The Role of Serum Neutrophil Gelatinase-associated Lipocalin in the Early Diagnosis of Nephropathy in Patients with Acute Alcohol Poisoning

AIM: In our study, we assessed the possibility of using the serum neutrophil gelatinase-associated lipocalin (NGAL) for the early detection of kidney damage in patients with acute alcohol poisoning (AAP). METHODS: The study included 89 patients and 30 healthy donors. All participants in the study were mostly represented by men (90%) aged between 20 and 40 years. The influence of alcohol poisoning severity was also taken into account in the study. The Human NGAL ELISA Kit was used for the quantitative detection of serum NGAL. We also evaluated the main laboratory indicators of kidney functions, including eGFR (calculated according to serum creatinine). RESULTS: We did not find a correlation between blood alcohol concentration and serum NGAL level; also, alcohol poisoning severity did not affect the NGAL values. The results of our study showed the possibility of using the serum NGAL in patients with AAP to detect the preclinical stage of reduced renal function, until the moment when it can be diagnosed with using only serum creatinine. CONCLUSION: We propose to consider an increase in eGFR together with an increase in serum NGAL in this group of patients as a stage, preceding nephropathy, even in the absence of clinical and laboratory signs of impaired renal function

Химико-токсикологическая диагностика острых отравлений феназепамом

Background. The relative availability of Phenazepam makes it a frequent cause of overdose, suicide and non-medical use. At the same time, it remains insufficiently studied in chemical and toxicological terms.The aim of study. to create an accessible, rapid method for detecting Phenazepam in biological matrices of patients with acute poisoning.Materials and methods. We used thin-layer chromatography (TLC), gas chromatography with a mass selective detector (GC-MS), high performance liquid chromatography with a tandem mass-selective detector (LC-MS/MS) and immunochromatographic analysis (ICA). The preparation of samples of intact urine with the addition of standard solutions of Phenazepam and real urine samples of patients with acute poisoning with Phenazepam was carried out using liquid-liquid extraction or precipitation of related components of the sample with acetonitrile. Hydrolysis and derivatization were also added in GC-MS analysis.Results. The analysis of statistics of the Department of Acute Poisonings of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2014-2016 showed that Phenazepam poisonings averaged 9.2% of the total number of admissions and mainly occurred as suicidal attempts. A technique has been developed for the detection of Phenazepam by TLC, which gives more objective results than ICA. For confirmatory analysis, it is advisable to use LC-MS/MS method for the native substance and GC-MS for the products of hydrolysis after derivatization. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment, difficult sample preparation, and makes it possible to reliably detect toxic and lethal concentrations of Phenazepam.Актуальность. Относительная доступность феназепама делает его частой причиной передозировок, суицидов и немедицинского использования. В то же время он остается недостаточно изученным в химикотоксикологическом отношении. ЦЕЛЬ ИССЛЕДОВАНИЯ Создание доступной экспрессной методики обнаружения феназепама в биологических средах пациентов с острым отравлением им.Материал и методы. Использовали методы тонкослойной хроматографии (ТСХ), газовой хроматографии с масс-спектрометрическим детектированием (ГХ-МС), высокоэффективной жидкостной хроматографии с тандемным масс-спектрометрическим детектированием (ВЭЖХ-МС/МС), иммунохроматографический анализ (ИХА). Пробоподготовка образцов интактной мочи с добавлением стандартных растворов феназепама и реальных образцов мочи пациентов с острыми отравлениями феназепамом проводилась методами жидкость-жидкостной экстракции или осаждения сопутствующих компонентов пробы ацетонитрилом, а также добавляли стадии гидролиза и дериватизации при анализе методом ГХ-МС.Результаты. Анализ статистики отделения острых отравлений НИИ скорой помощи им. Н.В. Склифосовского за 2014–2016 гг. показал, что отравления феназепамом составляют в среднем 9,2% от всего числа поступлений и совершаются преимущественно с суицидальной целью. Разработана методика обнаружения феназепама методом ТСХ, которая дает более объективные результаты, чем ИХА. Для подтверждающего анализа целесообразно использовать метод ВЭЖХ-МС/МС по нативному веществу и ГХ-МС по продуктам гидролиза после дериватизации. По сравнению с подтверждающими методами разработанная методика ТСХ-скрининга обладает экспрессностью, не требует использования дорогостоящего высокотехнологичного оборудования, трудоемкой пробоподготовки, позволяет достоверно выявлять феназепам в моче с концентрацией свыше 1 мкг/мл (предел обнаружения методики)

