Физико-химические основы экстракционного выделения палладия из солянокислых растворов оксиоксимами и их смесями

The extraction of Pd(II) from solution HCl by hydroxyoxime 5-(1,1,3,3- tetrametylbutyl)-2- hydroxybenzylphenyloxime (ABP) and mixture of hydroxyoximes with kerosene has been studied. The technological schema of Pd extraction from solution HCl with use of ABP has been suggested. The extraction metod of Pd by mixture of 1015% 5-nonyl-2-hydroxybenzylloxim (Аcorga P-50) + 57% trioctylamin (ТОА) + 810% isooctanol, with high yield in wide diaposons of acidity has been suggestedИсследована экстракция Pd(II) и сопутствующих элементов из растворов HCl 5-(1,1,3,3-тетра- метилбутил)-2-оксибензофеноноксимом (АБФ) и смесями, содержащими оксиоксимы в керосине. Предложена технологическая схема селективного извлечения Pd из растворов HCl с использованием АБФ

ОБРАЗОВАНИЕ КОМПЛЕКСОВ МЕДИ(II) С ВОДОРАСТВОРИМЫМ β-ФУРФУРОЛОКСИМОМ

The paper is devoted to the interaction of copper(II) chloride with water soluble β-furfuraldoxime (N-(furan-2-ylmethyliden)hydroxylamine) in hydrochloric solutions. It was been revealed that the degree of copper(II) precipitation from aqueous solutions and hydrochloric solutions with the pH of 4 M HCl by this reagent is not higher than 52% even when the precipitant is used in abundance. These dependencies has been compared to the similar results of palladium(II) precipitation obtained when all other conditions were equal. It has been discovered that various complexes are formed when Cu(II) reacts with a β-furfuraldoxime and that it depends on the acidity of the solution. In weak acid solutions (0.01-0.1 M HCl) the «green» complex of composition [CuL4Cl2] was obtained and in this complex the oxime is coordinated with the central atom by an oxygen atom of the oxime group. The so-called «red» complex of composition [CuL2Cl2] is formed in the pH range of 1-4 M HCl and in ethanol. In this complex the coordination of ligand molecules is realized by the oxygen atom of the furan ring and by the oxygen of the oxime group. Reagent N-(furan-2-ylmethyliden)hydroxylamine can be used for practical quantitative release of palladium from hydrochloric solutions. However, it does not provide the separation of copper and palladium in their joint presence.В работе изучено взаимодействие хлорида меди(II) с водорастворимым β-фурфуролоксимом (N-(фуран-2-илметилиден)гидроксиламином) в солянокислых растворах. Выявлено, что степень осаждения меди(II) данным реагентом из водных растворов и до достижения кислотности 4 М HCl не превышает 52% даже при использовании избытка осадителя. Полученные зависимости сопоставлены с аналогичными данными для осаждения палладия(II) при прочих равных условиях. Установлено, что при взаимодействии Cu(II) с β-фурфуролоксимом в слабокислых растворах (0.01-0.1 М HCl) получается «зеленый» комплекс состава [CuL4Cl2], в котором оксим координируется к центральному атому через атом кислорода оксимной группы. В диапазоне кислотности 1-4 М HCl, а также в среде этилового спирта происходит образование так называемого «красного» комплекса состава [CuL2Cl2], в котором координация молекул лиганда осуществляется через атом кислорода фуранового кольца и кислорода оксимной группы. Реагент N-(фуран-2-илметилиден)-гидроксиламин может быть использован для практически количественного выделения палладия из солянокислых растворов, однако он не обеспечивает разделения меди и палладия при их совместном присутствии

Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins

Chronic hepatitis B is a severe liver disease associated with persistent infection with hepatitis B virus. According to recent estimations, 250 million people in the world are chronically infected, including 3 million chronically infected people in Russia. Antiviral therapeutics (nucleos(t)ide analogues and PEGylated interferon) suppress viral transcription and replication, but do not eliminate the virus from infected cells. The key reason for HBV persistency is a stable form of the viral genome (covalently closed circular DNA, cccDNA) that exists as a minichromosome protected from novel cccDNA-targeting therapeutics. Novel therapeutic approaches aimed at elimination or inactivation of cccDNA are urgently needed. CRISPR/Cas9 systems induce double strand breaks in target sites of DNA sequences. Experiments with CRISPR/Cas9 demonstrated high antiviral activity and efficient cleavage of cccDNA, but a small part of cccDNA pool remains intact. One of the main reasons of incomplete cccDNA elimination might be the structural organization of cccDNA, which persists in a heterochromatinized, very compacted form and is not be accessible to CRISPR/Cas9 systems. Viral protein HBx unwinds cccDNA and regulates cccDNA epigenetically by recruiting transcription-remodeling factors. In this work, we analyzed effects of CRISPR/Cas9 in combination with an HBxencoding plasmid or plasmids encoding mutant forms of HBx (HBxMut, which does not interact with pro-apoptotic factors Bcl-2 и Bcl-xL, and HBxNesm is localized exclusively in the nucleus and does not generate reactive oxygen species and double strand breaks in the genome). We showed that HBx improves CRISPR/Cas9 efficiency, decreasing pregenomic RNA transcription level over 98%. Moreover, we analyzed optimal ratios of plasmids encoding CRISPR/ Cas9 and HBx proteins for better antiviral efficacy. Furthermore, we discovered that HBx proteins do not have an effect on proliferation and viability of the transfected cells. In conclusion, CRISPR/Cas9 with HBx proteins exhibit high antiviral effect

Favorable Outcome of Severe Acute Methadone Poisoning (Clinical Case)

Purpose: to contribute to relief of metabolic disorders associated with hypoxia by including a succinate correcting tissue metabolism into the scheme of intensive care of acute severe methadone poisoning complicated by the crush syndrome.Materials and methods. We examined the dynamics of clinical manifestation of acute methadone poisoning complicated by crush syndrome: changes in clinical and biochemical parameters, coagulation test findings, blood gas composition and acid-base state, ECG and X-ray findings.Results. By the 7th day after patient's admission in the ICU, stabilization of hemodynamics, recovery of spontaneous breathing and consciousness, reduction of swelling and the beginning of the formation of pressure ulcers were observed; on the 8 the day, restoration of urination and characteristics of urine were registered. On the 12th day, the patient was transferred to the toxicology unit being in a state of moderate severity and demonstrating positive changes in all clinical parameters.Conclusion. The inclusion of a drug with antioxidant/antihypoxant properties in the infusion therapy scheme allows to relieve metabolic disorders associated with hypoxia, and thereby increase the effectiveness of treatment: i.e. to relief clinical and laboratory manifestations and reduce the ICU stay

The structure of the oropharyngeal genus Candida fungi community in HIVinfected patients

At the present time virtually no data are available about the structure of the genus Candida fungus able to target HIV-infected patients and serve as an etiological factor of candidiasis. The aforementioned shaped the aim of the study: to examine structure of the Candida genus community colonizing the oropharynx in HIV-infected patients with clinical manifestations of oropharyngeal candidiasis. There was conducted a microbiological study of the oropharynx in 31 HIV-infected patients (51.6% males and 48.4% females) with clinical manifestations of oropharyngeal candidiasis treated at Moscow Infectious Clinic No. 2 inpatient department in the years 2015–2017. We confirmed the diversity of the oropharyngeal Candida spp. community found in HIV-infected patients. Total 52 isolates of the genus Candida were isolated. C. albicans dominated in 57.7% cases, whereas C. glabrata prevailed (21.1%) among non-albicans species. Minor components were represented by C. tropicalis (11.5%) and C. krusei (9.6%). C. albicans and C. glabrata were sensitive to polyenes, whereas minor community components — to itroconazole and clotrimazole. The vast majority of fungal strains were resistant to fluconazole. The genus Candida community reveals a unique architecture so that any member may exist in the oropharyngeal biotope of HIV-infected patients as a monoculture or in association: homogeneous, consisting of a single species strains, or heterogeneous, formed by several species. Candida fungi in 18 patients (58.1%) were isolated as a monoculture, whereas in 13 (41.9%) subjects — in association consisting of 34 isolates (65.4% of total number), of which 16 (30.8%) and 18 (34.6%) were isolated from homogeneous and heterogeneous associations, respectively. There were identified 9 two-component associations (69.2%), and 4 (30.8%) consisting of three or more components. It turned out that pattern of the examined community was mainly determined by species composition that agrees with previous data. Most common associations were presented by C. krusei (100%) and C. albicans (73.3%). Upon that, most often C. albicans (72.7%) formed a homogeneous type of associations. Sensitivity of Candida fungi to antimycotic drugs also depended on the architecture of related community. C. albicans isolates in heterogeneous associations revealed a wide range of resistance acquired by contact with non-albicans species

