) concentrations at higher doses. Dopamine and acetylcholine presented highest (p < 0.05) concentrations in the acute and chronic exposures, but with a drop at the highest doses in the chronic experiments. In chronic exposure, xanthurenic acid decreased, except for the highest dose. Picolinic acid was increased at the highest doses in the chronic experiment (p < 0.001). Conclusions: Short- and long-term exposures induced metabolomic alterations associated with the gamma-aminobutyric acid/glutamic acid, dopaminergic/adrenergic, cholinergic neurotransmitter systems, and the kynurenine pathway. Chronic exposure at 10 μM 5F-APINAC was associated with embryotoxicity confirmed by teratogenesis.

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2020 The Authors The increased diffusion of the so-called novel psychoactive substances (NPS) and their continuous change in structure andconceivably activity has led to the need of a rapid screening method to detect their biological effects as early as possible after their appearance in the market. This problem is very felt in forensic pathology and toxicology, so the preclinical study is fundamental in the approach to clinical and autopsy cases of difficult interpretation intoxication. Zebrafish is a high-throughput suitable model to rapidly hypothesize potential aversive or beneficial effects of novel molecules. In the present study, we measured and compared the behavioral responses to two novel neuroactive drugs, namely APINAC, a new cannabimimetic drug, and methiopropamine (MPA), a methamphetamine-like compound, on zebrafish larvae (ZL) and adult mice. By using an innovative statistical approach (general additive models), it was found that the spontaneous locomotor activity was impaired by the two drugs in both species: the disruption extent varied in a dose-dependent and time-dependent manner. Sensorimotor function was also altered: i) the visual object response was reduced in mice treated with APINAC, whereas it was not after exposure to MPA; ii) the visual placing responses were reduced after treatment with both NPS in mice. Furthermore, the visual motor response detected in ZL showed a reduction after treatment with APINAC during light-dark and dark-light transition. The same pattern was found in the MPA exposed groups only at the dark-light transition, while at the transition from light to dark, the individuals showed an increased response. In conclusion, the present study highlighted the impairment of spontaneous motor and sensorimotor behavior induced by MPA and APINAC administration in both species, thus confirming the usefulness of ZL as a model for a rapid behavioural-based drug screening.

© 2019 American Association of Endodontists Introduction: Pulp stones are mineral structures that develop in the pulp tissue triggered by several clinical conditions. The exact biochemical process behind the occurrence of pulp stones is uncertain. This study aimed to perform a structural and crystallographic characterization of pulp stones and dentin from extracted human teeth. Methods: The sample consisted of 13 erupted and unerupted permanent human teeth diagnosed with pulp stones. The teeth were analyzed with scanning electron microscopy with secondary and backscattered electrons, energy-dispersive spectroscopy, micro-Raman spectroscopy, micro–X-ray diffraction, and inductively coupled plasma atomic emission spectroscopy. Results: The pulp stones revealed a heterogeneous morphology and structure compared with each other. Compared with the adjacent dentin, the pulp stones had a similar structure. From a chemical point of view, oxygen, calcium, carbon, and phosphorus were the most prevalent chemical elements in the inner part of the stones, whereas on the surface carbon, nitrogen, sulfur, chlorine, aluminum, potassium, zinc, copper, and lead were the most prevalent. Copper, iron, and zinc were higher in the stones than the dentin (P < .05). Statistically significant differences between the chemical structure of stones from erupted and unerupted teeth were not detected (P > .05). Conclusions: Pulp stones have structural and chemical properties that are similar to dentin. Variations in morphology are common.

