Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology

In the twenty-first century, metabolomics allowed evaluating the profile of metabolites of various classes of compounds in the human body. The most important achievement of the metabolic approach is to obtain evidence of the intersection of human biochemical pathways and its microbiota. The effect of certain microbial metabolites on the work of key enzymes involved in the biotransformation of amino acids and other substances becomes more important in patients at risk of developing neurological and mental disorders and also contributes to the development of life-threatening conditions up to multiple organ failure after operations, injuries, and serious diseases. The authors of this chapter call the microbiota an “invisible organ,” emphasizing its functional significance, and not just taxonomy, as previously thought. This chapter will discuss the mutually beneficial integration of the metabolome/microbiome in the body of healthy people and will focus on the effects of microbiota dysfunction

Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases

Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice

Three-year survival rate and changes in the level of consciousness in outpatients after severe brain injuries

Introduction. There is a worldwide lack of statistical data about the patients with chronic disorders of consciousness (DOC). In Russia, there are no such data at all. Objective: to perform the first study in Russia to assess the survival rate and changes in the level of consciousness in outpatients with the chronic DOC after their hospital discharge as well as to identify the predictors of survival and improvement in the level of consciousness. Materials and methods. All the participants (n = 142) underwent their treatment and rehabilitation in Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology from January 2016 to January 2020. We recorded the changes in patient's vital status and their level of consciousness at the endpoints of 3, 6, 12, 24, and 36 months from the brain injury (both for hospital and outpatient stages). We used the KaplanMeier method to assess the survival rate. We also used the logistic regression model to determine the correlation between the predictors of the survival and the improvement in the level of consciousness at baseline and 36 months after the injury. Results. The mortality rate in the study group 3 years after the brain injury was 86.6%. Regardless of the survival rate, the level of consciousness had significantly improved (i.e., they regained communication) in 22.5% of patients within 3 years after the index event. The statistically significant final model of the regression analysis (for 142 patients) showed that younger age and higher overall CRS-R score improved the survival rate. The logistic regression model used to determine the predictors of the improvement in the level of consciousness among the survivors gave no significant results. Conclusions. High mortality rate among the outpatients, whose level of consciousness had improved at discharge, proves the ineffectiveness of the outpatient rehabilitation. Thus, we need to find a way to improve it. The authors hope that the data obtained in this study will form the basis of their research

Дефекты мембран эритроцитов у пациентов с нарушениями функции головного мозга (пилотное исследование)

The aim of the paper: to identify promising diagnostic and prognostic biomarkers of pathological processes development based on the red blood cell membrane morphology and nanostructure in patients with brain disorders in the Intensive Care Unit.Materials and methods. The study included 24 patients from the anesthesiology and resuscitation ward of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology. Blood was acquired from the patients for standard tests, and all further tests were performed in vitro. The images of red blood cells were obtained using the atomic force microscope «NTEGRA Рrima» (NT-MDT, Russia) in semi-contact mode.Results. Patients from the anesthesiology and intensive care ward with traumatic brain injury, ischemic and hemorrhagic stroke, cerebral edema, and post-hypoxic encephalopathy had different blood cell shapes and localized defects of different topology on the surface of erythrocyte membranes including defects of pallor, torus, and nanostructure.Conclusion. In this pilot study we have shown that several defects represent the trigger mechanisms for the development of a total membrane damage. Local topographic defects of nanostructures and abnormalities of erythrocyte morphology are irreversible. The number and quality of these abnormalities may eventually be used as a diagnostic and prognostic biomarker of pathological processes.Цель работы. Выявление перспективных диагностических и прогностических биомаркеров развития патологических процессов на основе особенностей морфологии и наноструктуры мембран эритроцитов у пациентов с нарушениями функции головного мозга, находящихся в отделении анестезиологии и реанимации.Материалы и методы. В исследование включили 24 пациента отделения анестезиологии и реанимации ФНКЦ РР. Кровь забирали у данных пациентов для стандартных анализов, и все дальнейшие исследования проводили in vitro. Изображения эритроцитов получали с помощью атомного силового микроскопа «NTEGRA Рrima» (NT-MDT, Россия) в полуконтактном режиме.Результаты. У пациентов отделения анестезиологии и реанимации с черепно-мозговой травмой, ишемическим и геморрагическим инсультом, отеком головного мозга, постгипоксической энцефалопатией имели место различные формы клеток крови, на поверхности мембраны эритроцитов возникали локальные дефекты различной топологии: дефекты пэллора, тора, наноструктуры.Заключение. В данном пилотном исследовании мы показали, что ряд дефектов являются стартовым механизмов развития тотальных повреждений мембран. Локальные топографические дефекты наноструктур, а также нарушения морфологии эритроцитов необратимы. Количество и качество этих нарушений в перспективе могут быть использованы как диагностический и прогностический биомаркер патологических процессов

An immunoregulatory role of dendritic cell-derived exosomes versus HIV-1 infection : take it easy but be warned

Dendritic cells (DCs) are professional antigen-presenting cells capable to initiate and then drive T cell responses. Naturally, DCs sense various pathogens and their products in order to present those to immune cells and in turn initiate immune reaction. In a case of wounding, DCs recognize products released by damaged cells and then contribute to the induction of inflammation associated with further clearance of necrotic and apoptotic cells (1). In addition to DC subtypes that initiate inflammatory reaction, there are DC subsets, which exert tolerogenic properties directed to dampen extensive inflammation and promote switching to wound healing

Atherosclerosis in HIV Patients: What Do We Know so Far?

For the past several decades, humanity has been dealing with HIV. This disease is one of the biggest global health problems. Fortunately, modern antiretroviral therapy allows patients to manage the disease, improving their quality of life and their life expectancy. In addition, the use of these drugs makes it possible to reduce the risk of transmission of the virus to almost zero. Atherosclerosis is another serious pathology that leads to severe health problems, including disability and, often, the death of the patient. An effective treatment for atherosclerosis has not yet been developed. Both types of immune response, innate and adaptive, are important components of the pathogenesis of this disease. In this regard, the peculiarities of the development of atherosclerosis in HIV carriers are of particular scientific interest. In this review, we have tried to summarize the data on atherosclerosis and its development in HIV carriers. We also looked at the classic therapeutic methods and their features concerning the concomitant diagnosis

Is insulin pro-atherogenic at the cellular level?

Aim: This study was undertaken to test the hypothesis that insulin treatment has unexpected pro-atherogenic effects at the cellular level, namely, proliferative activity and intracellular cholesterol content.Methods: Primary cultures of subendothelial cells derived from non-atherosclerotic human aorta and mouse peritoneal macrophages were used to investigate the in vitro effect of insulin on atherosclerosis-related parameters, such as cellular cholesterol content and proliferation rate. Additionally, the effect of insulin treatment in 33 type 1 diabetic patients on serum atherogenicity (i.e. its ability to induce cholesterol accumulation in cultured cells) was investigated.Results: Insulin (1-1,000 µU/mL) did not affect [3H]-thymidine incorporation or cholesterol content in either type of cultured cell. Most blood sera obtained from type 1 diabetic patients induced a 1.5- to 1.7-fold increase in cholesterol content of cultured cells, but this effect did not correlate with serum insulin levels. Exogenous insulin added to cultured cells did not modify the effect of patient's sera on cholesterol level and proliferation of cultured cells.Conclusion: The results suggest that insulin does not exert direct atherogenic actions at the level of arterial cells, with the respect to proliferative activity and cholesterol content