The association between <i>Candida albicans</i> sensitivity to antimycotic drugs and the architecture of their microbial community in the oropharynx of HIV infected patients

Relevance. Candida infection remains relevant due to the wide spread of antimycotic-resistant strains of Candida fungi, especially among immunocompromised individuals. It was previously discovered that the Candida spp. microbial community in the biotope of the oropharynx of HIV infected patients is characterized by a certain architecture: they can be present in this biotope in the form of a monoculture or as association of co-isolates. It has been suggested that the architecture of the Candida microbial community may influence their resistance to antimycotic drugs. Purpose a comparative study of the association between the architecture of the C. albicans microbial community in the oropharynx of HIV infected patients with oropharyngeal candidiasis and their sensitivity to antimycotic drugs. Materials and methods. A microbiological study of 52 isolates of Candida fungi (C. albicans, C. glabrata, C. tropicalis and C. krusei) from the oropharynx of 31 HIV infected patients with clinical manifestations of oropharyngeal candidiasis aged 20 to 69 years with almost equal gender distribution was carried out. In the form of monocultures, 18 isolates were isolated, while 34 were identified as co-isolates, which formed 16 homogeneous communities that included strains of the same species, and 18 heterogeneous ones that consisted of fungi of various species. Results. It was found that heterogeneous communities of C. albicans were markedly distinguished by sensitivity to antimycotic drugs, in particular, by low sensitivity to imidazoles. Homogeneous communities practically did not differ from monocultural ones. The general properties of the C. non-albicans population were largely similar to those of C. albicans, but were characterized by lower heterogeneity in response to antimycotic drugs. Conclusion. The architecture of the community of C. albicans isolated from the oropharynx of HIV infected patients with clinical manifestations of oropharyngeal candidiasis affects their sensitivity to antimycotic drugs. When selecting effective antimycotic therapy for such patients, it is necessary to take into account the structure of the Candida spp. community in the oropharynx

Hepatitis B virus and site-specific nucleases: effects of genetic modifications in CRISPR/Cas9 on antiviral activity

Chronic hepatitis B is a severe liver disease caused by persistent infection of hepatitis B virus in human hepatocytes. Chronic hepatitis B is one of the most common diseases in the world. According to recent estimations, more than 250 million people are chronically infected and more than 1 million of people die annually due to consequences of chronic hepatitis B: liver cirrhosis and hepatocellular carcinoma. The key factor of hepatitis B virus persistency is a special form of viral genome called circular covalently closed DNA. Current therapeutics suppress viral replication but have no effect on circular covalently closed DNA as it exists in the nuclei of hepatocytes as a minichromosome and is not accessible for therapeutics. Commonly, viral reactivation occurs after cessation of treatment. Therefore, duration of antiviral treatment is supposed to be indefinitely long. One of the most promising approaches to target circular covalently closed DNA is the technology of site-specific nucleases CRISPR/Cas9 from Streptococcus pyogenes. A short guide RNA recruits an SpCas9 protein to the viral genome and induces generation of DNA double strand breaks. However, there are several limitations of CRISPR/Cas9 hampering translation of this technology into the clinic. First, efficacy of CRISPR/Cas9 needs to be improved. Second, CRISPR/Cas9-mediated off-target mutagenesis represents a menacing problem which has to be addressed. To overcome these limitations, several approaches have been devised to improve CRISPR/Cas9 activity (modification of guide RNAs) and reduce off-target mutagenesis (a Cas9 protein with enhanced specificity, eSpCas9). In this study, we compared antiviral activity of a classic SpCas9 with an eSpCas9 system as well as analyzed effects of gRNAs modification on anti-HBV effects. Here, we demonstrated that SpCas9 has the highest antiviral potency, reducing transcription and replication of HBV over 90%. Hepatitis B virus covalently closed circular DNA declined over 90% post CRISPR/Cas9 transfection. Although it was previously shown that modified guide RNAs increase nucleolytic activity of CRISPR/Cas9, our results indicated that this modification impairs antiviral activity of CRISPR/Cas9. To conclude, CRISPR/Cas9 effectively suppress viral replication and transcription per se. Described modifications do not potentiate antiviral activity of CRISPR/Cas9 system and should not be used for development of future therapeutics. The best strategy to improve CRISPR/Cas9 efficacy is to design new highly effective guide RNAs