© 2018 Informa UK Limited, trading as Taylor  &  Francis Group Objective: The aim of this case series is to raise awareness of obstetric-related atypical haemolytic uraemic syndrome (aHUS) amongst obstetricians and gynaecologists. Study design: Data from 20 consecutive patients, aged 19–38, with obstetric-aHUS manifestation during or immediately after pregnancy are reported. Patients were diagnosed and treatment was initiated between 2012 and 2016. Results: Presentation of aHUS was mainly preceded by preeclampsia and/or haemolysis, elevated liver enzymes and low platelet count syndrome, other obstetric complications, or by diarrhoea. Thrombotic microangiopathy (TMA) was evident in all patients with signs of microangiopathic haemolysis (sharp decline in haemoglobin; mean 67 g/L), elevated lactate dehydrogenase (LDH; mean 2953.1 U/L), schistocytosis, thrombocytopenia (mean platelet count 52.5 × 109/µL), and acute kidney injury (AKI) (hypercreatininaemia, mean 456.4 µmol/L; oliguria or anuria). The majority of patients (80%) initially presented with arterial hypertension. Diagnosis of obstetric-aHUS was complicated, as multiple organs were affected. Time taken to make the diagnosis of aHUS delayed the initiation of fresh-frozen plasma infusions and plasma exchange (80% of patients) and subsequent eculizumab treatment (40% of patients). Maternal mortality was high (35%) as was foetal mortality (25%). Conclusions: Obstetric-aHUS is a serious condition characterized by multiple organ failure (MOF) and a high mortality rate. Presentation of obstetric-aHUS is preceded by various precipitating factors, suggesting pregnancy complications, and not the pregnancy per se, often induce aHUS in women with a genetic predisposition to its development. A delay in the correct diagnosis and initiation of the most effective treatment can have serious consequences, reinforcing the need to raise awareness of obstetric-aHUS.

© 2018 Dynasty Publishing House. All rights reserved. The article presents a clinical case of severe preeclampsia, HELLP syndrome in a 39-year-old woman, who became pregnant after IVF using donor oocytes. Conclusion: donor egg recipients, irrespective of age, should be viewed as having a higher risk for obstetric complications.

© 2018 Dynasty Publishing House. All rights reserved. Thrombocytopenia (TCP) includes a huge range of diseases and syndromes with different causes and pathogenetic mechanisms. TCP is defined when platelet count less than 150 × 109/L. the Diagnostic search when TCP should begin with the establishment of a pathogenic variant with subsequent verification of the main reasons for TCP. This allows you to select pathogenetic therapy of the disease (glucocorticoids, immunosuppressants, anticoagulants) and to influence the basic process.

© Bionika Media Ltd. Objective. To study the most important aspects of maternal mortality from preeclampsia, eclampsia, the current clinical features of the most severe forms of this complication of pregnancy, as well as main defects in rendering qualified medical care, including those in the development of complications. Subjects and methods. A confidential audit of maternal mortality was conducted in different regions of the Russian Federation in 2013-2015. A total of 270 anonymous copies of primary medical records were analyzed. Results. The features of development and progression of the most severe forms of preeclampsia and eclampsia were identified. The development of preeclampsia in the presence of previous extragenital diseases was seen in most clinical cases. Early clinical manifestation is characteristic in the vast majority of women; and the non-classical (atypical) clinical picture of the disease is also common. Conclusion. Practical activities are proposed, which are aimed at reducing maternal mortality from preeclampsia in Russia.

© 2018 Russian Academy of Sciences. All rights reserved. The current theoretical and experimental data about the impact of the lipid A structure on interactions of lipopolysaccharide (LPS) with serum lipid-binding protein (LBP) are presented. LBP interacts more efficiently with the LPS lipid A from Rhizobium, Escherichia, and Neisseria spp. than with the LPS lipid from Francisella, Porphyromonas, Helicobacter, Chlamydophila, as well as with the lipid A synthetic analogue-compound E5564. It is shown that the lipid A hydrocarbon chain of 14 carbon atoms is most favorable, while that of 16 carbon atoms is ultimate for interaction of LBP with lipid A. A high content of unusually long chains and branched-chain acyl residues in lipid A will further complicate the interaction of LBP with LPS. The reviewed data provide a deeper insight into the mechanisms of the LPS delivery and cell activation accomplished by serum cationic proteins such as LBP. A direct relation between the efficiency of the LBP interaction with a particular lipid A of LPS and the development of the fulminant acute inflammation is proposed.