Chemical and Toxicological Diagnosis of Acute Poisonings with Phenazepam

Background. The relative availability of Phenazepam makes it a frequent cause of overdose, suicide and non-medical use. At the same time, it remains insufficiently studied in chemical and toxicological terms.The aim of study. to create an accessible, rapid method for detecting Phenazepam in biological matrices of patients with acute poisoning.Materials and methods. We used thin-layer chromatography (TLC), gas chromatography with a mass selective detector (GC-MS), high performance liquid chromatography with a tandem mass-selective detector (LC-MS/MS) and immunochromatographic analysis (ICA). The preparation of samples of intact urine with the addition of standard solutions of Phenazepam and real urine samples of patients with acute poisoning with Phenazepam was carried out using liquid-liquid extraction or precipitation of related components of the sample with acetonitrile. Hydrolysis and derivatization were also added in GC-MS analysis.Results. The analysis of statistics of the Department of Acute Poisonings of the N.V. Sklifosovsky Research Institute for Emergency Medicine in 2014-2016 showed that Phenazepam poisonings averaged 9.2% of the total number of admissions and mainly occurred as suicidal attempts. A technique has been developed for the detection of Phenazepam by TLC, which gives more objective results than ICA. For confirmatory analysis, it is advisable to use LC-MS/MS method for the native substance and GC-MS for the products of hydrolysis after derivatization. Compared to confirmatory methods, the developed TLC-screening technique is expressive, does not require the use of expensive high-tech equipment, difficult sample preparation, and makes it possible to reliably detect toxic and lethal concentrations of Phenazepam

Effects of an Impeller Rim and Radial Clearance on Energy Characteristics of an Axial Pump

The results of numerical and experimental research conducted in the Laboratory for Hydraulic Machinery Construction of Peter the Great St. Petersburg Polytechnic University are presented. The research is aimed at studying the effects of an impeller radial clearance and rim on the energy characteristic of low-pressure axial pumps of the specific speed ns≈600. It is shown that these design features of a flow duct have significant effects on stage parameters, and they have to be accounted for when verifying design and experimental characteristics of axial pumps

The carboxy-terminal coiled-coil of the RNA polymerase β′-subunit is the main binding site for Gre factors

Bacterial Gre transcript cleavage factors stimulate the intrinsic endonucleolytic activity of RNA polymerase (RNAP) to rescue stalled transcription complexes. They bind to RNAP and extend their coiled-coil (CC) domains to the catalytic centre through the secondary channel. Three existing models for the Gre–RNAP complex postulate congruent mechanisms of Gre-assisted catalysis, while offering conflicting views of the Gre–RNAP interactions. Here, we report the GreB structure of Escherichia coli. The GreB monomers form a triangle with the tip of the amino-terminal CC of one molecule trapped within the hydrophobic cavity of the carboxy-terminal domain of a second molecule. This arrangement suggests an analogous model for recruitment to RNAP. Indeed, the β′-subunit CC located at the rim of the secondary channel has conserved hydrophobic residues at its tip. We show that substitutions of these residues and those in the GreB C-terminal domain cavity confer defects in GreB activity and binding to RNAP, and present a plausible model for the RNAP–GreB complex

Crystallization and preliminary crystallographic analysis of the transcriptional regulator RfaH from Escherichia coli and its complex with ops DNA

The E. coli transcriptional regulator RfaH was cloned, expressed, purified and crystallized and the complex of RfaH with its target DNA oligonucleotide was cocrystallized. Complete diffraction data sets were collected for the apo protein and its nucleic acid complex at 2.4 and at 1.6 Å resolution, respectively