Потенциальные предикторы тяжелого течения и исхода внебольничной пневмонии

Severe pneumonia is a condition with a high risk of death and mandatory hospitalization in the intensive care unit. The incidence of severe pneumonia has increased dramatically during the pandemic of new coronavirus infection. Timely diagnosis and early initiation of adequate treatment of severe pneumonia are crucial for improving survival of critically ill patients.The aim of this review was to analyze published scientific research on molecular markers that allow to objectively assess the severity of pneumonia and to determine treatment tactics based on the predicted outcome upon admission to the hospital. A systematic search was conducted in the electronic databases PubMed, Medline, Web of Science for the period 2019 - 2022.Conclusion. The review focuses on the prognostic role of a number of markers of immune response, vascular transformation, as well as angiotensin II and angiotensin converting enzyme-2. Further prospective studies of potential predictors of severe pneumonia will enable using marker molecules in a comprehensive clinical and laboratory diagnosis for early prediction of the hospitalized patient’s condition and expected outcome.Тяжелая пневмония (ТП) — состояние, при котором отмечается высокий риск летального исхода, а госпитализация в отделение интенсивной терапии является обязательной. Заболеваемость ТП резко возросла в период пандемии новой коронавирусной инфекции. Своевременная диагностика и раннее начало адекватного лечения ТП имеют решающее значение для повышения выживаемости тяжелобольных пациентов.Целью обзора явился анализ научных публикаций, посвященных изучению молекулярных маркеров, позволяющих уже при поступлении в стационар объективно оценить степень тяжести пневмонии и определить тактику лечения, основываясь на прогнозе возможного исхода заболевания. Систематический поиск проведен в электронных базах данных PubMed, Medline, Web of Science за 2019—2022 гг.Заключение. В обзоре внимание уделено прогностической роли ряда маркеров иммунного ответа организма, сосудистой трансформации, а также ангиотензина II и ангиотензинпревращающего фермента-2. Дальнейшие проспективные исследования потенциальных предикторов течения ТП позволят включить определение молекул-маркеров в комплексную клинико-лабораторную диагностику с целью раннего прогнозирования состояния госпитализируемого пациента и предполагаемого исхода

Predictors of thromboembolic complications in patients with severe SARS-CoV-2 coronavirus infection

Aim. To identify predictors of the development of thromboembolic complications (TECs) in patients with severe SARS-CoV-2 coronavirus infection. Materials and methods. A single-center observational retrospective study included 1634 patients with a confirmed diagnosis of SARS-CoV-2 coronavirus infection. The patients were divided into 2 groups depending on the availability of the feasibility study. The criterion for inclusion of patients in the main group was the presence of venous feasibility studies in 127 patients (group I), the comparison group consisted of 1507 patients in whom the course of COVID-19 was not complicated by the development of feasibility studies (group II). Results. When performing computed tomography of the chest organs, it was revealed that patients with a feasibility study had a higher percentage of lung tissue damage than patients in the comparison group: 55% [37.5; 67.5] and 37.5% [25.0; 47.5], respectively (p0.001). The average values of C-reactive protein in I patients group were 129 [60.1; 211] ng/l, which was significantly higher than in II patients group – 41.0 [12.2; 97.6] ng/l (p0.001), interleukin-6 – 176 [52.9; 471] pg/ml and 39.4 [11.0; 107] pg/ml (p0.001), respectively. A one-factor regression analysis proved a significant contribution of comorbid pathology to the development of feasibility studies in patients with COVID-19. The presence of three nosologies at the same time: arterial hypertension, coronary heart disease (CHD) and chronic kidney disease increased the probability of a feasibility study by 4.81 times (odds ratio 4.8117, 95% confidence interval 3.2064–7.2207), in patients with arterial hypertension, CHD, chronic kidney disease and type 2 diabetes – by 5.63 times (odds ratio 5.6321, 95% confidence interval 3.1870–9.9531). Conclusion. The presence of severe comorbid pathology significantly increased the risk of developing a feasibility study in patients with COVID-19. The most significant predictors of the development of feasibility studies in patients with severe SARS-CoV-2 coronavirus infection. They are: CHD, arterial hypertension and type 2 diabetes